WO2017003430A1 - Combinaisons moléculaires et à base d'herbes médicinales avec du méthotrexate pour le traitement de maladies et d'affections inflammatoires - Google Patents

Combinaisons moléculaires et à base d'herbes médicinales avec du méthotrexate pour le traitement de maladies et d'affections inflammatoires Download PDF

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WO2017003430A1
WO2017003430A1 PCT/US2015/038341 US2015038341W WO2017003430A1 WO 2017003430 A1 WO2017003430 A1 WO 2017003430A1 US 2015038341 W US2015038341 W US 2015038341W WO 2017003430 A1 WO2017003430 A1 WO 2017003430A1
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huang
grams
sheng
ear
treatment
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PCT/US2015/038341
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Manu Jaggi
Anu Singh
Nadav Shraibom
Eran Steinberg
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Sirba Ltd.
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/655—Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/35—Caprifoliaceae (Honeysuckle family)
    • A61K36/355—Lonicera (honeysuckle)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/708—Rheum (rhubarb)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/80—Scrophulariaceae (Figwort family)
    • A61K36/804—Rehmannia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815—Lycium (desert-thorn)

Definitions

  • the present invention relates generally to disease treatments, including treatments for psoriasis, eczema, melanoma and other skin disorders, inflammatory and autoimmune ailments and cancer. More specifically it concerns the use of combinations of methotrexate and certain herbs, certain herbal extracts and/or certain molecular components of certain herbs with methotrexate, and other
  • antimetabolite and/or antifolate treatments and other known and/or described treatments particularly to treat psoriasis or reduce psoriatic suffering and symptoms, or to treat eczema or blisters, redness or eczematic soreness or itching or crusty skin caused by eczema, or to treat inflammation, or to treat melanoma or to reduce white cell count, tumor size or painfulness from cancer, or to treat or reduce suffering from another skin ailment, or to treat an autoimmune disease or otherwise to treat or to reduce suffering from one or more of diseases causing or stemming from inflammation.
  • Examples include herbal formulas including one of or a combination of two or more of Da Huang, Sheng Di Huang, and Jin Yin Hua, and/or combinations including one or more of Mu Dan Pi, Di Gu Pi, Xian He Cao, and/or Chun Gen Pi., and/or another herb or combination of herbs described herein.
  • Herbal medicines are prevalent, and serve the medicinal needs of a large population around the world.
  • the global herbal medicine market is currently worth around $30 billion.
  • Methotrexate, aminopterin and other antimetabolite, antifolate drugs have been known for treating cancer and autoimmune disorders such as psoriasis. It acts by inhibiting the metabolism of folic acid. Methotrexate is a strong treatment that often causes serious side effects during and after treatment. It is desired to have an herbal and/or molecular combination that may be administered to a patient before, during and/or after a typical treatment regimen to enhance the effectiveness of methotrexate treatments, and/or to reduce side effects of treatment and/or weening from treatment with methotrexate and/or other antimetabolite, antifolate and/or other known and/or described disease treatment. BRIEF DESCRIPTION OF THE DRAWINGS
  • Figure 1 includes a table illustrating an inhibitory effect of a medicinal composition including an herbal combination of Sheng Di Huang, Da Huang and Jin Yin Hua (3HX) and methotrexate (hereinafter in many places "MTX”) in accordance with certain embodiments on proliferation of HaCaT cells.
  • a medicinal composition including an herbal combination of Sheng Di Huang, Da Huang and Jin Yin Hua (3HX) and methotrexate (hereinafter in many places "MTX”) in accordance with certain embodiments on proliferation of HaCaT cells.
  • Figure 2 includes a table illustrating an inhibitory effect of a medicinal composition including an herbal combination of Sheng Di Huang, Da Huang and Jin Yin Hua (hereinafter in many places “3HX”) and betamethasone (hereinafter "BD”) in accordance with certain embodiments on
  • Figures 3A-3B include plots of data illustrating effects of 3HX treatments in accordance with certain embodiments on 12-0-tetradecanoylphorbol- 13 -acetate (hereinafter "TP A”) induced ear inflammation and ear thickness changes in lab animals, respectively.
  • TP A 12-0-tetradecanoylphorbol- 13 -acetate
  • Figures 4A-4B include bar charts of data illustrating effects of 3HX treatments in accordance with certain embodiments on TPA-induced psoriasis based upon ear punch biopsy weight and epidermal ear thickness in lab animals, respectively.
  • Figures 5A-5B include bar charts of data illustrating % inhibitory activity and effect on serum nitric oxide level, respectively, of oral and topical 3HX treatments in accordance with certain embodiments.
  • Figures 6A-6B include plots of data illustrating effects on TPA-induced psoriasis based upon ear thickness changes in lab animals of treatments with 3HX and MTX and 3HX and BD, respectively, in accordance with certain embodiments.
  • Figure 6C includes plots of data illustrating effects of 3HX, MTX and BD treatments in accordance with certain embodiments on TPA-induced psoriasis based upon absolute ear thickness in lab animals.
  • Figure 7A includes bar charts of data illustrating % inhibition of ear inflammation in lab animals of MTX alone and in combination with 3HX in accordance with certain embodiments.
  • Figure 7B includes bar charts of data illustrating % inhibition of ear inflammation in lab animals of BD alone and in combination with 3HX in accordance with certain embodiments.
  • Figure 7C includes a bar chart of data illustrating effects of drug treatments in accordance with certain embodiments on ear biopsy weight of lab animals.
  • Figure 8 includes a bar chart of data illustrating effects of various treatments in accordance with certain embodiments on TPA-induced psoriasis based upon epidermal ear thickness in lab animals.
  • Figures 9A-9B include plots of data illustrating effects of MTX and BD on TPA induced psoriasis based upon absolute ear thickness and ear thickness change in lab animals, respectively.
  • Figure 10 includes a table of data illustrating % inhibitory activity of MTX and BD on TPA- induced psoriasis based upon ear thickness in lab animals.
  • Figures 11A includes a bar charts of data illustrating effects of MTX and BD on TPA induced psoriasis based upon ear punch biopsy weight of lab animals.
  • Figure 1 IB includes a bar chart of data illustrating % inhibition of drug treatment on TPA- induced psoriasis based upon ear biopsy weight of lab animals.
  • Figure 12 includes a table of treatments, doses, regimens, volumes and routes in accordance with certain embodiments.
  • Figures 13A-13C include bar charts of data illustrating effects of treatments in accordance with certain embodiments on TPA-induced psoriasis based upon changes in ear thickness of lab animals.
  • Figure 14A includes a table of data illustrating % inhibition of treatments in accordance with certain embodiments on TPA-induced psoriasis.
  • Figure 14B includes a bar chart of data illustrating % inhibitory activity of various treatments in accordance with certain embodiments on TPA-induced psoriasis.
  • Figures 15A-15C include bar charts of data illustrating effects of topical and oral treatments in accordance with certain embodiments on TPA-induced psoriasis based upon ear thickness in lab animals.
  • Figures 16A-16C include bar charts of data illustrating TNF-a levels in ear tissues of lab animals upon 3HX, MTX and BD treatments in accordance with certain embodiments.
  • Figures 17A-17C include bar charts of data illustrating effects of topical and oral 3HX, MTX and BD treatments in accordance with certain embodiments on IL-6 levels in ear homogenate of lab animals.
  • Figure 18 includes a table illustrating 3HX, MTX, BD and Da Huang alone (hereinafter “1HX”) treatments, doses, regimens, volumes and routes in accordance with certain embodiments.
  • 1HX Da Huang alone
  • Figures 19A-19B includes plots of data illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on imiquimod (hereinafter "IMQ")-induced psoriasis based upon absolute ear thickness of lab animals.
  • IMQ imiquimod
  • Figure 20 includes a table illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on % inhibitory activity of IMQ-induced psoriasis based upon ear thickness of lab animals.
  • Figures 21 A-21B includes bar charts of data illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on IMQ-induced psoriasis based upon ear punch biopsy weights of lab animals.
  • Figures 22A-22B includes bar charts of data illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on IMQ-induced psoriasis based upon ear thickness of lab animals.
  • Figures 23A-23B includes bar charts of data illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on IL-17 levels in lab animals.
  • Figures 24A-24B includes bar charts of data illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on IL-23 levels in lab animals.
  • Figures 25A-25B includes bar charts of data illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on IMQ-induced psoriasis in lab animals.
  • Figure 26 includes a table illustrating 3HX, MTX, and BD treatments, doses, regimens, volumes and routes in accordance with certain embodiments.
  • Figures 27A-27C include bar charts of data illustrating effects of 3HX, MTX, and BD treatments in accordance with certain embodiments on IMQ-induced psoriasis based upon ear thickness of lab animals.
  • Figure 28 includes a table illustrating effects of 3HX, MTX, and BD treatments in accordance with certain embodiments on % inhibitory activity of IMQ-induced psoriasis based upon ear thickness changes in lab animals.
  • Figures 29A-29C include bar charts of data illustrating effects of 3HX, MTX, and BD treatments in accordance with certain embodiments on IMQ-induced psoriasis based upon ear punch biopsy weights in lab animals.
  • Figures 30A-30C include plots of data illustrating effects of 3HX, MTX, and BD treatments in accordance with certain embodiments on IMQ-induced psoriasis in lab animals.
  • Figures 31A-31C includes bar charts of data illustrating effects of 3HX, MTX, and BD treatments in accordance with certain embodiments on IL-17 levels in lab animals.
  • Figures 32A-32B includes bar charts of data illustrating effects of 3HX, MTX, and BD treatments in accordance with certain embodiments on IL-23 levels in lab animals.
  • Figure 33 illustrates effects of combinations of Sheng Di Huang, Da Huang and Jin Yin Hua in accordance with certain embodiments, and of combinations of digoxin and emodin, on Body Weight in lab animals.
  • Figure 34 illustrates effects of combinations of Sheng Di Huang, Da Huang and Jin Yin Hua in accordance with certain embodiments, and of combinations of digoxin and emodin, on % Body Weight Change in lab animals.
  • Figure 35 illustrates effects of combinations of Sheng Di Huang, Da Huang and Jin Yin Hua in accordance with certain embodiments, and of combinations of digoxin and emodin, on Absolute Ear Thickness in lab animals.
  • Figure 36 illustrates effects of combinations of Sheng Di Huang, Da Huang and Jin Yin Hua in accordance with certain embodiments, and of combinations of digoxin and emodin, on Absolute Ear Thickness in lab animals.
  • Figure 37 illustrates effects of combinations of Sheng Di Huang, Da Huang and Jin Yin Hua in accordance with certain embodiments, and of combinations of digoxin and emodin, on Ear Thickness Change in lab animals.
  • Figure 38 illustrates effects of combinations of Sheng Di Huang, Da Huang and Jin Yin Hua in accordance with certain embodiments, and of combinations of digoxin and emodin, on Ear Thickness Change in lab animals.
  • Figure 39 illustrates effects of combinations of Sheng Di Huang, Da Huang and Jin Yin Hua in accordance with certain embodiments, and of combinations of digoxin and emodin, on Ear Punch Biopsy Weight in lab animals.
  • Figures 40A-40G show photographs of TP A induced inflammation in mice ears that were represented for all the experimental groups which demonstrated the gross effect of test items.
  • Figure 41 illustrates % Inhibition of Ear Inflammation in lab animals on topical treatment in accordance with certain embodiments.
  • Figure 42 illustrates % Inhibition of Ear Inflammation in lab animals on oral treatment in accordance with certain embodiments.
  • FIGS 43A-43H illustrate histopathological findings in accordance with certain embodiments.
  • Figure 44 illustrates effects of topical application of Sheng Di Huang, Da Huang and Jin Yin Hua in accordance with certain embodiments and of combinations of digoxin and emodin on epidermal ear thickness in lab animals.
  • Figure 45 illustrates effects of oral applications of Sheng Di Huang, Da Huang and Jin Yin Hua in accordance with certain embodiments and of combinations of digoxin and emodin on epidermal ear thickness in lab animals.
  • Figure 46 illustrates effects of topical application of Sheng Di Huang, Da Huang and Jin Yin Hua in accordance with certain embodiments and of combinations of digoxin and emodin on MPO activity in TP A induced mice ears.
  • Figure 47 illustrates effects of oral administration of Sheng Di Huang, Da Huang and Jin Yin Hua in accordance with certain embodiments and of combinations of digoxin and emodin on MPO activity in TP A induced mice ears.
  • Figure 48 illustrates the % Inhibition of serum Nitric oxide content on of Sheng Di Huang, Da Huang and Jin Yin Hua in accordance with certain embodiments and of combinations of digoxin and emodin treatment, in lab animals.
  • Figure 49 illustrates the effect of proliferation of Digoxin, Emodin and their combination on MDA 435 cell lines of Melanoma and Breast Cancer.
  • Figure 50 is a bar chart that illustrates the effects of certain herbs and combinations of herbs in accordance with certain embodiments on live cancer cells, including (CI) Sheng Di Huang - Rhemannia; as well as (C2) the combination of Jin Yin Hua - Lonicerae, Da Huang - Rhei, Mu Dan Pi - Moutan, and Di Gu Pi - Cortex Lycii, and (C3) the combination of Xian He Cao - Agrimoniae and Chun Gen PI - Ailanthi.
  • Figures 51-53 show plots of growth of cancer cells versus dilution factor for each of 18 different herbs in accordance with certain embodiments.
  • Figure 54 is a bar chart that illustrates the effects of certain herbs and combinations of herbs on live cancer cells.
  • compositions for treating psoriasis, eczema, or other inflammatory ailment, melanoma or other skin ailment, leukemia or other cancer or autoimmune disease, or another ailment described herein.
  • the treatment includes administering to a patient diagnosed with one or more of these ailments a treatment regimen that includes a methotrexate dose or regimen before, during or after, or combination thereof, along with periodic doses of certain
  • An example two herb combination in accordance with certain embodiments includes Da Huang and Sheng Di Huang. Another two herb combination includes Da Huang and Jin Yin Hua. Another two herb combination includes Sheng Di Huang and Jin Yin Hua. A three herb combination includes Da Huang, Sheng Di Huang and Jin Yin Hua. Each of these three herbs may be used as single herb treatments that may have efficacy at or above certain minimum doses and non- toxicity at or below certain maximum doses.
  • Da Huang is provided as an example of a one herb treatment that may be combined in a treatment regimen with methotrexate, betamethasone or another known treatment described herein.
  • these two and three herb combinations form enhanced combinative treatments for psoriasis, inflammation and skin ailments such as melanoma and eczema, or cancer or autoimmune disease or another ailment described herein.
  • combinations of two to seven herbs selected from among the following seven herbs may be administered to a patient as an effective treatment or supplement to a methotrexate treatment in accordance with certain embodiments, the seven herbs including: Da Huang, Sheng Di Huang, and Jin Yin Hua, as well as Mu Dan Pi, Di Gu Pi, Xian He Cao, and Chun Gen Pi.
  • Herbal combinations of one or more of these herbs may also include other herbs that are described below herein and/or that may be known to those skilled in the art.
  • Other combinations with and supplements to methotrexate treatments for certain ailments described herein may include an herbal combination of one or more of the described herbs with molecules, molecular extracts, or molecular combinations including one or more of emodin or digoxin, or both, and/or one or more of aucubin, vanillic acid, carvacrol, beta-sitosterol, rhein or rhapontin or another molecules described herein.
  • Herbal and molecular combinations may include other molecules, molecular extracts or molecular combinations that are described below herein and/or that may be known to those skilled in the art.
  • Other combinations may include an herbal combination of one or more herbs described herein with methotrexate, betamethasone or another known treatment described herein or understood by those skilled in the art.
  • the medicinal composition of methotrexate with an herbal combination of Da Huang and Sheng Di Huang or with an herbal combination of Da Huang, Sheng Di Huang and Jin Yin Hua may be used as an effective, non-toxic treatment for psoriasis, inflammation, melanoma or other cancer, eczema, or an auto-immune, inflammatory and/or skin-related ailment, or cancer.
  • the combination of methotrexate with an herbal combination of one or more of Da Huang, Sheng Di Huang and Jin Yin Hua can be used to provide a treatment that exhibits an increased effectiveness and/or reduced toxicity compared with treatments involving methotrexate alone or without the herbal combination of one or more of Da Huang, Sheng Di Huang and Jin Yin Hua.
  • an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua can be used as an effective, non-toxic bridge for weening a patient away from a methotrexate treatment regimen.
  • each of the one or more herbs of an herbal combination in accordance with embodiments set forth herein are several molecular constituents.
  • An observed reduction of symptoms and suffering from psoriasis, eczema, melanoma, inflammation or cancer owing to a treatment regimen including methotrexate and periodic doses of an herbal combination and/or combinations of emodin or digoxin, or both, and/or one or more of several molecular constituents with one or more of the seven herbs and methotrexate can be as a result of various combinations of active molecules.
  • a method of treating Acute Lymphoblastic Leukemia (ALL) including
  • a treatment regimen that includes periodic doses of an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or with or following a regimen including, with Vincristine Sulfate, Cyclophosphamide, Doxorubicin Hydrochloride, Methotrexate, Clofarabine, Cytarabine, Dasatinib, Daunorubicin Hydrochloride, Gleevec (Imatinib Mesylate), Nelarabine, or Oncaspar (Pegaspargase), or combinations thereof.
  • a method of treating Acute Monocytic Leukemia including administering to a patient diagnosed with AML a treatment regimen that includes periodic doses of an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or with or following a regimen including, with Cyclophosphamide, Cytarabine, Doxorubicine, Daunorubicin, Methotrexate, or Vincristine, or combinations thereof.
  • a treatment regimen that includes periodic doses of an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or with or following a regimen including, with Cyclophosphamide, Cytarabine, Doxorubicine, Daunorubicin, Methotrexate, or Vincristine, or combinations thereof.
  • a method of treating Melanoma including administering to a patient diagnosed with Melanoma a treatment regimen that includes periodic doses of an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or with or following a regimen including Paclitaxel, Cisplatin, Carboplatin, Vinblastine, Methotrexate, Vincristine or Vindesine, or combinations thereof.
  • the treatment regimen may also include Aldesleukin (Proleukin), dacarbazine, Ipilimumab (Yervoy) or Peginterferon-alpha, or combinations thereof.
  • a method of treating Melanoma including administering to a patient diagnosed with Melanoma a treatment regimen that includes periodic doses of an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or with or following a regimen including Fluorouracil or another pyrimidine analog, Pembrolizumab, methotrexate, Nivolumab, Pidilizumab, one or more monoclonal antibodies, one or more drugs that target PD-1 receptors or PD-1 inhibitors, and/or with radiation treatments such as proton therapies for treating choroidal melanomas, endolymphatic radio-isotope infusion or other radiation therapy such as external beam radiotherapy or brachytherapy, topical chemotherapy, e.g., with imiquimod or 5 -fluorouracil, and cryotherapy, photodynamic therapy, electrodesiccation, curettage, Mohs' micrographic surgery.
  • an herbal combination including
  • a method of treating psoriasis including administering to a patient diagnosed with psoriasis a treatment regimen that includes periodic doses of Sheng Di Huang and Da Huang and/or a combination of Sheng Di Huang, Da Huang and Jin Yin Hua along with Consentyx (secukinumab) or other IL-17 inhibitor, IL-12, IL-23 or TNF-a inhibitors, Otezla (apremilast) or other
  • phosphodiesterase-4 inhibitor Humira, Stelara, alefacept, methotrexate, cyclosporine,
  • hydroxycarbamide fumarates such as dimethyl fumarate, topical retinoids, monoclonal antibodies such as infliximab, adalimumab, golimumab, or certolizumab pegol, a proteasome inhibitor, Donavan's solution, vitamin A, D, D3 or related analogs or synthetic forms, paricalcitol, calcipotriol,
  • fluocinonide dithranol, decubol, psoralen, acitretin, coconut oil, mineral oil, balnoetherapy or baths in the dead sea or in formulations of dead sea or dead sea-like minerals, salts, emollients, or oils, fish oil or gluten- free dieting, UV light therapy, dermabrasion, laser therapy, cryotherapy, or combinations of two or more of these or combinations of these with other treatments or medications or compositions described herein.
  • a method of treating multiple myeloma including administering to a patient diagnosed with multiple myeloma a treatment regimen that includes periodic doses of of an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, either alone or with or following administration of a Methotrexate regimen, and/or with or following a regimen including Talidomid, Methotrexate, Revlomid or Valkade, or combinations thereof.
  • a method of treating chronic myeloid leukemia including administering to a patient diagnosed with CML a treatment regimen that includes periodic doses of of an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or with a regimen including Gleevac, Dasatinib, Sprycel, Nilotinib, Methotrexate, Tasigna, Hydroxyurea or Hydrea, or combinations thereof.
  • a treatment regimen that includes periodic doses of of an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or with a regimen including Gleevac, Dasatinib, Sprycel, Nilotinib, Methotrexate, Tasigna, Hydroxyurea or Hydrea, or combinations thereof.
  • a method of treating non-Hodgkins lymphoma including administering to a patient diagnosed with non-Hodgkins lymphoma a treatment regimen that includes periodic doses of an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or an RCHOP combination, including Retuximab or Mabtera, or both and a combination of Cyclophosphamide, and Doxorubicin
  • a method of treating Hodgkins lymphoma including administering to a patient diagnosed with Hodgkins lymphoma a treatment regimen that includes periodic doses of of an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or an ABVD combination, including Doxorubicin Hydrochloride, Hydroxydaunomycin, or Adriamycin, or a combination thereof, and Bleomycin, and Vinblastine, and dacarbazine or Procarbazine or both.
  • a treatment regimen that includes periodic doses of of an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or an ABVD combination, including Doxorubicin Hydrochloride, Hydroxydaunomycin, or Adriamycin, or a combination thereof, and Bleomycin, and Vinblastine, and dacarbazine
  • a method of treating colon cancer including administering to a patient diagnosed with colon cancer a treatment regimen that includes periodic doses of of an herbal combination including one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or Folfiri q Folfox combination, including a combination of fluorouracil -5Fu, Oxaliplatinim, irinotecan, and leucovorin or subset thereof.
  • a method of treating non-small cell lung cancer including administering to a patient diagnosed with colon cancer a treatment regimen that includes periodic doses of a combination of one or more of Sheng Di Huang, Da Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or with a regimen including Cisplatinum, etoposide, mitomycin C, or vindesine, or a combination thereof.
  • a method of treating prostate cancer including administering to a patient diagnosed with prostate cancer a treatment regimen that includes periodic doses of a combination of one or more of Sheng Di Huang, Da Huang and Jin Yin Hua, alone or with or following administration of a
  • Methotrexate regimen and/or with a regimen including Taxotere, Paclitaxel, Docetaxel, Mitoycin C, Doxorubicin, Mitozantrone, vinblastine, Etoposide, or Estramustine Phosphate, or combinations thereof.
  • a method of treating breast cancer including administering to a patient diagnosed with prostate cancer a treatment regimen that includes periodic doses of a combination of one or more of Sheng Di Huang, Da Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or with a regimen including cyclophosphamide, doxorubicin, Adriamicin, fluorouracil, 5fu, or Taxol, or combinations thereof.
  • a method of treating epidermal oral carcinoma including administering to a patient diagnosed with prostate cancer a treatment regimen that includes periodic doses of a combination of one or more of Sheng Di Huang, Da Huang and Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or with a regimen including Taxol, Carboplatinum, or Erbitux, or combinations thereof.
  • a method of treating glioblastoma including administering to a patient diagnosed with glioblastoma a treatment regimen that includes periodic doses of a combination of one or more of Sheng Di Huang, Da Huang and Jin Yin Hua, alone or with or following administration of a
  • Methotrexate regimen and/or with a regimen including TEMODAL, temozolomide, or Avastin, or combinations thereof.
  • a method of treating acute myeloid leukemia including administering to a patient diagnosed with acute myeloid leukemia a treatment regimen that includes periodic doses of a combination of one or more of Sheng Di Huang, Da Huang and Jin Yin Hua, alone or with or following administration of a methotrexate regimen.
  • Eight FAB subtypes of acute myeloid leukemia are provided below, which may be treated with said treatment regimen.
  • Methods of relieving side effects of chemotherapy, enhancing antitumor activity, improving quality of life of a patient undergoing chemo, inhibiting growth of tumors, increasing a therapeutic index of cancer therapeutic compounds for treating cancer, treating a disease, and modulating hematological or immunological activity for the treatment of a disease are also provided, including administering a combination of one or more of emodin or digoxin or Sheng Di Huang or Da Huang or Jin Yin Hua, alone or with or following administration of a Methotrexate regimen, and/or with or following a regimen including one or more of the following: Vincristine Sulfate, Cyclophosphamide, Doxorubicin Hydrochloride, Methotrexate, Clofarabine, Cytarabine, Dasatinib, Daunorubicin
  • Advantageous effects of a treatment regimen may be bolstered by further combinations with active ingredients and/or by one or more buffer molecules or one or more molecules serving as some helpful vehicle for the active molecules.
  • active ingredients and/or by one or more buffer molecules or one or more molecules serving as some helpful vehicle for the active molecules.
  • buffer molecules or one or more molecules serving as some helpful vehicle for the active molecules.
  • certain parts of one or more of the seven herbs are used such as the roots, stems, leaves, husks, branches, barks, sap, or kernels or combinations thereof.
  • the root may be used for Da Huang.
  • at least dried root tuber may be used for Jin Yin Hua.
  • at least dried flower may be used for Mu Dan Pi.
  • at least dried root bark may be used for Di Gu Pi.
  • at least dried root bark may be used for Xian He Cao, at least dried aerial part of Agrimonia Pilosa Ledeb may be used.
  • Chun Gen Pi at least dried bark of the root or stem may be used.
  • methotrexate may be administered along with or before or after administration to a patient with psoriasis, eczema, melanoma, inflammation or cancer, an herbal combination of the two herbs Sheng Di Huang and Da Huang, or two or more of the three herbs including Jin Yin Hua, or combinations of the seven herbs including Mu Dan Pi, Di Gu Pi, Xian He Cao and/or Chun Gen Pi.
  • methotrexate may be administered before, during and/or after administering any one or more of the three herbs Sheng Di Huang, Da Huang, and Jin Yin Hua, along with one or more, or even all in certain embodiments, of one or more of Mu Dan Pi, Di Gu Pi, Xian He Cao and/or Chun Gen Pi and/or one or more of an additional eleven herbs including Zi Cao, or radix arnebiae (arnebia root) or radix lithospermi (gromwell root), Xuan Shen, or radix scrophulariae (figwort root), Shi Gao or gypsum fibrosum (gypsum), Bai Shao, or radix paeoniae alba (white peony root), Chi Shao or radix paeoniae rubra (red peony root), Hong Hua or flos carthami (safflower), Da Qing Ye or folium isatidis (woad leaf), Qing Dai
  • methotrexate may be administered before, during and/or after administering any one or more of the three herbs Sheng Di Huang, Da Huang, and Jin Yin Hua, and/or one or more of the other herbs described herein, along with one or more molecules, molecular extracts or molecular compounds or constituents described herein.
  • Da Huang contains free antraquinones, anthraquinone glycosides, and bianthrones.
  • free antraquinones contained within Da Huang are alizarin, aloe emodin, chrysophanol, citreorosein, emodin, laccaic acid D, physcion, and rhein.
  • anthraquinone glycosides contained within Da Huang are l,8-dihydroxy-3-methylanthraquinone-l-0-P-D-glucoside (Palmatin), aloe emodin - ⁇ - ⁇ -D-glucopyranoside, aloe emodin ⁇ - ⁇ - ⁇ -D-glucopyranoside, chrysophanol ⁇ - ⁇ - ⁇ -D- glucopyranoside (chrysophanein), chrysophanol 8-0-P-D-glucopyranoside, emodin 1-0 ⁇ -D- glucopyranoside, emodin 3-0-P-D-glucopyranoside (Glucoemodin), emodin ⁇ - ⁇ - ⁇ -D- glucopyranoside, physcion ⁇ - ⁇ - ⁇ -D-glucopyranoside, physcion 8-0 ⁇ -D-gentiobioside, physcionin, and r
  • Da Huang Among the bianthrones contained in Da Huang are aloe emodin bianthrone, chrysophanol bianthrone, palmidins A - C, rheidins A - C, sennidins A, B and C and sennosides A - F.
  • Da Huang also includes other compounds including 2-(-2-hydroxy-propyl)-5-methyl-7- hydroxy-chromone, 2-(-2-hydroxypropyl)-methyl-7-hydroxy-chromanone, 2,5-dimethyl-7- hydroxychromone, 2-methyl-5-carboxymethyl-7-hydroxychromone, 3 napthalenes, 3,5,4'- trihydroxystilbene 4'- ⁇ -D-(2"-0-galloyl)-glucopyranoside, 3,5,4'-trihydroxystilbene 4'-0- ⁇ -0-(6"-0- galloyl)-glucopyranoside, 4'-0-methylpiceid, Rhapontin, Rheinosides A - D, Stilbene gakkates 3,5,4'- rtihydroxystilbene 4'-0- ⁇ -D-glucopyranoside, Stilbene piceid and Tannins.
  • Da Huang is well known as a purgative agent.
  • the active constituents are the combined anthraquinones, especially sennosides.
  • the content of sennosides correlates with the purgative activity of rhubarb.
  • Table 1 illustrates the oral purgative ED50 values of the anthraquinones
  • sennosides are hydrolysed by microbial ⁇ -glycosidase in a stepwise fashion to the corresponding sennidins via 8-monoglycosides.
  • the resulting metabolites sennidins were further reduced, possibly by a reductase bound to cell membranes of intestinal bacteria, to rheinanthrone as the purgative principle.
  • HBV hepatitis B virus
  • HBsAg hepatitis B virus surface antigen
  • Rhubarb exhibited inhibition against staphylococci, Streptococcus hemolyticus
  • the main antibacterial components were the anthraquinone derivatives with the structure of 1 ,9- dihydroxyanthraquinone. 3-Carboxyrhein, hydroxyaloe-emodin and hydroxy emodin showed the most potent antibacterial activity.
  • the bacteriostatic concentrations of rhein, emodin and aloe-emodin against staphylococci, streptomycin, Corynebacterium diphtheria, Bacillus subtilis, B. anthracis and Salmonella tophy were mitochondrial respiratory chain of microorganisms. Respiration of
  • Staphylococcus aureus was strongly inhibited by emodin, aloe-emodin and rhein. Rhein, emodin and rhein specifically interfered with the redox function NADH dehydrogenase.
  • aqueous, ethanolic and ether extracs of rhubarb are also antifungal against many pathogenic fungi, including Achorion schoenleini, Trichopphyton concentricum, T. violaceum, T. gypsum, Nocardia asteroids, Epidermophyton flocosum and Sporotrichum schenckii.
  • Achorion schoenleini Trichopphyton concentricum
  • T. violaceum T. gypsum
  • Nocardia asteroids Epidermophyton flocosum
  • Sporotrichum schenckii Sporotrichum schencki.
  • the decoction of rhubarb exhibited inhibition against the influenza virus.
  • the minimal effective dose in chicken embryo in vitro and semi in vivo was 5 mg per embryo.
  • Cysophanein and physcionin also exhibited moderate cytotoxic activity against several types of carcinoma cells.
  • Emodin also markedly decreased the mutagenicity of 1-nitropyrene (1- NP) in a dose dependant manner in Ames-microsomal test with S. typhimurium TA98 and the genotoxicity in SOS chromotest with E. coli PQ37. Furthermore, emodin significantly inhibited the formation of 1-NP DNA adducts in S. typhimurium TA98. The results suggest that emodin acts as a blocking and/or suppressing agent to reduce the direct-acting mutagenicity of 1-NP.
  • Rhubarb is also in TCM as a hemastatic agent. The hemastatic activity has been proved experimentally and clinically. Rhubarb is effective for both external and internal hemorrhage. It was effective in the treatment and prevention of experimental gastric bleeding and ulcer formation in rats. Significant therapeutic effects of the powdered rhizome of R. palmatum in the treatment of
  • gastrointestinal bleeding were also reported. It reduces coagulation time and the permeability and fragility of capillaries. It increases fibrinogen and promotes bone marrow to produce platelets.
  • Emodin at 3 X 10 ⁇ 7 -3 X 10 ⁇ 4 M dose-dependently suppressed the responses of human mononuclear cells to phytohemagglutinin and mixed lymphocyte reaction. It was further found that after exposure to emodin (10 ⁇ 6 M) the production of interleukin-1 (IL-1) and interleukin-2 (IL-2) and the expression of IL-2 receptor were all decreased, Emodin may be a new template for the development of better immunosuppressive agents for use against transplantation and autoimmune disease.
  • IL-1 interleukin-1
  • IL-2 interleukin-2
  • Rhubarb can stimulate construction of the gallbladder and relax Oddi's sphinctercan, thus promoting bile secretion. It also increases the contents of bilirubin and bile acid.
  • Oral administration if emodin and rhein provoked marked diuretic, natriuretic and kaliuretic effects in rabbits.
  • Oral administration of rhubarb increased urinary excretion of sodium and potassium, alkalizing urine to a pH value as high as 8.4.
  • Rhubarb also inhibits the activites of pepsase, trypsase, pancreatic amylase and pancreatic lipase. It lowers blood pressure and blood cholesterol levels.
  • Intraperitoneal administration of 15 mg/kg of emodin exhibited antiinflammatory activity against carrageenin-induced pedal inflammation in rats. In the same dosage it also showed
  • Mu Dan Pi contains Apiopaeonoside, Benzoyloxypaeoniflorin, Benzoylpaeoniflorin,
  • the decoction of the root bark exhibited a strong antibacterial activity in vitro against the following bacteria: Bacillus subtilis, Escherichia coli, Salmonella typhi, S. paratyphi, Protues vulgaris, Pseudomonas aeruginosa. Staphylococcus aureus, Strephtococcus hemolyticus, Diplococcus pneumoniae and Vibrio cholerae. Paeonol was one of the antibacterial components; its MIC values were 1 :2000 against Staphlococcus aureus, 1 : 1500 against Bacillus subtilis and Escherichia coli. Anti-inflammatory Effect of Mu Dan Pi
  • the 70% methanolic extract of the root bark inhibited rat paw swelling induced by carrageenin.
  • Paeonol was found active in inhibiting rat paw swelling induced by dextran, acetic acid or carrageenin. It also inhibited the increase of intra-abdominal capillary permeability of mice and cutaneous capillary permeability of guinea pigs caused by acetic acid or 5-HT.
  • the water soluble fraction free from paeonol as well as the glycoside fraction also exhibited a significant inhibitory action on rat paw edema due to carrageenin.
  • the water-soluble fraction was also effective in either preventing or treating adjuvant-induced arthritis in rats.
  • the methanolic extract, the glycosidic fraction and paeonol inhibited blood platelet aggregation.
  • ADP- or collagen-induced human plateet aggregation was inhibited by paeonol.
  • the formation of thromboxan B 2 was also inhibited but the formation of 12- hydroxy-5,8,10,14-eocpsatetraenoic acid from C-arachidonate was stimulated.
  • paeonol inhibited the formation of prostanoids such as prostaglandins and thromboxanes from C-arachidonate in rat peritoneal macrophages.
  • the anti-inflammatory action of the root bark was related to the inhibitory effects of paeonol on prostanoid synthesis. Hypotensive Effect of Mu Dan Pi
  • the blood pressure of dogs with essential or renal hypertension was significantly reduced after oral administration of 5 g/kg of the decoction of the root bark for 5 days and 10 g/kg for two more days.
  • the blood pressure of dogs with renal hypertension was also lowered after oral of lOg/kg of the decoction free paeonol for 10 days.
  • Oral administration of 0.5-1.0 g/kg of paeonol also produced hypotensive action renal hypertensive dogs and rats.
  • paeonol Intraperitoneal or oral administration of paeonol decreased the spontaneous activity of mice, antagonized caffeine-induced hyperactivity and prolonged cyclobarital-induced sleep. At higher doses, paeonol caused disappearance of the righting reflex in mice. It also antagonized convulsions due to cardiazol, strychnine, nicotine and electric shock. Furthermore, paeonol was found to have antipyretic and analgesic activities. Paeonol decreased the body temperature of normal mice and the mice with typhoid and paratyphoid vaccine-induced fever. Oral administration of paeonol produced an analgesic effect against acetic acid-caused writhing and tail pain by pressing in mice. Effect on Obesity of Mu Dan Pi
  • the aqueous extract of the herb was given as drinking water at the concentration of 0.5% to (SLN x C 3 H/He) Fi obese mice between 3 and 32 weeks of age.
  • the treatment resulted in a significant decline, particularly in males, in food intake and in the Lee index, An index of obesity, and
  • Paeonol exhibited anticholinergic and antihistaminic actions on isolated ileum of mice and guinea pigs. It also prevented stress ulcer in mice and inhibited gastric secretion in rats and
  • the extract of the root bark and paeonol were also of antimutagenic activity. They decreased the frequency of mutations induced by 4-nitroquinoline 1 -oxide in Escherichia coli WP2s.
  • Sheng Di Huang contains 4-(a-L-rhamnopyranosyloxy)-3-methoxybenzoylajugol, Aceutoside, Ajugol, Aucubin, Campesterol, Castanosides A and F, Catalpol, digoxin Echinacoside, E- feruloylajugol, Isoacetoside, Jioglutoside A and B, Jionosides A&B, Leonuride, Mannitol, Melittoside, p-courmaroylagujol, p-hydorxybenzoylajugol, Purpureaside C, Rehmaglutins A, Rehmaionosides A-C, Rehmanniosides A-D, Rehmapicroside, Vanilloylajugol, Z-feruloylajugol, and ⁇ -sitosterol, PHARMACOLOGY
  • the herb was able to stop the decrease of plasma corticosterone concentration due to administration of dexamethasone and prevent the adrenal cortex from atrophy.
  • the corticosterone level in rabbits receiving dexamethasone was increased at week 4 and week 6 when the herb was
  • This mixture also antagonized the inhibitory action of dexamethason on the early morning Cortisol secretion peak in 12 normal subjects as tested in diurnal dexamethason suppression test.
  • the crude extract (8 mg) of the root when incubated with the liver sections of rabbits, protected Cortisol from being reduced on the double bond between C 4 and C 5 , and the ketone at C 3 and being degraded of the hydroxyl groups at C 17 and C 21 , and the ketone at C 2 o, thus delaying the metabolism of Cortisol in the liver.
  • plasma Cortisol could still be kept at a nearly normal level.
  • the mechanism is believed to be a kind of competitive effect which influenced the binding of cortical hormone to the receptors and affected the uptake of corticosteroid hormone by the liver cells, thereby slowing down the catabolism of Cortisol.
  • Intravenous injection of 2.5 ml of the root extract produced a diuretic effect in anesthetized dogs. This action may be related to the cordial and renal vasodilation activities.
  • the coagulation time in rabbits was reduced after giving the yellow needle crystal obtained from the ethanolic extract of the root.
  • Intraperitoneal administration of 10 g/kg of the decoction or ethanolic extract, or oral administration of the charred herb shortened the bleeding time in mice with tail wounds.
  • Jin Yin Hua contains 2,6,6-trimethyl-2-vinyl-5-hydroxytetrahydropyran, Benzyl-alcohol, Carvacrol, Cis and trans-2-methyl-2-vinyl-5-(a-hydroxyisopropyl)-tetrahydrofuran, Epivogeloside, Eugenol, Geraniol, Hex-l-ene, Hex-3-en-l-ol,
  • Isochlorogenic acid a (3,5-dicaffeoyl quinic acid), Linalool, Loganin, Lonicerin, Lonicerin, Luteolin, Methylcaffeate, Pinene, Saponins with oleanolic acid, Secologanin dimethylacetal,
  • Staphylococcus aureus Streptococcus hemolyticus, Escherichia coly, Shigella dysenteriae, Vibrio cholera, Salmonella typhi, S. oaratyphi, Diplococcus pneumoniae, Neisseria meningitides, Pseudomonas aeruginosa and Mycobacterium tuberculosis. It also potentiated the action of penicillin against the drug-resistant Staphylococcus aureus. Chlorogenic acid and isochlorogenic acid are believed to be the chief antibacterial components of the flower. Luteolin also showed an antibacterial activity.
  • mice receiving the LD dose of Pseudomonas aeruginosa or its endotoxin survived after given 7.5 g/kg of the injection solution of the flower by intraperitoneal administration.
  • Intravenous administration of 6 g/kg of the distillate of the flower was also therapeutically effective in rabbits poisoned by the endotoxin of Pseudomonas aeruginosa.
  • Antifunal activity was observed with the aqueous extract of the flower against Microsporum ferrugineum and Nocardia asteroids.
  • the decoction of the flower inhibited influenza virus, ECHO virus and herpes virus.
  • Intraperitoneal administration of 0.25 g/kg of the flower inhibited carrageenin-induced paw edema in rats. Given twice a day at 8 g/kg for 6 days by Intraperitoneal injection, the extract of the flower showed antiexudative and antihyperplastic effects on croton oil-induced granuloma.
  • Intraperitoneal administration of the injection solution increased the phagocytic activity of the inflammatory cells in mice.
  • the decoction diluted to 1 : 1280 concentration was still able to promote leukocytic phagocytosis.
  • Intraperitoneal administration of an aqueous-ethanolic extract of the flower of L. japonica to mice on day 8 after mating decreased pregnancy in the test animals dose-dependently.
  • Intrauterine and intra-amniotic administration of the extract killed the fetuses in dogs and caused abortion in monkeys, respectively.
  • the extract of the flower exhibited a mild prophylactic effect against experimental gastric ulcer in rats when given orally.
  • Large oral doses of chlorogenic acid increased gastrointestinal peristalsis and promoted gastric and bile secretion. Chlorogenic acid had a stimulant effect on the isolated rat uterus.
  • Di Gu Pi contains 5a-stigmastan-3 6-dione, Betaine, Cinnamic acid, Kukoamine A, Linoleic acid, Lyciumamide, Melissic acid, Sugiol, and ⁇ -sitosterol
  • the aqueous or alcoholic extract of the herb given orally or by injection, produced a significant antipyretic effect in rabbits with fever induced by pyrogen. Betaine was also active. A strong antipyretic effect was also exhibited by the aqueous fraction of the alcoholic extract at doses ranging from 0.75 to 7.5g/kg equivalent of the crude drug. The precipitates of the extract from lead salt also showed comparable antipyretic activity to synthetic antipyretic analgesics.
  • Oral administration of the decoction of the herb decreased blood glucose level in rabbits by 14% in average; this action lasted for 7-8 h. The peak action was observed 3 to 4 h after
  • the decoction, macerate, tincture and injection solution of the herb produced a significant hypotensive effect in anesthetized dogs, cats, rabbits by intravenous or intramuscular administration and in anaesthetized rats by oral administration. Repeated intravenous administration at lower doses did not induce rapid tolerance. Intravenous injection of 0.375 g/kg of the injection solution resulted in sudden drop of blood pressure and death of anesthetized dogs. Bradycardia, prolongation of PR interval and depressed T wave in the ECG were observed. Kukoamine A induced hypotension in rats when given intravenously at a dose of 5 mg/kg.
  • Staphylococcus aureus It was a weak bacteriostatic against Mycobacterium tuberculosis. In the primary monolayer tissue culture of the embryonic renal cells, the decoction prevented the pathogenic changes in the cells due to Asian influenza virus A JK strain.
  • the 100% injection solution of the bark showed stimulation effects on normal rat uterus and isolated mouse uterus.
  • the activity of 1 ml of the solution was comparable to that of 0.054 unit of pituitrin.
  • herba agrimoniae hairyvein agrimonia herb
  • Xian He Cao contains Agrimols A, B, C, D and E, Agrimoniin,
  • Agrimonolide Agrimorphol, Apigenin-7-glucoside, Caffeic acid, Ellagic acid, Gallic acid, Luteolin-7-glucoside, Pendinculagin, Potentillin, and Quercetin
  • the winter sprout of the herb is used in folk medicine to expel tenia and the active principle was found to be agrimophol.
  • Agrimophol acts directly on the parasite. It inhibits the glycogenolysis, aerobic and anaerobic metabolism in the parasite.
  • the herb and agrimophol are also lethal to some other parasites, such as Trichomonas vaginalis, blood fluke and roundworm.
  • Antibacterial Activities of Xian He Cao are also lethal to some other parasites, such as Trichomonas vaginalis, blood fluke and roundworm.
  • luteolin-7-glucoside Six compounds, luteolin-7-glucoside, apigenin-7glucoside. Quercetin, ellagic acid, caffeic acid and gallic acid, isolated from the herb were active against bacillary dysentery. Combination use of luteolin-7-glucoside and ellagic acid, apigenin-7-glucoside and apigenin-7-glucoside was more effective than the respective individual compounds.
  • Agrimoniin had antitumour activity when given as a pre- or posttreatment.
  • a single dose of 10- 30 mg/kg prolonged the life span of mice bearing MM 2 tumors or yielded cures when given
  • Agrimoniin also inhibited the growth of MH-134 and Meth-A solid tumors in mice. It was strongly cytotoxic to MM 2 cells in vitro, but the activity was almost completely abolished by the addition of fetal calf serum to the culture.
  • Intraperitoneal administration of agrimoniin increased the number of peripheral white blood cells and the proportion of monocytes.
  • the antitumor activity of agrimoniin appeared to be due to its
  • Intravenous administration of the alcoholic extract of the herb increased blood pressure and stimulated respiration in anesthetized rabbits and dogs, but the alcohol-soluble fraction of the aqueous extract lowered blood pressure in rabbits. Perfused into the blood vessels of rabbit ear and frog hind limb, it caused vasoconstriction at low concentrations and vasodilation at high concentrations.
  • the extract and agrimoniin increased the heart rate and cardiac contractility of frogs and toads.
  • the alcohol-soluble fraction of the aqueous extract inhibited the isolated frog heart.
  • cortex ailanthi (tree-of-heaven bark)
  • Chun Gen Pi contains l-(l ',2'-dihydroxyethyl)-4-methoxy- ⁇ -caboline, l-(2'-hydroxyethyl)-4- methoxy- ⁇ -carboline, l-(2-hydroxy-l-methoxy)-ethyl-4-methoxy- ⁇ -carboline, 13(21)-dehydro- glaucarubinone, 13(21)-dehydroglaucarubolone, 1 -acetyl -4-methoxy- ⁇ -carboline, 1 -carbamoyl- ⁇ - carboline, 1-carbomethoxy- ⁇ -carboine, l-hydroxycanthin-6-one, l-methoxycanthin-6-one, 1- methoxy-canthin-6-one-3 -oxide, 5-hydroxymethylcanthin-6-one, 6-methoxy- ⁇ -carboline- 1 -carboxylic methyl ester, A
  • Glaucarubinone and ailanthone showed amebicidal activity in vitro against the parasite
  • Entamoeba histolytica Some quassinoids markedly inhibited the growth of chloroquine-resistant Plamodium falciparum. Glaucarubinone produced complete inhibition at 0.0006 ⁇ g/ml. Ailanthone also showed potent antiulcer activity.
  • Aloe emodin has a molecular weight around 270.24 g/mol. As to its anti-cancer activity, aloe emodin exhibits cytotoxicity in SCC of tongue, cervix cancer cells; and apoptoticity through MAPK- JNK cascade in hepatoma cells. Aloe emodin also tends to induce P53 and apoptosis. In addition, the cytotoxicity of aloe emodin induces effects in melanoma, and gastric carcinoma. As to its antiinflammatory activity, aloe emodin exhibits anti TNF and anti virality in enveloped viruses- HSV, PSV, VSV, and INF.
  • Aloe emodin also decreases COX2 and INOS expression in inflammation, and increases IFN in JEV and EV71. Aloe emodin may also be ingested for its properties as a laxative. Use of aloe emodin can induce nausia, and intestinal contraction causing abdominal pain. Long use of anthraquinones can lead to kidney and liver damage. The half-life of aloe emodin is about 78 min.
  • Chrysophanol has a molecular weight around 254.24 g/mol. As to its anti-cancer activity, chrysophanol exhibits necrosis in hepatic cancer cells, including ATP change and ROS cascade.
  • Chrysophanic acid inhibits EGFR in colon cancer cells.
  • chrysophanol can serve as an antiseptic, bactericide, candidicide, and/or cathartic.
  • chrysophanol can be used as an anti-staph aurus and an anti-bacilus subtilis.
  • Chrysophanol can be used to suppress the activation of NF-kB. and caspase-1 in LPS-stimulated macrophages.
  • Chrysophanol is also an anti polio virus compound. Chrysophanol an be used as a hemostat and as a pesticide, and can be used in the treatment of menorrhagia, including bleeding following abortion, epistaxis, functional uterine bleeding and thrombocytopenia. Chrysophanol acts as a purgative, and can be used to converts aloe emodin through P450 in the liver. Emodin and chrysophanol may be ingested in combination as an anti cancer treatment agent. Chrysophanol has a half life of about 2.75 hours.
  • emodin has a molecular weight around 270.24 g/mol. As to its anti-cancer activities, emodin exhibits pro apoptoticity in prostate cancer cells through P53, and P21. Emodin increases ROS, and improves chemotherapy effect in prostate cells which are drug resistant. Emodin exhibits pro apoptoticity through inhibition of IL6 in myltiple myaloma. Emodin exhibits anti- matastaticityO through integrins effect. Emodin decreases HER2 in breast cancer and improves chemotherapoitic effect. Emodin induces cytotoxis in tongue carcinoma, and inhibits NFkB and other pro inflammatory cytokines.
  • emodin may be used as an anti ulcer agent through Hpylori destruction and change in gastric fluid. Emodin induces a stabilizing effect on atherosclerotic plaque in vessels, and improves insulin and glucose changes in type 2 diabetes. Emodin promotes anti plasmodium against malaria, and may be used as an
  • Emodin has a half-life of approximately 227 min and converts to two active metabolites through P450 in the liver.
  • Rhein has a molecular weight around 284.22 g/mol.
  • rhein acts as an anti proliferative in hepatic carcinoma, breast cancer, SCC of lungs, and cervical cancer. Rhein improves taxol effect in breast cancer, and inhibits nasopharengeal carcinoma and EGFR. Rhein serves as a sinergist with mitomycin. Rhein exhibits cytotoxicity in tongue carcinoma. Rhein may be used for anti angiogenesis.
  • rhein exhibits anti fibroticity, and promotes anti proliferation of hepatic cells through inhibition of TGFbl . Rhein may be used as an anti oxidant.
  • Rhein decreases IL1B, and IL18 proinflammatory cytokines. Rhein is also anti bacterial, and may be used against staph. Aurus. Rhein also increases sensitivity to ADH (drug). Rhein has a half-life of about 205 min (approx). Rhein is hydrophobic, and may be combined with lysin in order to be hydrophilic, as rhein lysinate.
  • Chrysophanein exhibits significant in- vitro cytotoxic activity in cancer cell lines
  • RHAPONTIN Rhapontin has a molecular weight of around 420.41 g/mol. As to its anti-cancer activities, rhapontin induces apoptosis and suppresses KATO III cell-growth in stomach cancer. Rhapontin also provides protective effects on LDL and erythrocytes against oxidative damage. Rhapontin has a half life of about 23.5 minutes.
  • Stilbene piceid has a molecular weight around 390.2 g/mol. As to its anti-cancer activities, stilbene piceid inhibits DNA synthesis in LLC cells. Stilbene piceid also has an inhibitory effect on lipoxygenase. Stilbene also exhibits antioxidant activity and inhibits alpha-glucosidase. Stilbene piceid also inhibits lipid peroxidation induced by ADP and NADPH in liver microsomes. Stilbene acts directly on smooth muscle to promote pulmonary artery relaxation.
  • Tannin has a molecular weight around 500-3000 g/mol.
  • tannin suppresses the growth of MCF-7 breast cancer cells.
  • Geraniin a form of tannin separated from geranium, causes cell death through induction of apoptosis. Tannin exhibits different antiproliferative effects against cervical and colon cancer cells grown in vitro.
  • tannin modulates inflammatory cell signaling in colon cancer cells. Tannin promotes apoptosis through induction of p53 non-small cell lung cancer cells.
  • tannin in tomato suppresses COX-2 expression.
  • Tannin can be used as an in vitro antioxidant and/or antiplatelet and also as an anti-inflammatory due to its free radical scavenging effects. Tannin may be used for its antiviral, antibacterial and/or antiparasitic effects. Tannin can be used in the treatment of HFE hereditary hemochromatosis. Tannin is capable of reversing 6-hydroxy dopamine induced toxicity. Tannin has a dental use, as well, as tannin-fluoride preparation reduces gingival inflammation around abutment teeth. A large intake of tannins may cause bowel irritation, kidney irritation, liver damage, irritation of the stomach and/or gastrointestinal pain.
  • Tannins inhibit the absorption of minerals such as iron which may, if prolonged, lead to anemia. Tannins are present in soil, plants, water, tea, wine, and fruit. Tannin has a half life of about 3.15 hours.
  • Carvacrol also known as cymophenol, has a molecular weight around 150.217 g/mol. As to its anti-cancer activities, carvacrol promotes anti-tumor effects on human metastatic breast cancer cells, including MDA-MB 231. Carvacrol is a potent inhibitor of cell growth inHuman Non-Small Cell Lung cancer. Carvacrol also inhibits growth of myoblast cells even after activation of mutated N-ras oncogene. As to its anti-inflammatory activities, carvacrol activates PPAR and suppresses COX-2 inflammation. Carvacrol may be used for its antiproliferative and antiplatelet properties.
  • Carvacrol is present in the essential oil of Origanum vulgare, oil of thyme, oil obtained from pepperwort, and wild bergamot. Carvacrol inhibits the growth of several bacteria strains, e.g. Escherichia coli and Bacillus cereus, and in pseudomonas aeruginosa, carvacrol disrupts the bacteria membrane. Carvacrol may be used for its antioxidant activity. Carvacrol has a half life of about 1.29 hours.
  • Eugenol has a molecular weight of about 164.2 g/mol.
  • Eugenol induces apoptosis in human colon cancer cells, and inhibits invasion and angiogenesis of gastric carcinogenesis induced by
  • Eugenol is also used in perfumeries, flavorings, essential oils and in medicine as a local antiseptic and anesthetic. Eugenol may be used for its antioxidative properties. Eugenol exhibits hepatotoxicity. An overdose of eugenol may induce convulsions, diarrhea, nausea, unconsciousness, dizziness, and/or rapid heartbeat. Eugenol can be allergenic.
  • Eugenol may express carcinogenicity through oxidative DNA damage by its metabolite.
  • Eugenol has a half-life of 1.975 hours, and under certain conditions, may have a half life up to 4 hours or even 18 hours.
  • Geraniol has a molecular weight of about 154.25 g/mol. As to its anti-cancer activities, Geraniol promotes an antiproliferative mechanism in human pancreatic adenocarcinoma cells.
  • Geraniol also promotes anti-proliferative and cell cycle regulatory effects in human breast cancer cells. Geraniol can cause a 2-fold reduction of thymidylate synthase and thymidine kinase expression in colon cancer cells. Geraniol, as a component of plant essential oils, sensitizes human colon cancer cells to 5-fluorouracil treatment. Geraniol suppresses pancreatic tumor growth without significantly affecting blood cholesterol levels. As to its anti-inflammatory activities, Geraniol diminishes the levels of inflammatory markers induced by pamidronate stimuli in vitro and in vivo. Geraniol also promotes inhibitory effects on nitric oxide and prostaglandin E 2 production in macrophages.
  • Geraniol is a component of rose oil, palmarosa oil, and citronella oil, and small quantities of geraniol are in geranium and lemon, has a rose-like odor and is commonly used in perfumes. Geraniol can be used as effective plant-based mosquito repellent. Geraniol is found in cigarettes. As to biologic use, ion- exchange iontophoresis combined with geraniol is a highly effective transdermal delivery system.
  • Geraniol suppresses Candida cell growth in the vagina and its local inflammation when combined with vaginal washing. Gernaiol is also allergenic. Geraniol has a half life of about 0.713 hours.
  • Luteolin has a molecular weight of 286.24 g/mol.
  • luteolin particularly in combination with standard anticancer drugs such as cisplatin, serves as a HDAC inhibitor, e.g., for the treatment of lung cancer.
  • Luteolin promotes synergistic/additive growth inhibitory effects and may be effective in chemoprevention treatment of head and neck and lung cancers.
  • Luteolin induces Gl arrest in human nasopharyngeal carcinoma cells. Luteolin not only protects DNA from oxidative damage, but also increases repair activity in Caco-2 cells. A low concentration of Luteolin has little toxic effect on cancer cells, but such low concentrations can sensitize chemotherapeutic drugs in various cancer cell lines. Luteolin selectively inhibits
  • Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin.
  • Luteolin is a PDE4 inhibitor and a general phosphodiesterase inhibitor, and an Interleukin 6 inhibitor. Luteolin inhibits inflammatory response and improves insulin sensitivity in the endothelium. Luteolin prevents LPS-induced TNF-a expression in cardiac myocytes through inhibiting NF-KB signaling pathway. Luteolin inhibits myelin basic protein-induced human mast cell activation and mast cell-dependent stimulation of Jurkat T cells. Luteolin inhibits cyclooxygenase-2 expression and scavenges reactive oxygen species.
  • Luteolin is found in leaves, but it is also seen in celery, thyme, dandelion, rinds, barks, clover blossom and ragweed pollen. Luteolin is useful in the prevention and treatment of skin photoaging. Luteolin inhibits microglia and alters hippocampal-dependent spatial working memory. Luteolin enhances insulin sensitivity via activation of PPARy transcriptional activity in adipocytes. Luteolin can induce nausea, vomiting and gastric hypersecretion. Luteolin has a half life of about 1.2 hours.
  • achyranthoside H methyl ester As to the anti-cancer activities of saponins with oleanolic acid, achyranthoside H methyl ester, a novel oleanolic acid saponin derivative from Achyranthes fauriei roots, induces apoptosis in human breast cancer MCF-7 and MDA-MB-453 cells via a caspase activation pathway. Saponion with oleanolic acid exhibit insecticidal activity against the Mexican bean beetle larvae (Epilachna varivestis).
  • Vanillic acid has a molecular weight of 168.14672 g/mol. Vanillic acid suppresses metastatic potential of human cancer cells through PI3K inhibition and decreases angiogenesis in vivo. Vanillic acid enhances the activity of human lymphocyte proliferation and secretion of IFN-gamma. Vanillic acid has a beneficial effect on DSS-induced ulcerative colitis, thereby manifesting its usefulness in the regulation of chronic intestinal inflammation. Phenolic compounds in mushroom Lentinula edodes (shiitake) are hepatoprotective through their suppression of immune-mediated liver inflammation. Vanillic acid is found in the root of Angelica sinensis, and in olive oil.
  • Vanillic acid promotes reduced cellular tyrosinase activity, DOPA oxidase and melanin contents, as well as down-regulated expressions of melanocortin-1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related proteins 2 (TRP-2) and TRP-1.
  • M1R melanocortin-1 receptor
  • MITF microphthalmia-associated transcription factor
  • TRP-2 tyrosinase-related proteins 2
  • Vanillic acid contributes to the prevention of the development of diabetic neuropathy by blocking the methylglyoxal-mediated intracellular glycation system.
  • There exist an oxidized form of vanillin. Vanillic acis has a half life of about 10.552 hours.
  • a-terpineol exhibits antiproliferative effects on erythroleukemic K562 cells
  • a-terpineol inhibits gene expression of the IL-6 receptor
  • a-terpineol suppresses fMLP-, LPS- and PMA-stimulated superoxide production
  • a-terpineol is found in cajuput oil, pine oil, and petitgrain oil, and is a common ingredient in perfumes, cosmetics, and flavors and tea.
  • a-terpineol demonstrates different degrees of growth inhibition against 15 different genera of oral bacteria, a- terpineol can cause postural hypotension in pine oil, and can cause eye irritation. There are three isomers, alpha-, beta-, and gamma-terpineol. Alpha-terpineol has a half life of about 1.245 hours.
  • Aucubin has a molecular weight of 346.32978 g/mol.
  • Antiproliferative activity is through cell cycle arrest and apoptosis in human non-small cell lung cancer A549 cells.
  • adenocarcinoma adenocarcinoma, A431-skin carcinoma of epithelial origin.
  • Aucubin enhance the activity of human lymphocyte proliferation and secretion of IFN-gamma.
  • Aucubin is found in the leaves of Aucuba japonica (Cornaceae), Eucommia ulmoides
  • Aucubin protects against liver damage induced by carbon tetrachloride or alpha-amanitin, particularly when dosed intra-peritoneally.
  • Aucubin provides neuroprotection in primary diabetic encephalopathy.
  • Aucubin treatment can lower blood glucose.
  • Aucubin can produce an increase in the level of lipid peroxidation and a decrease in activities of antioxidant enzymes in liver and kidneys.
  • Aucubin has a half life of about 42.5 minutes.
  • Digoxin also known as digitalis, has a molecular weight of 780.938 g/mol. Digoxin treatment can inhibit HIF-1 alpha synthesis and block tumor growth. Digoxin induces apoptosis in a human acute T-cell lymphoblastic leukemia cell line. Digoxin can serve as a specific neuroblastoma growth inhibitor and an unspecific inhibitor of angiogenesis.
  • Digoxin is widely used in the treatment of various heart conditions, namely atrial fibrillation, atrial flutter and sometimes heart failure that generally cannot be controlled by other medication.
  • Digoxin increases myocardial contractility, such that the heart rate is decreased, while blood pressure increases as stroke volume is increased, leading to increased tissue perfusion.
  • Digoxin improves myocardial efficiency due to improved hemodynamics, and improves the ventricular function curve.
  • Digoxin affects the kidney by increased renal blood flow and increased GFR. A mild diuretic effect is seen typically only in heart failure.
  • Digoxin may cause AV junctional rhythm and ectopic beats (bigeminy) resulting in ventricular tachycardia and fibrillation.
  • Digoxin can induce loss of appetite, nausea, vomiting and diarrhea as the gastrointestinal motility increases.
  • Other common effects of Digoxin are blurred vision, visual disturbances (yellow- green halos and problems with color perception), confusion, drowsiness, dizziness, insomnia, nightmares, agitation, and depression, as well as a higher acute sense of sensual activities.
  • Less frequent adverse effects of digoxin (0.1%-1%) include: acute psychosis, delirium, amnesia, convulsions, shortened QRS complex, atrial or ventricular extrasystoles, paroxysmal atrial tachycardia with AV block, ventricular tachycardia or fibrillation, and heart block.
  • Dangerous interactions can occur between digoxin and verapamil,amiodarone, erythromycin, and epinephrine.
  • the efficacy of chemotherapeutic agent substrates of Pgp may be strongly reduced in patients taking digoxin.
  • Digoxin treatment increases the risk of invasive breast cancer among postmenopausal women.
  • Digoxin has a half-life around 36 hours.
  • Isoacetoside as an extract from Tecoma stans, exhibits a cytotoxic effect on human
  • hepatocarcinoma cells Hep-G2
  • Isoacetoside has a half life of about 3.7-6.4 hours.
  • ⁇ -sitosterol or beta-sitosterol, has a molecular weight around 414.71 g/mol.
  • ⁇ -sitosterol may be used to treat prostatic carcinoma and breast cancer, ⁇ -sitosterol may have chemopreventive potential by virtue of its radical quenching ability in vitro, with minimal toxicity to normal cells, ⁇ - sitosterol also attenuates beta-catenin and PCNA expression, making it a potential anticancer drug for colon carcinogenesis, ⁇ -sitosterol significantly inhibits the growth, and induces the apoptosis, of SGC- 7901 human stomach cancer cells in vitro.
  • beta-sitosterol has a strong potential as a therapeutic agent for preventing cancers such as fibrosarcoma.
  • Beta-sitosterol is an effective apoptosis-promoting agent and that incorporation of more phytosterols in the diet may serve a preventive measure for breast cancer.
  • An anti-microtubule characteristic of beta-sitosterol may contribute to the proliferation inhibition of SiHa cells in cervical cancer, ⁇ -sitosterol activates the sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells, ⁇ -sitosterol promotes anti-asthmatic actions that may be mediated by inhibiting the cellular responses and subsequent release/synthesis of Th2 cytokines, ⁇ -sitosterol may have therapeutic potential in allergic asthma.
  • ⁇ -sitosterol is found in Nigella sativa, pecans, Serenoa repens (saw palmetto), avocados, Curcurbita pepo (pumpkin seed), Pygeum africanum, cashew fruit, rice bran, wheat germ, corn oils, soybeans, sea-buckthorn, wolfberries, and Wrightia tinctoria.
  • ⁇ -sitosterol reduces blood levels of cholesterol, and is sometimes used in treating
  • Beta-sitosterol is a naturally occurring phytosterol that may be used to cure atherosclerosis, diabetes, cancer, and inflammation and is also an antioxidant, ⁇ -sitosterol has a half life of about 0.966 hours.
  • Beta-Sitosterol should be avoided during pregnancy and breast-feeding, since it is not proven to be benign with regard to potential effects on unborn and newborn children.
  • ⁇ -Sitosterol is also not recommended for individuals with sitosterolemia, a rare inherited fat storage disease, because people with this condition have too much ⁇ -sitosterol and related fats in their system, taking ⁇ - sitosterol will only worsen this condition.
  • High levels of ⁇ -sitosterol concentrations in blood have been correlated with increased severity of heart disease in men having previously suffered from heart attacks, and may cause allergy.
  • Half lives have been indicated for certain molecules.
  • the half lives of molecules can vary from these, e.g. generally based on the herb growing and/or preparation conditions, how it is combined with other herbs of molecules in treatment, or based on patient characteristics and behaviors such as eating and drinking and physical activity, or on potency or other factors. Doses and dose periods may be determined based in part on the half lives. Typically, however, doses and dose periods will be determined based on characteristics of the patient, the patient's condition and the patient's history, as well as on the expertise and experience of the attending physician.
  • a treatment method in accordance with certain embodiments may include administering periodic doses methotrexate, and/or another known treatment regimen described herein or as understood by those skilled in the art, along with an herbal combination of one or more herbs described herein, for treating a patient with psoriasis, eczema, melanoma, inflammation or a form of cancer that is known to be effectively treated with methotrexate such as cancer of the breast, skin, head and neck, or lung or rheumatoid arthritis, psoriasis or leukemia.
  • a treatment method in accordance with certain embodiments may include administering periodic doses of Pemetrexed, Pralatrexate, Methotrexate sodium, Pemetrexed Disodium or a folate analog metabolic inhibitor, alone or in combination with methotrexate, and/or another known treatment regimen described herein or as understood by those skilled in the art, along with an herbal combination of one or more of Da Huang, Sheng Di Huang, and Jin Yin Hua, and/or one or more of the other herbs described herein, for treating a patient with psoriasis, eczema, melanoma, inflammation or another inflammatory or autoimmune disease or form of cancer that is known to be effectively treated with methotrexate such as cancer of the breast, skin, bladder, head and neck, or lung, osteosarcoma, lymphoma, or trophoblastic neoplasms, or inflammation, or an autoimmune disease such as rheumatoid arthritis, juvenile dermatomyositis, psori
  • a treatment method in accordance with certain embodiments may include administering periodic doses of an herbal combination of one or more of Da Huang, Sheng Di Huang, and Jin Yin Hua, along with one or more of a class of drugs that are specifically understood for their effectiveness at treating auto immune diseases and/or for curbing bodily rejections after implantation or
  • lymphocytes including drugs that influence lymphocytes such as Azathioprine, Mycophenolate mofetil, Methotrexate and/or Cyclophosphoamide, and/or durgs that slow down meiosis of lymphocytes such as Cyclosporine, Tacrolimus, Sirolimus (Rapamycin) and/or drugs that neutralize cytokines such as Infliximab, Etanercept, Adalimunab and/or Anikra.
  • drugs that influence lymphocytes such as Azathioprine, Mycophenolate mofetil, Methotrexate and/or Cyclophosphoamide, and/or durgs that slow down meiosis of lymphocytes such as Cyclosporine, Tacrolimus, Sirolimus (Rapamycin) and/or drugs that neutralize cytokines such as Infliximab, Etanercept, Adalimunab and/or Anikra.
  • a treatment regimen may also include methotrexate and one or more of the herbs described herein in combination with approximately 5ug/ml or 10 ug/ml or more of emodin, alone or in combination with respectively 0.05 ug/ml or 0.10 ug/ml or more of digoxin and/or in before, during and/or after administration of a methotrexate treatment regimen and/or a regimen with another known treatment such as those described herein or that may be understood by those skilled in the art.
  • emodin alone or with at least approximately 0.10 ug/ml digoxin, or at least approximately lOug/ml emodin, alone or with at least approximately 0.10 ug/ml digoxin, or more than 5ug/ml of emodin, alone or with at least approximately 0.05 ug/ml digoxin, or at least approximately lOug/ml emodin, alone or with at least approximately 0.05 ug/ml digoxin.
  • Other combinations may be used and prescribed by physicians depending on factors such variances in weight, age, gender, family or patient history, or other characteristics specific to patients.
  • the treatment regimen may include once or twice daily doses, or two or more weekly doses weekly or otherwise. Doses may be taken more than once or twice a day, while the amounts of each dose would be determined according to the periodicity of the treatments.
  • Methods of preparing treatment medicines for psoriasis, eczema, melanoma, inflammation, leukemia or other cancer and/or an autoimmune disorder are also provided, including preparing a medicinal composition including methotrexate, or another known treatment described herein, and an herbal combination of one or more of Sheng Di Huang, Da Huang, Jin Yin Hua, or one or more of the other herbs described herein and/or one or more molecules, molecular extracts or molecular compounds described herein.
  • Treatments described herein may be prepared for topical use for treatment of melanoma, eczema, dermatisis, BCC (basal cyr carcinoma) and inflammatory skin diseases like Psoriasis.
  • combinations of herbs and/or herbal extracts as described herein may be prepared as a cream to apply onto the skin.
  • Methotrexate may be included or may be administered separately before, during or after the herbal treatment.
  • Methotrexate along with herbal combinations and/or herbal extract combinations described herein may be injected to infected areas of the skin of a patient using a syringe.
  • An example method for preparation of an external cream in accordance with certain embodiments is provided below.
  • a cream is then prepared that may be somewhat more of less than half herbs and half cream, e.g., a 30% liquid of herbs in 1 : 1 ratio and 70 % cream may be used.
  • the herbs can also be prepared as a tincture, e.g., soaking the herbs in alcohol for a period of time such as 2 weeks in a ratio of 1 :3, for example.
  • This herbal liquid can then be mixed with the cream in the same way as described above.
  • Treatments described herein may also be effective against immunodeficiency diseases such as HIV and AIDS, as well as other conditions affecting or caused by disorders of the immune system.
  • Herbal combinations of one or more of Da Huang, Sheng Di Huang and Jin Yin Hua and/or one or more other herbs or molecules described herein may be administered as a nutritional supplement or as a supplement to an exercise regimen or as an energy supplement or as a pain relief supplement or as a diuretic or sleep aid.
  • NSAIDs such as ibuprofen, naproxen and aspirin, other non-steroidal antiinflammatories, acetaminophen, and/or steroidal anti-inflammatories may be combined with an herbal combination of one or more of Da Huang, Sheng Di Huang and Jin Yin Hua and/or one or more other herbs or molecules described herein, with or without treatment with methotrexate before, during or after the herbal treatment, to treat inflammation or other ailments that are commonly treatable with NSAIDs, including chronic pain.
  • Formulations may be prepared for oral or topical administration as long release, lipidized dosage compositions or as short release non-lipidized formulas.
  • Certain embodiments are directed to advantageous medicines and methods of treatment and preparation of medicines and treatments for psoriasis, eczema, melanoma or other skin ailments, inflammation, autoimmune disease, leukemia or another form of cancer wherein combinations of methotrexate and/or another known treatment described herein with an herbal combination such as Da Huang and Sheng Di Huang, or Da Huang, sheng Di Huang and Jin Yin Hua, and/or one or more of Mu Dan Pi, Di Gu Pi, Xian He Cao and/or Chun Gen Pi, and/or any one or more of the following eleven additional herbs including Zi Cao, or radix arnebiae (arnebia root) or radix lithospermi
  • Methotrexate or another known treatment described herein may be combined with certain herbal ingredients, such as digoxin "D” and/or emodin "E,” and/or one or more others described above including Emodin, Rhein, and/or Rhapontin of Da Huang, Carvacrol, Vanillic acid, and/or Sitosterol of Jin Yin Hua, and/or Aucubin, Digoxin, and/or beta-sitosterol of Sheng Di Huang and/or other ingredients present within the two, the three, the seven and/or even the eighteen herbs, are used to inhibit tumor cell growth and/or reduce white cell count.
  • certain herbal ingredients such as digoxin "D” and/or emodin "E,” and/or one or more others described above including Emodin, Rhein, and/or Rhapontin of Da Huang, Carvacrol, Vanillic acid, and/or Sitosterol of Jin Yin Hua, and/or Aucubin, Digoxin, and/or beta-sitosterol of Sheng Di
  • Methotrexate or another known treatment described herein may be combined both with an herbal combination of one or more of the herbs described herein and one or more molecules, molecular extracts or herbal ingredients described herein.
  • the methotrexate or other known treatment may be administered before, during and/or after administration of the herbal and/or molecular treatment, and these may be administered together or separately, at the same time or temporally spaced apart in accordance with various embodiments.
  • herbal combinations may include doses of between 13.3 grams to 120 grams of Sheng Di Huang, or 3.3 grams to 60 grams of Da Huang, or both, alone or together, or in combination with one of more of the other herbs, and/or in combination with additional emodin or digoxin or another molecule described herein, or combinations thereof.
  • the herbal combinations may be administered daily or 2-3 times daily before meals or up to lOx daily or less than daily even as little as three times a month, and the herbal combinations may be administered before, during and/or after a methotrexate dosage administration or regimen.
  • Any of Da Huang, Sheng Di Huang and Jin Yin Hua may be administered as a single herb complement or supplement along with a methotrexate regimen.
  • any two of these herbs, or all three of them, may also be combined and administered as a supplement or complement to a methotrexate regimen.
  • the regimen described includes 3.3 grams to 60 grams of Jin Yin Hua.
  • one or more molecules, molecular extracts and/or molecular compounds are included in the regimen.
  • one, two, three or all four of the herbs Mu Dan Pi, Xian He Cao, Chun Gen Pi and Di Gu Pi is/are combined with one, two or all of the three herbs Sheng Di Huang, Da Huang and Jin Yin Hua, including 3.3 grams to 15 grams of any of the other four of the seven herbs, e.g., 3.3 grams to 15 grams of Mu Dan Pi, 3.3-10 grams to 15 grams of Xian He Cao, 3.3-10 grams to 15 grams of Chun Gen Pi, and/or 3.3-5 grams to 15 grams of Di Gu Pi.
  • 40 grams of Sheng Di Huang in 100 grams of water, 15 grams of Da Huang in 60 grams of water and 15 grams of Jin Yin Hua in 60 grams of water may be combined in a single treatment dosage and administered to a patent.
  • the combination may be cooked once or twice, and the herb: liquid ratio may be 1 : 10 or otherwise, and the herbs may be prepared in multiple ways, including as dry, aqueous or lipidized components.
  • the dose may be 1-10 days or even multiple times daily including 2-6 times daily, and even as often as 10 times daily.
  • a treatment regimen includes a combination of methotrexate with one or more of the following seven herbs, such as 5 grams of Mu Dan Pi in 15 grams of water, 20 grams of Sheng Di Huang in 80 grams of water, 5 grams of Xian He Cao in 15 grams of water, 5 grams of Chun Gen Pi in 15 grams of water, 5 grams of Di Gu Pi in 15 grams of water, 10 grams of Da Huang in 40 grams of water and 10 grams of Jin Yin Hua in 40 grams of water.
  • the combination may be cooked once or twice, and the herb: liquid ratio may be 1 : 10 or otherwise, and the herbs may be prepared in multiple ways, including as dry, aqueous or lipidized components.
  • the dose may be 1-10 days or even multiple times daily including 2-6 times daily, and even as often as 10 times daily.
  • a low dose formula includes a methotrexate regimen along with lug/ml or more of emodin or 0.05ug/ml or more of digoxin, or both, and/or 3.3 grams or more of one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, and/or one or more of the following eighteen herbs includes 3.3 grams of Da Huang in about 32 grams water, 13.3 grams of Sheng Di Huang in about 129 grams of water, 3.3 grams of Jin Yin Hua in about 32 grams of water, 3.3 grams of Mu Dan Pi in about 32 grams of water, 5 grams of Di Gu Pi in about 48 grams of water, 10 grams of Xian He Cao in about 97 grams of water, 10 grams of Chun Gen Pi in about 97 grams of water, 8.3 grams of Zi Cao in about 80 grams of water, 6.7 grams of Xuan Shen in about 65 grams of water, 3.3 grams of Shi Gao in about 32 grams of water, 4 grams of Bai Shao in about 39 grams of water,
  • a high dose formula includes a methotrexate regimen along with 5ug/ml or more of emodin or 0. lug/ml or more of digoxin, or both, and/or 15 grams or more of one or more of Da Huang, Sheng Di Huang and Jin Yin Hua, and/or one or more of the following eighteen herbs: 30 grams of Da Huang in about 300 grams water, 60 grams of Sheng Di Huang in about 600 grams of water, 30 grams of Jin Yin Hua in about 300 grams of water, 15 grams of Mu Dan Pi in about 150 grams of water, 15 grams of Di Gu Pi in about 150 grams of water, 15 grams of Xian He Cao in about 150 grams of water, 15 grams of Chun Gen Pi in about 150 grams of water, 5 grams of Zi Cao in about 50 grams of water, 5 grams of Xuan Shen in about 50 grams of water, 5 grams of Shi Gao in about 50 grams of water, 5 grams of Bai Shao in about 50 grams of water, 5 grams of Chi Shao in about 50 grams of water, 5
  • a methotrexate regimen is supplemented by a low dose herbal formula including 3.3 grams of two or more of Da Huang, Sheng Di Huang and Jin Yin Hua, and/or one or more of the following seven herbs: 3.3 grams of Da Huang, 13.3 grams of Sheng Di Huang, 3.3 grams of Jin Yin Hua, 3.3 grams of Mu Dan Pi, 5 grams of Di Gu Pi, 10 grams of Xian He Cao, and 10 grams of Chun Gen Pi in water or in a dry or a lipidized formulation or otherwise configured for topical, oral, intravenous or sub-dermal injectable administration.
  • a low dose herbal formula including 3.3 grams of two or more of Da Huang, Sheng Di Huang and Jin Yin Hua, and/or one or more of the following seven herbs: 3.3 grams of Da Huang, 13.3 grams of Sheng Di Huang, 3.3 grams of Jin Yin Hua, 3.3 grams of Mu Dan Pi, 5 grams of Di Gu Pi, 10 grams of Xian He Cao, and 10 grams of Chun
  • a methotrexate regimen is supplemented by a high dose herbal formula including 30 grams or more of Da Huang, and/or with one or more of the following seven herbs: 60 grams of Sheng Di Huang, 30 grams of Jin Yin Hua, 15 grams of Mu Dan Pi, 15 grams of Di Gu Pi, 15 grams of Xian He Cao, and 15 grams of Chun Gen Pi, in water or in a dry or a lipidized formulation or otherwise configured for topical, oral, intravenous or sub-dermal injectable administration.
  • a high dose herbal formula including 30 grams or more of Da Huang, and/or with one or more of the following seven herbs: 60 grams of Sheng Di Huang, 30 grams of Jin Yin Hua, 15 grams of Mu Dan Pi, 15 grams of Di Gu Pi, 15 grams of Xian He Cao, and 15 grams of Chun Gen Pi, in water or in a dry or a lipidized formulation or otherwise configured for topical, oral, intravenous or sub-dermal injectable administration.
  • a methotrexate regimen is supplemented with a low dose formula including the three herbs including 3.3-20 grams of Da Huang, 10-60 grams of Sheng Di Huang, and 3.3-20 grams of Jin Yin Hua.
  • a methotrexate regimen is supplemented with a low dose formula including 3.3-20 grams of Da Huang and 10-60 grams of Sheng Di Huang.
  • a methotrexate regimen is supplemented with a low dose formula including 3.3-20 grams of Jin Yin Hua and 10-60 grams of Sheng Di Huang.
  • a methotrexate regimen is supplemented with a low dose formula including 3.3-20 grams of Da Huang and 3.3-20 grams of Jin Yin Hua.
  • a methotrexate regimen is supplemented with a low dose formula including the one herb including 3.3-30 grams of Da Huang.
  • a methotrexate regimen is supplemented with a low dose formula including the one herb including 3.3-30 grams of Jin Yin Hua.
  • a methotrexate regimen is supplemented with a low dose formula including the one herb including 10-90 grams of Sheng Di Huang.
  • a methotrexate regimen is supplemented with a medium dose formula including the three herbs including 10-100 grams of Da Huang, 25-250 grams of Sheng Di Huang, and 10-100 grams of Jin Yin Hua.
  • a methotrexate regimen is supplemented with a medium dose formula including 10-100 grams of Da Huang and 25-250 grams of Sheng Di Huang.
  • a methotrexate regimen is supplemented with a medium dose formula including 10-100 grams of Jin Yin Hua and 25-250 grams of Sheng Di Huang.
  • a methotrexate regimen is supplemented with a medium dose formula including 10-100 grams of Da Huang and 10-100 grams of Jin Yin Hua.
  • a methotrexate regimen is supplemented with a medium dose formula including the one herb including 10-100 grams of Da Huang.
  • a methotrexate regimen is supplemented with a medium dose formula including the one herb including 10-100 grams of Jin Yin Hua.
  • a methotrexate regimen is supplemented with a medium dose formula including the one herb including 25-250 grams of Sheng Di Huang.
  • a methotrexate regimen is supplemented with a high dose formula that includes 30-300 grams of Da Huang, 60-600 grams of Sheng Di Huang, and 30-300 grams of Jin Yin Hua.
  • a methotrexate regimen is supplemented with a high dose formula that includes 30-300 grams of Da Huang, and 60-600 grams of Sheng Di Huang.
  • a methotrexate regimen is supplemented with a high dose formula that includes 30-300 grams of Da Huang and 30-300 grams of Jin Yin Hua.
  • a methotrexate regimen is supplemented with a high dose formula that includes 60-600 grams of Sheng Di Huang and 30-300 grams of Jin Yin Hua.
  • a methotrexate regimen is supplemented with a high dose formula that includes 30-300 grams of Da Huang.
  • a methotrexate regimen is supplemented with a high dose formula that includes 30-300 grams of Jin Yin Hua.
  • a methotrexate regimen is supplemented with a high dose formula that includes 60-600 grams of Sheng Di Huang.
  • a methotrexate regiment is supplemented with a medium dose herbal formula that includes 10 grams of Da Huang in about 100 grams water, or in dry or lipidized form for oral, topical, sub-dermal or IV administration.
  • a methotrexate regiment is supplemented with a medium dose herbal formula that includes 25 grams of Sheng Di Huang in about 250 grams of water, or in dry or lipidized form for oral, topical, sub-dermal or IV administration.
  • a methotrexate regimen is supplemented with a medium dose herbal formula that includes 10 grams of Jin Yin Hua in about 100 grams of water, or in dry or lipidized form for oral, topical, sub-dermal or IV administration.
  • a methotrexate regimen is supplemented with a medium dose herbal formula that includes 20 grams of Da Huang, 40 grams of Sheng Di Huang, and 20 grams of Jin Yin Hua in about 400 grams of water or more, or in dry or lipidized form for oral, topical, sub-dermal or IV administration.
  • a medium dose herbal formula that includes 20 grams of Da Huang, 40 grams of Sheng Di Huang, and 20 grams of Jin Yin Hua in about 400 grams of water or more, or in dry or lipidized form for oral, topical, sub-dermal or IV administration.
  • a methotrexate regimen is supplemented with a medium dose formula that includes 15 grams of Da Huang, 35 grams of Sheng Di Huang, and 15 grams of Jin Yin Hua in about 300 grams of water or more, or in dry or lipidized form for oral, topical, sub-dermal or IV
  • a methotrexate regiment is supplemented with an herbal combination that includes 25-75 grams of Da Huang, 45-135 grams of Sheng Di Huang, and 25-75 grams of Jin Yin Hua in about 250-750 grams of water, or in dry or lipidized form for oral, topical, sub-dermal or IV administration.
  • a methotrexate regimen is supplemented with a low dose herbal formula that includes 3.3-10 grams of Da Huang, and 13.3-40 grams of Sheng Di Huang in about 100-300 grams of water, or in dry or lipidized form for oral, topical, sub-dermal or IV administration.
  • a methotrexate regimen is supplemented with a high dose herbal formula that includes 30-100 grams of Da Huang and 60-200 grams of Sheng Di Huang in about 600-6000 grams of water, or in dry or lipidized form for oral, topical, sub-dermal or IV administration.
  • a methotrexate regimen is supplemented with a medium dose herbal formula that includes 10-50 grams of Da Huang and 30-150 grams of Sheng Di Huang in about 400- 2000 grams of water, or in dry or lipidized form for oral, topical, sub-dermal or IV administration.
  • a methotrexate regimen is supplemented with a medium dose herbal formula that includes 20-50 grams of Da Huang and 40-100 grams of Sheng Di Huang in about 600- 5000 grams of water, or in dry or lipidized form for oral, topical, sub-dermal or IV administration.
  • a methotrexate regimen is supplemented with a medium dose herbal formula that includes 15-100 grams of Da Huang and 45-300 grams of Sheng Di Huang in about 600- 4000 grams of water, or in dry or lipidized form for oral, topical, sub-dermal or IV administration.
  • a methotrexate regimen is supplemented with a medium dose herbal formula that includes 25-75 grams of Da Huang in about 300 grams water, and 50-150 grams of Sheng Di Huang in about 500 grams of water, or in dry or lipidized form for oral, topical, sub-dermal or IV administration.
  • Examples of low, medium and high dose herbal formulas for supplementing a methotrexate regimen before, during or after administration of said methotrexate regimen include one or more of the other herbs described herein, such as any of herbs contained in the seven herb and eighteen herb combinations described herein, that are administered in doses that are the same as or similar to or commensurate with the low, medium and high dose example formulas for the one, two and three herb combinations described above, including corresponding percentage changes when four or more herbs are included in the supplemental herbal formula that is administered before during or after a methotrexate dose or regimen. Many other combinations may be used depending on characteristics of the patient such as age and weight, the condition of the patient, and the patient's history.
  • Doses in between the low dose and high dose examples for the formulas that include one, two, or three or more herbs, or the seven herb formula, or the eighteen herb formula are also within the scope of further examples with per herb doses and/or total herb doses that are within the ranges provided in the examples above.
  • doses above the high dose formula or below the low dose formula may be used as determined by a physician using his or her expertise and experience both generally in the field and with specific patients.
  • other combinations of two, three, four, five, or more of these 18 herbs, and/or including one or more other herbs as understood by those skilled in the art may be used in further examples of formulas wherein the dose ranges described in the above examples or otherwise as determined by a physician may be used.
  • CXCR4 antagonists significantly inhibited the growth of leukemic cells at concentrations between (0.05-to 1 microgram/ml). Emodin by itself inhibited the growth of leukemic cells only at concentrations of more than 5microgrm/ml.
  • emodin may be extracted from traditional medicinal plants such as Rhei Rhizoma and Rheum Palmatum.
  • the source of Emodin used is Da Huang-Chinese name, or Rhubarb Root-English name, or Rheum Plamatum-Botanical name, or Radix Rhisoma Rhei-Pharmaceutical name.
  • Emodin may be extracted from Rhubarb, Buckthorn and/or Japanese Knotweed (Fallopia Japonica).
  • Aloe-emodin may be used which is a variety of emodin found in Socotrine, Barbados, and Zanzibar aloes.
  • a medicinal treatment is prepared in certain embodiments by mixing the herb, Da Huang, in water at a ratio of approximately 10: 1.
  • the herb may be ground to a fine powder.
  • the water may be added to the fine powdered herb, and the pot covered.
  • the heat is lowered in certain embodiments to about 70 degrees centigrade.
  • the aqueous mixture is cooked for another hour.
  • the liquid is then strained into a container. In some cases, this may be done twice.
  • the ratio may be reduced to 7.5 : 1.
  • the second cooking may take about 45 minutes including the boiling.
  • Other herbs including Sheng Di Huang and/or Jin Yin Hua may be mixed with the Da Huang or prepared alone or in combination with other herbs.
  • Dry or lipidized capsules, or a cream, or a topical injection solution, or an IV solution, or other formulations understood to those skilled in the art may also be provided for administration of the treatment.
  • the methotrexate or other known or described treatment that is administered before during and/or after the herbal medicinal treatment in accordance with certain embodiments may also be prepared in multiple ways as understood by those skilled in the art.
  • Single herbs or combinations of two or more herbs alone or with any one or more of the described molecules may be prepared in a process involving the following or a subset or variation thereof: grinding the herbs to a fine texture in the mixer for around 2-3 min until it looked fine powder; weighing the powder (e.g., 25 gm) and transferring to a beaker (e.g., 2000 ml); adding distilled water (RT) to powdered herbs in a ratio of 1 :20 (gm of herbs: ml of water) and soaking the herbs for 15-20 min; boiling the mixture to 85-90° C; cooling the temperature of the mixture down to 70-75C after removing it from the hot plate; covering the beaker properly with aluminum paper and cooking the mixture at 70°C on hot plate -the total time of cooking of the mixture may be approximately 60 min which includes boiling, cooling it down and cooking; straining the mixture with the help of a manual strainer; after filtration, centrifuging the extract at 5000 rpm for 15 min and collecting the supernatant
  • a source of Digoxin in certain embodiments is Sheng Di Huang-Chinese name, or Foxglove root-English name, or Radix Rhemania-Pharmaceutical name.
  • the preparation of the Digoxin may be the same as for the Emodin.
  • the herbs from which the Emodin and Digoxin are extracted are cooked together.
  • Digoxin may be extracted from Digitalis Purpurea or Purple Foxglove.
  • a prepared treatment may not be "pure.”
  • certain treatments may involve a "vegetable soup” type regiment made of more than one and even two, three, seven or eighteen herbal ingredients per specific examples provided herein, or any combinations of the herbs described herein, or combinations of the herbs described herein with other herbs not mentioned herein.
  • herbal ingredients are mixed in solution and a patient may drink the liquid. While freeze-drying the herb in powder form may be possible, the above-described process appears to be more effective.
  • NB4 AML
  • HL60 and Jurkat were seeded at 2xl0 5 viable cells/ 1 ml per well into a 24-well plate in triplicates in a medium supplemented with 10 % FCS and incubated with different concentrations of digoxin, Emodin, and their combination for 24 hours. Following the incubation, the cells were stained with propidium iodide (PI) (Sigma, St. Louis, MO) and percent of viable Pi-negative cells in culture was determined by FACScalibur analysis (Becton Dickinson Immunocytometry Systems), using CellQuest software.
  • PI propidium iodide
  • Adherent prostate cancer PC3 cells and colon cancer HT29 cells were seeded at lxl 0 5 viable cells/1 ml per well into a 24-well plate under conditions described above, and following 24-hour exposure to digoxin, Emodin, and their combination, the cells were harvested, washed with PBS and stained with PI and counted as described for hematopoietic cells.
  • CLL Chronic Lymphocytic Leukemia
  • a treatment regimen that includes methotrexate along with periodic doses of an advantageous herbal combination, is provided to treat psoriasis, eczema, melanoma or other skin disease, inflammation, autoimmune disorder, and/or cancer.
  • the herbal combination may include in certain embodiments Jin Yin Hua, Sheng Di Huang and Da Huang, otherwise referred to herein as the three herb combination or "3HX.”.
  • Another treatment regimen includes methotrexate and one or more of emodin and digoxin and/or another of the molecules described herein, and/or one or more of Jin Yin Hua, Sheng Di Huang and Da Huang, and/or one or more of Mu Dan Pi, Di Gu Pi, Xian He Cao and Chun Gen Pi.
  • the treatment regimen may be administered topically, orally, subcutaneously and/or intravenously, and the methotrexate may be administered before, during and/or after administration of the herbal combination.
  • Figures 1-32B illustrate results of studies of methotrexate and betamethasone combinations with certain herbs, namely Da Huang, Sheng Di Huang and Jin Yin Hua (3HX), administered to lab animals.
  • the study involved both in-vitro and in-vivo investigations.
  • betamethasone between 0.01 and 150 ⁇ .
  • 20 uL of TP A were administered along with 20uL of 3HX in topical formulations and/or with 500mg/kg or lOOOmg/kg in oral dosage administrations.
  • a TP A control included 20uL TP A + 0.25%NA-CMC.
  • the data tabulated in Figures 1 and 2 illustrate synergistic effects of combination treatments of 3HX and methotrexate & betamethasone in human keratinocytes (hacat) in vitro.
  • Figure 1 includes a table illustrating an inhibitory effect of a medicinal composition including an herbal combination of Sheng Di Huang, Da Huang and Jin Yin Hua (3HX) and methotrexate (hereinafter in many places "MTX”) in accordance with certain embodiments on proliferation of HaCaT cells.
  • a medicinal composition including an herbal combination of Sheng Di Huang, Da Huang and Jin Yin Hua (3HX) and methotrexate (hereinafter in many places "MTX”) in accordance with certain embodiments on proliferation of HaCaT cells.
  • Figure 2 includes a table illustrating an inhibitory effect of a medicinal composition including an herbal combination of Sheng Di Huang, Da Huang and Jin Yin Hua (hereinafter in many places “3HX”) and betamethasone (hereinafter "BD”) in accordance with certain embodiments on proliferation of HaCaT cells.
  • a medicinal composition including an herbal combination of Sheng Di Huang, Da Huang and Jin Yin Hua (hereinafter in many places “3HX”) and betamethasone (hereinafter “BD”) in accordance with certain embodiments on proliferation of HaCaT cells.
  • Figures 3A-3B include plots of data illustrating effects of 3HX treatments in accordance with certain embodiments on 12-0-tetradecanoylphorbol- 13 -acetate (hereinafter "TPA") induced ear inflammation and ear thickness changes in lab animals, respectively.
  • TPA 12-0-tetradecanoylphorbol- 13 -acetate
  • FIG. 3A topical application of low concentration of 3HX (1 :8) and oral treatment of high dose (lOOOmg/kg) of 3HX rendered advantageous reduction in absolute ear thickness of the lab animals.
  • Figures 4A-4B include bar charts of data illustrating effects of 3HX treatments in accordance with certain embodiments on TPA-induced psoriasis based upon ear punch biopsy weight and epidermal ear thickness in lab animals, respectively.
  • 3HX treatment groups significant reduction in punch biopsy weight was obtained when high doses were topically administered to lab animals.
  • Epidermal ear thickness was calculated from histopathological section photographs.
  • Topical application of 3HX were found to exert advantageous effects on TPA induced increase in epidermal ear thickness.
  • a marked reduction in hyperkeratosis, ear edema and inflammatory cell infiltration was observed in the 3HX treatment groups when compared with those of the TPA control group.
  • oral (500mg/kg) and topical (1 :4) treatment of 3HX profoundly inhibited TPA induced cell proliferation.
  • Figures 5A-5B include bar charts of data illustrating % inhibitory activity and effect on serum nitric oxide level, respectively, of oral and topical 3HX treatments in accordance with certain embodiments.
  • Oral application of 3HX exerted marginal inhibitory activity against TPA induced ear inflammation in mice.
  • Oral administration of 3HX partially inhibited the generation of nitric oxide content against TPA induced mice inflammation, a biochemical marker for inflammation.
  • Topical and oral treatment with 3HX exerted only a small effect over suppression of enzyme myeloperoxidase activity which is commonly used as an index of granulocyte infiltration in the chronic inflammation model and body weight change.
  • 3HX, MTX and BD and combinations of 3HX with MTX and of 3HX with BD were evaluated as treatments for TPA induced psoriasis in lab animals. Particular attention was paid to the TPA induced ear inflammation model in mice. Doses of 20uL TPA, 20uL of 0.05% topical 3HX and 500mg/kg oral 3HX, 0.5mg/kg MTX and 20uL of 0.05% topical BD were administered to the lab animals. Topical and oral administrations of 3HX were studied, along with oral administration of MTX and topical administration of BD.
  • a control group included 20uL TPA + 20uL solvent + lOml/kg of 0.25% Na-CMC.
  • Figures 6A-6B include plots of data illustrating effects on TPA-induced psoriasis based upon ear thickness changes in lab animals of treatments with 3HX and MTX and 3HX and BD, respectively, in accordance with certain embodiments.
  • Figure 6C includes plots of data illustrating effects of 3HX, MTX and BD treatments in accordance with certain embodiments on TPA-induced psoriasis based upon absolute ear thickness in lab animals.
  • mice treated with betamethasone alone as well as animals treated with betamethasone and 3HX in combination has shown high reduction in absolute ear thickness and ear thickness change.
  • Figure 7A includes bar charts of data illustrating % inhibition of ear inflammation in lab animals of MTX alone and in combination with 3HX in accordance with certain embodiments.
  • Figure 7B includes bar charts of data illustrating % inhibition of ear inflammation in lab animals of BD alone and in combination with 3HX in accordance with certain embodiments.
  • Figure 7C includes a bar chart of data illustrating effects of drug treatments in accordance with certain embodiments on ear biopsy weight of lab animals.
  • mice treated with methotrexate (MTX) alone showed considerable decrease in ear edema (41.87%) as compare to TPA control on day 6, confirming the effectiveness of MTX alone that may already be understood by those skilled in the art.
  • animals treated with a combination of MTX (0.5mg/kg) & 3HX 500 mg/kg (1 :4) showed prominent inhibition of ear edema (56.62%) that is 15% above that found for MTX alone, confirming a synergistic effect of this combination.
  • Animals treated with betamethasone (BD) alone and in combination with 3HX showed high decrease in ear punch biopsy weight as compared to the TPA control.
  • animals treated with 3HX 500 mg/kg & (1 :4) also showed a significant decrease in ear punch biopsy weight, evidencing effectiveness of administering 3HX in treating psoriasis.
  • Figure 8 includes a bar chart of data illustrating effects of various treatments in accordance with certain embodiments on TPA-induced psoriasis based upon epidermal ear thickness in lab animals. Marked reduction in hyperkeratosis and ear edema was observed in groups treated with BD and MTX alone, as expected, while combinations of 3HX and BD and 3HX and MTX also showed marked reduction in hyperkeratosis and ear edema. Epidermal ear thickness results are also in accordance with the histopatho logical observations where significant (P ⁇ 0.01) reduction was observed for treatments with a combination of 3HX and MTX, and also for MTX and BD alone treatments compared with the TPA control. In immunohistochemical findings, oral treatment with a combination of MTX and 3HX, including oral and topical treatment with 3HX in combination with oral
  • Figure 9A-9B include plots of data illustrating effects of MTX and BD on TPA induced psoriasis based upon absolute ear thickness and ear thickness change in lab animals, respectively.
  • Figure 10 includes a table of data illustrating % inhibitory activity of MTX and BD on TPA- induced psoriasis based upon ear thickness in lab animals.
  • Figures 11A includes a bar charts of data illustrating effects of MTX and BD on TPA induced psoriasis based upon ear punch biopsy weight of lab animals.
  • Figure 1 IB includes a bar chart of data illustrating % inhibition of drug treatment on TPA- induced psoriasis based upon ear biopsy weight of lab animals.
  • Figure 12 includes a table of treatments, doses, regimens, volumes and routes in accordance with certain embodiments.
  • Figures 13A-13C include bar charts of data illustrating effects of treatments in accordance with certain embodiments on TPA-induced psoriasis based upon changes in ear thickness of lab animals.
  • Co-administration of oral 3HX (500 mg/kg) with topical 3HX cream (5.0%) and combination treatment of oral 3HX (500mg/kg) with topical 3HX (1 :4) showed better anti-inflammatory effect as compared to other treated groups (particularly on the 6th day of treatment, when disease induction reaches its peak).
  • Figure 14A includes a table of data illustrating % inhibition of treatments in accordance with certain embodiments on TPA-induced psoriasis.
  • Figure 14B includes a bar chart of data illustrating % inhibitory activity of various treatments in accordance with certain embodiments on TPA-induced psoriasis.
  • Figures 15A-15C include bar charts of data illustrating effects of topical and oral treatments in accordance with certain embodiments on TPA-induced psoriasis based upon ear thickness in lab animals.
  • oral-topical treatment with 500mg/kg 3HX and 2.5% 3HX cream exhibited high reduction in ear thickness and the effect was found to be better than the individual treatment, suggesting an enhanced effect of treating with both.
  • Figures 16A-16C include bar charts of data illustrating TNF-a levels in ear tissues of lab animals upon 3HX, MTX and BD treatments in accordance with certain embodiments.
  • Significant reduction in TNF-a levels in ear tissue homogenate was observed in lab animals treated with 2.5% 3HX cream and in 1 :4-3HX treatment groups.
  • Oral-topical combination of 3HX 500mg/kg + 5.0% cream) showed best results among all the oral and topical cream 3HX treatment groups, clearly indicating an advantageous feature of administering both the oral and topical formulations of 3HX.
  • Figures 17A-17C include bar charts of data illustrating effects of topical and oral 3HX, MTX and BD treatments in accordance with certain embodiments on IL-6 levels in ear homogenate of lab animals.
  • 2.5% 3HX cream exhibited significantly (p ⁇ 0.05) better effect than 5.0% 3HX cream as well as standard BD.
  • Significant reduction in IL-6 levels were observed for oral- topical combination of 3HX powder and 3HX cream, which were also better than standard BD and MTX treatments.
  • Figure 18 includes a table illustrating 3HX, MTX, BD and Da Huang alone (hereinafter “1HX”) treatments, doses, regimens, volumes and routes in accordance with certain embodiments.
  • 1HX Da Huang alone
  • Figures 19A-19B includes plots of data illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on imiquimod (hereinafter "IMQ")-induced psoriasis based upon absolute ear thickness of lab animals.
  • IMQ imiquimod
  • Minimal disease induction was obtained in disease control formulation placebo due to the anti-psoriatic potential of placebo cream constituents.
  • Topical application of 2.5% and 5.0% 3HX cream showed significant reduction in absolute ear thickness on Day 9 (P ⁇ 0.01 for 2.5% and P ⁇ 0.05 for 5.0%>).
  • Figure 20 includes a table illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on % inhibitory activity of IMQ-induced psoriasis based upon ear thickness of lab animals.
  • Figures 21A-21B include bar charts of data illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on IMQ-induced psoriasis based upon ear punch biopsy weights of lab animals.
  • Topical application of 2.5% 3HX cream exerted significant reduction in ear punch biopsy weight.
  • No dose dependant response was observed among the three tested oral doses of 3HX with low dose (500mg/kg) medium dose (lOOOmg/kg) and high dose (1500mg/kg) each showing a similarly significant effect.
  • 1HX, or treatment with Da Huang produced a significant reduction of punch biopsy weight which is comparable to standard BD.
  • Figures 22A-22B includes bar charts of data illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on IMQ-induced psoriasis based upon ear thickness of lab animals.
  • Topical application of 2.5% 3HX cream resulted in significant reduction of ear thickness.
  • No dose dependent response was observed among the three tested oral doses of 3HX with low dose (500mg/kg) medium dose (lOOOmg/kg) and high dose (1500mg/kg) each showing a similarly significant effect.
  • 1HX, or treatment with Da Huang produced significant reduction of ear thickness.
  • Figures 23A-23B include bar charts of data illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on IL-17 levels in lab animals. No dose dependent response was observed among the three tested oral doses of 3HX. 1HX, or treatment with Da Huang, produced significant reduction of IL-17 level which is comparable to standard BD.
  • Figures 24A-24B include bar charts of data illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on IL-23 levels in lab animals.
  • Topical application of 5.0% 3HX cream produced the most reduction of IL-23 levels in ear tissue homogenate.
  • All the three tested oral doses of 3HX exhibited significant reduction of IL-23 levels in ear tissue homogenate. No dose dependent response was observed among the three doses 500mg/kg, lOOOmg/kg and
  • 1HX (Da Huang) produced significant reduction of IL-23 levels in ear tissue homogenate.
  • Figures 25A-25B includes bar charts of data illustrating effects of 3HX, MTX, BD and 1HX treatments in accordance with certain embodiments on IMQ-induced psoriasis in lab animals.
  • Topical application of either 2.5% or 5.0% 3HX cream showed no significant effect over cumulative psoriatic scoring. All the three tested oral doses of 3HX resulted in marginal reduction of cumulative psoriatic scoring. 1HX produced a highest reduction of cumulative psoriatic scoring among the tested groups.
  • Figure 26 includes a table illustrating 3HX, MTX, and BD treatments, doses, regimens, volumes and routes in accordance with certain embodiments.
  • Figures 27A-27C include bar charts of data illustrating effects of 3HX, MTX, and BD treatments in accordance with certain embodiments on IMQ-induced psoriasis based upon ear thickness of lab animals.
  • this combination effect was better than either 3HX cream or with standard MTX or BD alone, suggesting a advantageously synergistic effects of combining 3HX with MTX and with combining 3HX with BD.
  • Figure 28 includes a table illustrating effects of 3HX, MTX, and BD treatments in accordance with certain embodiments on % inhibitory activity of IMQ-induced psoriasis based upon ear thickness changes in lab animals.
  • Figures 29A-29C include bar charts of data illustrating effects of 3HX, MTX, and BD treatments in accordance with certain embodiments on IMQ-induced psoriasis based upon ear punch biopsy weights in lab animals.
  • a significant reduction in punch biopsy weight was found when lab animals were administered a combination of topical application of 2.5% 3HX cream with oral MTX (P ⁇ 0.05), and when 3HX was combined with topical BD, partial reduction was found, suggesting advantageously synergistic activity.
  • Oral treatment with 3HX resulted in marginal reduction in punch biopsy weight.
  • Oral 3HX in combination with oral MTX produced significant reduction in punch biopsy weight (P ⁇ 0.05).
  • Figures 30A-30C include plots of data illustrating effects of 3HX, MTX, and BD treatments in accordance with certain embodiments on IMQ-induced psoriasis in lab animals.
  • Topical application of 2.5% 3HX cream resulted in significant reduction of cumulative psoriatic score on Day 8 and Day 9 (P ⁇ 0.001).
  • Co-administration of topical 2.5% 3HX cream with oral MTX and topical BD also showed significant reduction of cumulative psoriatic score on Day 7 to Day 9.
  • Oral treatment with 3HX alone or in combination with MTX did not render as significant a reduction of cumulative psoriatic score as when 3HX cream was administered.
  • Figures 31A-31C include bar charts of data illustrating effects of 3HX, MTX, and BD treatments in accordance with certain embodiments on IL-17 levels in lab animals.
  • Administrations of 2.5% 3HX cream, 2.5% 3HX cream + MTX (3mg/kg) and 2.5% 3HX cream + BD (0.001%) were found to produce, respectively, -41.80%, 40.33%> and 48.67%> inhibitory activity, which further suggest an advantageous synergistic effect.
  • Oral treatment of 3HX either alone or in combination with 3HX did not exhibit significant inhibition of IL-17 levels with -33.25% and - 49.53% inhibitory activity, respectively .
  • Figures 32A-32B includes bar charts of data illustrating effects of 3HX, MTX, and BD treatments in accordance with certain embodiments on IL-23 levels in lab animals.
  • the 2.5% 3HX cream, the 2.5% 3HX cream + MTX and the 2.5% 3HX cream + BD were found to produce - 48.16%, 30.46% and 41.93% inhibitory activity respectively.
  • Oral treatment of 3HX either alone or in combination with 3HX cream did not produce significant inhibition of IL-23 levels with -53.07% and - 39.18% inhibitory activity respectively.
  • Oral treatment with MTX at the dose of 1 Omg/kg and 3mg/kg respectively showed 4.26% and -8.65% inhibitory activity.
  • Topical administration of BD at the concentrations of 0.01% and 0.001% exerted - 26.69% and 23.60% (P ⁇ 0.05) respectively.
  • Figures 33-48 illustrate results of psoriasis studies involving administration to lab animals of Da Huang, Sheng Di Huang and Jin Yin Hua, as well as emodin and digoxin.
  • Anti -psoriatic activity of 3-HX, and of D&E was determined in studies using 12-0- Tetradecanoylphorbol-13-Acetate (TP A) induced ear inflammation in male C57BL/6 mice. All the animals were randomized based upon the body weight and allotted to seven groups with 6 animals in each group. Groups Gl and G2 were treated topically with test item 3HX at the dose levels of 1 :4 and 1 :8 dilutions respectively.
  • Groups G3 and G4 were treated orally with test item 3HX at the dose levels of 500 and lOOOmg/kg respectively.
  • Group G5 and G6 were treated topically and orally with D and E respectively.
  • Group G7 served as both TPA control (right ear) and solvent control (left ear) and was treated orally with Na-CMC.
  • test item was not conducted as part of this study, and is the responsibility of the
  • mice Male C57BL/6 mice were selected as the test system, as they were commonly reported in literature to evaluate the effect of test item for anti-psoriatic potential on TPA induced ear inflammation model.
  • 5mg/ml stock of TPA was prepared in DMSO and aliquot of the same was diluted to 1 :50 with methanol to achieve final TPA concentration of 10( ⁇ g/ml for topical application.
  • 3-HX a stock solution of 100 mg/ml was prepared in distilled water and was further diluted to 50mg/mL, in-order to administer the dose of 500mg/kg and lOOOmg/kg.
  • required amount of 3HX was dissolved in DMSO to obtain the final dilution of 1 :4 and 1 :8.
  • test item D 10 mg/ml was prepared in DMSO and was further formulated with 0.25% Na-CMC to obtain final strength of O.
  • lmg/ml For topical application, required amount of D was dissolved in DMSO and methanol and stored at -20°C. Similarly, for oral application of test item E, lOmg/ml stock was prepared in 0.25% Na-CMC and 0.1 % Tween 80. For topical application, required amount of E was dissolved in DMSO and diluted with methanol.
  • Groups Gl and G2 were treated topically with test item 3HX at the dose levels of 1 :4 and 1 :8 dilutions respectively.
  • Groups G3 and G4 were treated orally with test item 3HX at the dose levels of 500 and lOOOmg/kg respectively.
  • Group G5 was treated topically with test item D and E, in combination, at the concentration of ⁇ g and 100 ⁇ g respectively.
  • Group G6 was treated orally with test item D at lmg/kg. After 30 min. of D administration, test item E was dosed orally at lOOmg/kg.
  • Group G7 served as both TPA control (right ear) and solvent control (left ear) and was treated orally with Na-CMC.
  • TPA solution containing 2 ⁇ g of TPA in vehicle 2% DMSO and 98% methanol
  • vehicle 2% DMSO and 98% methanol
  • the left ear of Group G7 animals was treated topically with 20 ⁇ , of solvent (2% Dimethylsulfoxide+98% methanol) on day 0, 2, 4, 7 and 9.
  • All the test item formulations was administered orally to Groups-G3, G4, and G6 at the dose volume of lOml/kg from day 0 to day 9.
  • 20 ⁇ of test items (3HX and D+E) was dissolved appropriately in the TPA solvent i.e. methanol and applied daily from Day 0 to Day 9 to Groups-Gl, G2 and G5.
  • the ear thickness was measured daily using digital caliper. On Day 10, animal's blood was withdrawn by retro-orbital plexus. Blood serum was separated for the estimation of nitric oxide level by Griess method. Further, all the animals were humanely sacrificed and ear punch biopsies were collected, weighed and subjected for histopatho logical analysis, immunohistochemical Ki- 67 staining and Myeloperoxidase (MPO) activity.
  • MPO Myeloperoxidase
  • Body weight of all the animals was recorded from day 0 to day 10.
  • the % change in body weight for each animal was calculated using the given formula:
  • Body Weight Change Body Weight at 'X' day-Body weight at day '0' X100
  • EAR THICKNESS CHANGE Mean ear thickness change or ear edema was calculated based on the absolute ear thickness values.
  • Ear thickness change (mm) (x) ⁇ Absolute ear thickness (mm) at "x" Time Point ⁇ - ⁇ Absolute ear thickness (mm) at day 0 ⁇
  • Photographs of ear was taken for each animal and presented.
  • Mean ear biopsy weight (4mm punch biopsy) was calculated and represented in tabulated and graphical form.
  • % Inhibition was tabulated and represented in graphical form.
  • MPO activity was performed by colorimetric method as described by Rajp et al. (2007).
  • IU/mL ⁇ X final volume in cuvette/8.3 X volume of sample added ( ⁇ ) X dilution factor. Where ⁇ is the average of change in absorbance per minute.
  • IU/gm tissue (IU/mL) / (gm tissue/mL)
  • Nitric oxide levels was also measured by colorimetric assay using Griess reagent. Briefly, equal volume of serum was mixed with Griess reagent and incubated for 15min at 37°C. Absorbance was measured at 546nm and percentage inhibition of nitric oxide level was calculated using the formula:
  • % Inhibition was tabulated and represented in graphical form.
  • MYELOPEROXIDASE (MPO) ACTIVITY was done by Two way and One way ANOVA followed by Posthoc-Bonferroni and Dunnet's test respectively, as it was appropriate for study data analysis.
  • Figure 33 illustrates effects of 3-HX and D & E treatment on Body weight change.
  • Figure 34 illustrates effects of 3-HX and D & E treatment on % Body Weight Change.
  • Figure 35 illustrates effects of topical application of 3-HX and D & E on Absolute Ear
  • Thickness in TPA induced mouse Thickness in TPA induced mouse.
  • Figure 36 illustrates effects of oral application of 3-HX and D & E on Absolute Ear Thickness in TPA induced mouse. EFFECT OF TREATMENT ON EAR THICKNESS CHANGE
  • Figure 38 illustrates effects of oral application of 3-HX and D & E on Ear Thickness Change (Effect of 3-HX and D & E oral treatment on thickness change in TPA induced mouse ear).
  • Figure 39 illustrates effects of 3-HX and D & E treatment on Ear Punch Biopsy Weight (mg).
  • Figures 40A-40G illustrates Photographs of ear, including:
  • Group 7 TP A Control (Right Ear) & Vehicle Control (Left Ear): G7A1-G7A6
  • G denotes Group Number and A denotes Animal number
  • Figure 41 depicts the % inhibition of ear inflammation on topical application of 3-HX and D & E.
  • 3-HX at the ratio of 1 :4 exerted 35.96% activity on Day 8 which sustained up to Day 9.
  • 3-HX at the ratio of 1 :8 exerted maximum inhibition activity of 52.44% on Day 9 treatment.
  • topical application of D & E exerted 64.94% inhibitory activity from Day 7 which sustained up to Day 9 treatment.
  • Figure 42 depicted the % inhibition of ear inflammation on oral administration of 3-HX and D & E.
  • 3-HX at both the doses of 500mg/kg and lOOOmg/kg exhibited approximately 32% inhibitory activity on Day 5 which subsequently got decreased on further treatment up to Day 9.
  • D & E oral administration exerted marginal inhibitory activity against TPA induced inflammation.
  • Table 8 % Inhibitory Activity of Ear Inflammation
  • Figure 41 shows % Inhibition of Ear Inflammation on topical treatment (% Inhibitory activity of 3-HX and D & E on topical application).
  • Figure 42 shows % Inhibition of Ear Inflammation on oral treatment (% Inhibitory activity of 3-HX and D & E on oral application).
  • the H&E-stained ear sections of all the experimental groups are represented in Figure 43. Edema and inflammatory cell infiltration are scored as nil (-), mild (+), moderate (++) and severe (+++). Moreover, the epidermal thickness was also calculated for all the experimental groups.
  • TPA application resulted in a marked increase in ear thickness with almost nil hyperkeratosis and moderate edema. Moreover, severe inflammatory cell infiltration in the dermis was also observed. A significant increase in epidermal ear thickness (P ⁇ 0.01) was also observed in TPA control group when compared with vehicle control (Table 9).
  • Topical administration of 3-HX at the ratio of 1 :4 showed almost nil hyperkeratosis and moderate edema. However, severe inflammatory cell infiltration was observed upon 10 days topical application. Similarly, topical administration of 3-HX at the ratio of 1 :8 showed mild hyperkeratosis and edema with severe inflammatory cell infiltration. D & E topical application for 10 consecutive days resulted into moderate hyperkeratosis with moderate edema and infiltration of inflammatory cells. The epidermal thickness was also observed to be significantly reduced on 3-HX topical treatment at both the ratios when compared with TPA control (P ⁇ 0.05). However, on D & E topical application no significant results were obtained when compared with TPA control (Figure 34).
  • 3-HX at the low dose of 500mg/kg resulted into mild hyperkeratosis and edema with moderate to severe infiltration of inflammatory cells.
  • 3-HX at the high dose of lOOOmg/kg resulted into mild to moderate hyperkeratosis and edema with severe infiltration of inflammatory cells.
  • oral administration of D & E leads to mild hyperkeratosis with moderate edema and severe inflammatory cell infiltration.
  • the epidermal ear thickness was also found to be significantly reduced on 3-HX treatment at higher dose of lOOOmg/kg alone (P ⁇ 0.05) ( Figure 35). However, in other oral treatment groups no significant differences were obtained in comparison with TPA control.
  • FIGURES 43A-43H HISTOPATHOLOGICAL FINDINGS
  • Group 2 3-HX (1 :8); Topical. Photographs of H&E-stained mouse ear cross-sections of 3-HX (1 :8; topical) treated mice in the TPA inflammation model. Reduction in hyperkeratosis and edema was observed (10X magnification).
  • Group 3 3-HX (500mg/kg); Oral. Photographs of H&E-stained mouse ear cross-sections of 3- HX (500mg/kg; oral) treated mice in the TPA inflammation model. Reduction in hyperkeratosis and edema was observed (10X magnification).
  • Group 4 3-HX (lOOOmg/kg); Oral. Photographs of H&E-stained mouse ear cross-sections of 3-HX (lOOOmg/kg; oral) treated mice in the TPA inflammation model. Reduction in hyperkeratosis and edema was observed (10X magnification).
  • Group 5 D & E; Topical. Photographs of H&E-stained mouse ear cross-sections of D & E topically treated mice in the TPA inflammation model. Reduction in hyperkeratosis, edema and inflammatory cell infiltration was observed (10X magnification).
  • Group 6 D & E; Oral. Photographs of H&E-stained mouse ear cross-sections of D & E orally treated mice in the TPA inflammation model. Reduction in hyperkeratosis and edema was observed (1 OX magnification) .
  • Group 7 TPA Control (Right Ear). Photographs of H&E-stained mouse ear cross-sections in the TPA induced inflammation model. Severe infiltration of inflammatory cells with moderate edema in ears was observed (10X magnification).
  • Group 7 Vehicle control (Left Ear). Photographs of H&E-stained mouse ear cross-sections of vehicle control group (10X magnification).
  • Figure 44 illustrates effects of topical application of 3-HX and D & E on epidermal ear thickness.
  • Figure 45 illustrates effects of oral treatment of 3-HX and D&E on epidermal ear thickness.
  • MPO MYELOPEROXIDASE
  • Table 10 illustrated the effect of test items over enzyme myeloperoxidase, released by neutrophils and macrophages during inflammation process.
  • the enzyme activity was found to be markedly enhanced in TPA control group when compared with vehicle control.
  • Topical application of 3-HX at both the ratios profoundly inhibited the MPO activity on 10 days of consecutive application in comparison with TPA control.
  • Topical application of standard D & E showed maximum inhibition of MPO activity among all the topical treatment groups (Figure 46).
  • Table 10 Effect of Test items Treatment on MPO activity in TPA induced mice ear
  • Figure46 illustrates effects of topical application of 3-HX and D & E on MPO activity in TPA induced mice ear.
  • Figure 47 illustrates effects of oral administration of 3-HX and D&E on MPO activity in TPA induced mice ear.
  • Table 11 illustrated the % inhibition of nitric oxide levels in serum of TPA induced
  • Topical application of 3-HX at both the ratios exerted poor inhibitory effect over nitric oxide levels on 10 days of consecutive application.
  • topical application of standard D & E also exhibited poor inhibitory response over serum NO levels.
  • Table 11 Effect of Test items Treatment on % Inhibition of Nitric oxide level in serum of TPA induced inflammation
  • n plasma samples size analyzed for NO activity
  • Figure 48 shows % Inhibition of serum Nitric oxide content on 3-HX and D&E treatment (Effect of 3-HX and D&E on serum nitric oxide level).
  • test items were further evaluated by measuring the standard 4mm punch biopsy weight after completion of treatment schedule. 10 consecutive day TPA application resulted in profound increase in punch biopsy weight of mice ear suggesting the chronic inflammatory response.
  • Topical application of D & E exerted maximum reduction in ear punch biopsy weight followed by 3- HX (1 :4) and 3-HX (1 :8).
  • Oral administration of 3-HX and D & E resulted in marginal reduction in ear punch biopsy weight suggesting the beneficial effect of test items on topical application in comparison with oral treatment.
  • the epidermal ear thickness was evaluated in histopatho logical photographs.
  • the histopathogical findings were in accordance with punch biopsy weight results where topical application of test items was found to exert better effect against TPA induced increase in epidermal ear thickness ear in comparison with orally treated experimental groups.
  • marked reduction in hyperkeratosis, ear edema and inflammatory cell infiltration was also observed among all the treatment groups when compared with TPA control.
  • Figure 49 illustrates the effect of proliferation of digoxin, Emodinemodin and their
  • Figure 50 illustrates the effect on live cells of three combinations of herbs each in three concentrations 1 :40, 1 :20 and 1 : 10.
  • CI includes Sheng Di Huang
  • C2 includes Jin Yin Hua, Da Huang, Mu Dan Pi and Di Gu Pi
  • C3 includes Xian He Cao and Chun Gen Pi.
  • Figure 50 illustrates that each of these three example combinations provides a reduction of the live cell numbers particularly in higher concentrations, while CI and C2 appear to be more effective than C3.
  • Each of CI and C2 includes one or two of the three herbs Sheng Di Huang, Jin Yin Hua and Da Huang, while C3 does not.
  • the combination of four herbs in C2 appears to be more effective than the single herb in CI .
  • Figures 51-53 illustrate plots for each of the eighteen herbs of growth as a percentage of control versus dilution factor.
  • Figures 51-53 illustrate that the three herbs Sheng Di Huang, Da Huang and Jin Yin Hua are most effective, while the four herbs Mu Dan Pi, Di Gu Pi, Xian He Cao and Chun Gen Pi are effective, and the eleven herbs Zi Cao, Xuan Shen, Shi Gao, Bai Shao, Chi Shao, Hong Hua, Da Qing Ye, Qing Dai, Bai Zhu, Shi Wei and Rou Gui are somewhat less effective.
  • Figure 54 illustrates the effect on live cells of five combinations of herbs each in two concentrations 1 :40 and 1 :80.
  • Cal includes a combination of all eighteen herbs
  • C2 includes a combination of Jin Yin Hua, Da Huang, Mu Dan Pi and Di Gu Pi
  • C3 includes a combination of Da Huang, Sheng Di Huang and Jin Yin Hua
  • C4 and C5 include combinations of the other eleven herbs (Zi Cao, Xuan Shen, Shi Gao, Bai Shao, Chi Shao, Hong Hua, Da Qing Ye, Qing Dai, Bai Zhu, Shi Wei and Rou Gui) of the eighteen herbs, i.e., not in combination with any of the seven herbs (Sheng Di Huang, Da Huang, Jin Yin Hua, Mu Dan Pi, Di Gu Pi, Xian He Cao and Chun Gen Pi).
  • C4 includes Shi Gao, Shi Wei, Bai Zhu, Rou Gui, Hong Hua and C5 includes Zi Cao, Xuan Shen, Chi Shao, Bai Shao, Da Qin Ye, and Qing Dai.
  • Figure 54 illustrates that combinations of all eighteen herbs, as well as combinations of the three herbs (Sheng Di Huang, Da Huang and Jin Yin Hua) are most effective, while the combination C2 was less effective, and the combinations C4 and C5 were still less effective.
  • the newly separated compounds may be each individually or in combination used as an ingredient to prepare a
  • compositions or formulations can be prepared from the substantially pure compound using conventional processes or future developed processes in the industry.
  • Specific processes of making pharmaceutical formulations and dosage forms (including, but not limited to, tablet, capsule, injection, syrup) from chemical compounds are not part of the invention and people of ordinary skill in the art of the pharmaceutical industry are capable of applying one or more processes established in the industry to the practice of the present invention.
  • people of ordinary skill in the art may modify the existing conventional processes to better suit the compounds of the present invention.
  • the patent or patent application databases provided at USPTO official website contain rich resources concerning making pharmaceutical formulations and products from effective chemical compounds.
  • Another useful source of information is Handbook of Pharmaceutical Manufacturing Formulations, edited by Sarfaraz K. Niazi and sold by Culinary & Hospitality Industry Publications Services, which is incorporated by reference.

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Abstract

La présente invention concerne un régime de traitement pour le psoriasis, l'eczéma ou une autre affection cutanée, une inflammation,une maladie auto-immune, la leucémie, le mélanome ou un autre cancer, consistant à administrer à un patient un régime de méthotrexate avec des doses périodiques d'une combinaison à base d'herbes médicinales comprenant Sheng Di Huang, Da Huang ou Jin Yin Hua ou des combinaisons de celles-ci.
PCT/US2015/038341 2015-06-29 2015-06-29 Combinaisons moléculaires et à base d'herbes médicinales avec du méthotrexate pour le traitement de maladies et d'affections inflammatoires WO2017003430A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070166362A1 (en) * 2004-10-07 2007-07-19 Shuji Sakuma Transdermal and transmucosal preparations
US20130045179A1 (en) * 2011-08-15 2013-02-21 Mihai Ciustea Combination therapy and methods for treatment and prevention of hyperproliferative diseases
US20140205685A1 (en) * 2010-11-13 2014-07-24 Sirbal, Ltd. Herbal Combinations for Treatment of a Skin Condition

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070166362A1 (en) * 2004-10-07 2007-07-19 Shuji Sakuma Transdermal and transmucosal preparations
US20140205685A1 (en) * 2010-11-13 2014-07-24 Sirbal, Ltd. Herbal Combinations for Treatment of a Skin Condition
US20130045179A1 (en) * 2011-08-15 2013-02-21 Mihai Ciustea Combination therapy and methods for treatment and prevention of hyperproliferative diseases

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