CN114042068A - Medicine prepared from neferine, capsaicin and 6-gingerol for inhibiting benign prostatic hyperplasia and application thereof - Google Patents

Medicine prepared from neferine, capsaicin and 6-gingerol for inhibiting benign prostatic hyperplasia and application thereof Download PDF

Info

Publication number
CN114042068A
CN114042068A CN202111470728.7A CN202111470728A CN114042068A CN 114042068 A CN114042068 A CN 114042068A CN 202111470728 A CN202111470728 A CN 202111470728A CN 114042068 A CN114042068 A CN 114042068A
Authority
CN
China
Prior art keywords
neferine
gingerol
capsaicin
prostatic hyperplasia
benign prostatic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202111470728.7A
Other languages
Chinese (zh)
Inventor
刘棋铭
邵子辰
吴正平
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Yichun University
Original Assignee
Yichun University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yichun University filed Critical Yichun University
Priority to CN202111470728.7A priority Critical patent/CN114042068A/en
Publication of CN114042068A publication Critical patent/CN114042068A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A61K31/12—Ketones
    • 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
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Polymers & Plastics (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Mycology (AREA)
  • Botany (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to a benign prostatic hyperplasia inhibiting medicine prepared from neferine, capsaicin and 6-gingerol and application thereof. The medicine for inhibiting benign prostatic hyperplasia comprises one or more of capsaicin, neferine and 6-gingerol. The capsaicin can inhibit the growth of prostate epithelial cells, various cancer cells have an anti-proliferation effect, the neferine can be used as 5 alpha-reductase for inhibiting and further resisting prostatic hyperplasia/hypertrophy, and the 6-gingerol is one of active ingredients extracted from ginger and has the pharmacological effects of resisting oxidation, reducing blood fat, diminishing inflammation and resisting proliferation.

Description

Medicine prepared from neferine, capsaicin and 6-gingerol for inhibiting benign prostatic hyperplasia and application thereof
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a benign prostatic hyperplasia inhibiting medicine prepared from neferine, capsaicin and 6-gingerol and application thereof.
Background
Benign prostatic hyperplasia is a common urinary tract disorder in men and is characterized by hyperplasia of the prostate gland and smooth muscle. Resulting in urethral compression of patients, urinary retention and urethral infection. The disease is better for middle-aged men over 50 years old, and the incidence rate of the disease is increased year by year with the increase of the elderly population. Causing benign prostatic hyperplasia is associated with an androgen imbalance, which causes prostatic hyperplasia through androgen receptors and interfering signaling pathways.
Clinically, surgery and medicine are adopted to treat symptoms caused by prostatic hyperplasia. The aim of drug therapy is to specifically relax prostate smooth muscle and reduce prostate volume. Alpha receptor blockers cause contraction of prostate smooth muscle by blocking sympathetic nerve excitation, reducing micturition disorders, but are prone to hypotensive side effects. Blocking the conversion of androgens to dihydroandrogens by 5 alpha reductase inhibitors reduces prostate volume hyperplasia.
In modern pharmacological research, the traditional Chinese medicine prescription medicine for prostate mainly utilizes active ingredients of medicinal materials. The traditional Chinese medicine composition inhibits the hyperplasia of prostate cells through interfering a signal path. However, there are fewer studies in this area and fewer therapeutic drugs are being developed. Therefore, the invention provides a new treatment scheme for reducing the side effect of the existing oral medicines for treating the benign prostatic hyperplasia and reducing the urination disorder caused by the benign prostatic hyperplasia. Especially aims at improving symptoms such as androgen level imbalance and the like existing in a patient with chronic prostatic hyperplasia, thereby improving the life quality of the patient.
Disclosure of Invention
In order to solve the technical problems, the invention provides a benign prostatic hyperplasia inhibiting medicine prepared from neferine, capsaicin and 6-gingerol and application thereof.
The invention aims to provide a benign prostatic hyperplasia inhibiting medicine prepared from capsaicin, neferine and 6-gingerol, wherein the benign prostatic hyperplasia inhibiting medicine comprises one or more of the combination of the capsaicin, the neferine and the 6-gingerol.
Preferably, in the above drugs, when the benign prostatic hyperplasia treatment drug is a combination of capsaicin and neferine and acts on cells, the molar ratio of the capsaicin to the neferine is 1: 1-10; preferably, the molar ratio of the capsaicin to the neferine is 1: 10;
when the benign prostatic hyperplasia treatment drug is a combination of capsaicin and neferine and acts on animals, the mass ratio of the capsaicin to the neferine is 5: 1.
When the benign prostatic hyperplasia treatment drug is a combination of 6-gingerol and neferine and acts on cells, the molar ratio of 6-gingerol to neferine is 1: 1-10; preferably, the molar ratio of the 6-gingerol to the neferine is 1: 10;
when the benign prostatic hyperplasia treatment drug is a combination of 6-gingerol and neferine and acts on animals, the mass ratio of 6-gingerol to neferine is 5: 1.
The invention also provides the application of capsaicin, neferine and 6-gingerol in preparing the benign prostatic hyperplasia inhibiting medicine.
Preferably, in the above uses, the medicament for inhibiting benign prostatic hyperplasia is used for preparing the inhibitor for human prostatic epithelial cells and human normal prostatic stromal cells.
Preferably, in the above application, the benign prostatic hyperplasia inhibiting drug is prepared into a pharmaceutically acceptable dosage form, and the dosage form is tablets, granules, powder, oral liquid or capsules.
Preferably, in the above use, the concentration of each of capsaicin, neferine and 6-gingerol in the drug for inhibiting benign prostatic hyperplasia is 10 to 100 μ M.
Preferably, in the above use, when capsaicin and neferine are combined, the concentrations of capsaicin and neferine are 10 μ M and 100 μ M, respectively, or 10 μ M and 10 μ M, respectively.
Preferably, in the above application, when the 6-gingerol and the neferine are combined, the concentrations of the 6-gingerol and the neferine are respectively 10 μ M and 100 μ M, or respectively 10 μ M and 10 μ M.
Preferably, in the above use, the benign prostatic hyperplasia-inhibiting drug is used for preparing an anti-proliferative drug for benign prostate in a male human or a male mammal.
Preferably, in the above use, the male mammal is a mouse, and the amounts of capsaicin, neferine and 6-gingerol used in the mouse are 10mg/kg, 2mg/kg and 10mg/kg, respectively.
Compared with the prior art, the invention has the following beneficial effects:
the invention treats prostate diseases by inhibiting prostate hyperplasia, resisting inflammation and improving local microcirculation. The capsaicin is one of the active ingredients of the capsicum, and has the pharmacological effects of relieving pain, relieving itching, resisting oxidation, resisting cancer, resisting hyperplasia, resisting inflammation, resisting lipid peroxidation, and the like; the research of the invention shows that the capsaicin with the concentration of 100 mu M can inhibit the growth of prostate epithelial cells by 46 percent at 48, and the capsaicin also has the anti-hyperplasia effect on various cancer cells.
The plumula Nelumbinis is green embryo of mature seed of Nelumbo nucifera Gaertn of Nymphaeaceae, and its extract contains liensinine, isoliensinine, neferine, nuciferine, hyperin, rutin, etc. The neferine is one of active ingredients extracted from green plumula Nelumbinis of mature seed of Nelumbo nucifera Gaertn of Nelumbonaceae, and has antiarrhythmic, blood pressure lowering, platelet aggregation inhibiting, antioxidant, anti-inflammatory, and antiproliferative physiological effects; the research of the invention shows that neferine can be used as 5 alpha-reductase for inhibiting, and further resisting prostatic hyperplasia/hypertrophy.
The rhizoma Zingiberis recens extract is fresh rhizome extract of rhizoma Zingiberis recens of Zingiber of Zingiberaceae, and contains gingerol, shogaol, bisabolene, gingerol, etc. The 6-gingerol is one of active ingredients extracted from rhizoma Zingiberis recens, and has antioxidant, blood lipid reducing, antiinflammatory, and antiproliferative physiological effects.
In the invention, neferine, capsaicin and 6-gingerol are used as 5 alpha-reductase inhibitors and as drugs for inhibiting cell proliferation, and the neferine, the capsaicin and the 6-gingerol can be used as drugs, health-care food or food additives for relieving symptoms of prostatic hyperplasia/hypertrophy.
Drawings
FIG. 1 shows the expression of 5. alpha. -reductase, PSA protein, in human prostate epithelial cells of the present invention, after 24 hours of exposure to various concentrations of compounds.
Detailed Description
In order that those skilled in the art will better understand the technical solutions of the present invention to be implemented, the present invention will be further described with reference to the following specific embodiments and accompanying drawings.
Experimental example 1 anti-prostate cell proliferation
The purpose of this experimental example is to verify that capsaicin 10. mu.M and 100. mu.M, neferine 10. mu.M and 100. mu.M, and 6-gingerol 10. mu.M and 100. mu.M have the effect of resisting prostate cell proliferation by cell experiments. All drugs were dissolved in dimethyl sulfoxide solution, which was less than 0.1%, v/v, and added to the medium. Culturing human prostate epithelial cell strain LNCaP and human normal prostate stromal cell WPMY-1 in 96-well plate with appropriate cell culture solution at 37 deg.C with 5% CO2Incubating for about 48h under the condition, and adding the medicine after the cells are attached and grow on the culture disc. LNCaP cells were incubated in RPMI-1640 medium and WPMY-1 cells were incubated in DMEM medium.
Drug addition experiments were divided into 9 groups: (1) a control group, containing only culture medium and corresponding cells, without any drug addition; (2) capsaicin, which is calculated by the volume of a culture medium, and is respectively provided with two final concentration drug experiments of 10 mu M and 100 mu M; (3) the neferine group is respectively provided with two final concentration drug experiments of 10 mu M and 100 mu M based on the volume of the culture medium; (4) 6-gingerol group, which is calculated by the volume of the culture medium, and is respectively provided with two final concentration drug experiments of 10 mu M and 100 mu M; (5) the final concentrations of the high-concentration neferine and the capsaicin combined group are respectively set to be 100 mu M and 10 mu M based on the volume of the culture medium; (6) the final concentrations of the low-concentration neferine and capsaicin combined group are respectively set to be 10 mu M and 10 mu M in terms of the volume of the culture medium; (7) the high-concentration neferine is combined with the 6-gingerol group, and the final concentrations of the high-concentration neferine and the 6-gingerol group are respectively set to be 100 mu M and 10 mu M in terms of the volume of the culture medium; (8) the low-concentration neferine is combined with the 6-gingerol group, and the final concentrations of the two groups are respectively set to be 10 mu M and 10 mu M according to the volume of the culture medium; (9) the positive control group finasteride (Shanghai Aladdin Biotechnology Co., Ltd.) was prepared by 10. mu.M and 100. mu.M of the culture medium by volume. When the drug is added, the drug is prepared into stock solution with the concentration more than 1000 times of the final concentration, then the addition amount of the stock solution is calculated according to the final concentration, and the stock solution is added into the culture medium, so that the phenomenon of killing cells by a solvent is avoided.
After 48h incubation, washed with PBS (pH7.4, potassium dihydrogen phosphate 2mM, disodium hydrogen phosphate 8mM, sodium chloride 136mM, potassium chloride 2.6mM) and replaced with fresh medium, 10. mu. LMTT (5mg/ml) was added to each well, and 5% CO was added at 37 ℃ to the wells2After incubation for 4h in a cell incubator, the liquid in the wells was removed and 100. mu.L of dimethyl sulfoxide was added to dissolve the purple crystals. And uniformly mixing the liquid in each hole, taking out the sample, placing the sample at room temperature for 20min, measuring the absorbance at 570nm, and calculating the cell activity.
Cell activity ═ (absorbance of experimental group-absorbance of control group)/(absorbance of control group) × 100%.
The results of the cell activity calculation are shown in table 1, the experimental data in table 1 are expressed by mean ± standard deviation, the statistical analysis of the experimental results is performed, and the difference with P <0.05 is statistically significant. The results in Table 1 demonstrate that capsaicin, neferine, 6-gingerol and combinations thereof all have significant antiproliferative effects on prostate epithelial cell glandular stromal cells.
TABLE 1 measurement of cell Activity
Figure BDA0003391960680000051
Note: denotes P <0.05 compared to control group.
Experimental example 2 antiandrogen-induced prostate cell proliferation
The purpose of this experimental example is to verify that capsaicin 10. mu.M and 100. mu.M, neferine 10. mu.M and 100. mu.M, and 6-gingerol 10. mu.M and 100. mu.M have the effect of resisting prostate cell proliferation by cell experiments. All the medicines are dissolved by dimethyl sulfoxide solution and then added into a culture medium,the concentration of the dimethyl sulfoxide solution is less than 0.1 percent, v/v. Culturing human prostate epithelial cell strain LNCaP and human normal prostate stromal cell WPMY-1 in 96-well plate with appropriate cell culture solution at 37 deg.C with 5% CO2Incubating for about 48h under the condition, and adding the medicine after the cells are attached and grow on the culture disc. LNCaP cells were incubated in RPMI-1640 medium and WPMY-1 cells were incubated in DMEM medium. When the drug is added, the drug is prepared into stock solution with the concentration more than 1000 times of the final concentration, then the addition amount of the stock solution is calculated according to the final concentration, and the stock solution is added into the culture medium, so that the phenomenon of killing cells by a solvent is avoided.
Drug addition experiments were divided into 14 groups: (1) a control group, containing only culture medium and corresponding cells, without any drug addition; (2) testosterone group, the final concentration of the drug is set to be 1 mu M based on the volume of the culture medium; (3) the final concentration of the drug is respectively set to be 1 mu M and 10 mu M by the volume of the culture medium in the testosterone combined low-concentration capsaicin group; (4) the final concentration of the drug is respectively 1 mu M and 100 mu M based on the volume of the culture medium by combining testosterone with high-concentration capsaicin; (5) the final concentrations of the testosterone group and the low-concentration neferine group are respectively set to be 1 mu M and 10 mu M based on the volume of the culture medium; (6) the final concentrations of the testosterone group and the high-concentration neferine group are respectively set to be 1 mu M and 100 mu M based on the volume of the culture medium; (7) testosterone is combined with a low-concentration 6-gingerol group, and the final concentrations of the drugs are respectively set to be 1 mu M and 10 mu M based on the volume of a culture medium; (8) the final concentration of the drug is respectively set to be 1 mu M and 100 mu M by the volume of the culture medium by combining the testosterone with the high-concentration 6-gingerol group; (9) the final concentrations of the combination of testosterone and high-concentration neferine and capsaicin are respectively set to be 1 mu M, 100 mu M and 10 mu M based on the volume of a culture medium; (10) the final concentrations of the drug in the testosterone group combined with the low-concentration neferine and the capsaicin group are respectively set to be 1 mu M, 10 mu M and 10 mu M based on the volume of the culture medium; (11) testosterone is combined with high-concentration neferine and 6-gingerol, and the final concentrations of the medicaments are respectively set to be 1 mu M, 100 mu M and 10 mu M in terms of the volume of a culture medium; (12) the final concentrations of the testosterone, the low-concentration neferine and the 6-gingerol group are respectively set to be 1 mu M, 10 mu M and 10 mu M according to the volume of a culture medium; (13) positive control group: the combination of testosterone and low-concentration finasteride (Shanghai Aladdin Biotechnology Co., Ltd.) comprises 1 μ M and 10 μ M of the medicine respectively based on the volume of the culture medium; (14) positive control group: the combination of testosterone and finasteride (Shanghai Aladdin Biotechnology Co., Ltd.) with high concentration is set to 1 μ M and 100 μ M respectively based on the volume of the culture medium. When the drug is added, the drug is prepared into a stock solution with a concentration more than 1000 times of the final concentration, and then the stock solution is added into the culture medium, so that the phenomenon of killing cells by a solvent is avoided.
After 48h incubation, washed with PBS (pH7.4, potassium dihydrogen phosphate 2mM, disodium hydrogen phosphate 8mM, sodium chloride 136mM, potassium chloride 2.6mM) and replaced with fresh medium, 10. mu. LMTT (5mg/ml) was added to each well, and 5% CO was added at 37 ℃ to the wells2After incubation for 4h in a cell incubator, the liquid in the wells was removed and 100. mu.L of dimethyl sulfoxide was added to dissolve the purple crystals. And uniformly mixing the liquid in each hole, taking out the sample, placing the sample at room temperature for 20min, measuring the absorbance at 570nm, and calculating the cell activity.
Cell activity ═ (absorbance of experimental group-absorbance of control group)/(absorbance of control group) × 100%.
The results of the cell activity calculations are shown in table 2, where the experimental data in table 2 are expressed as mean ± standard deviation, and the experimental results are statistically analyzed, and the difference with P <0.05 is statistically significant. The results in Table 2 demonstrate that capsaicin, neferine, 6-gingerol and combinations thereof all have significant antiproliferative effects on prostate epithelial cell glandular stromal cells.
TABLE 2 measurement of cell Activity
Figure BDA0003391960680000071
Note: denotes P <0.05 compared to control group. # denotes P <0.05 compared to testosterone.
Experimental example 3 anti-androgen induces expression of 5 alpha-reductase and PSA protein in prostate epithelial cells
In benign prostatic hyperplasia, testosterone is converted into dihydrotestosterone by 5 alpha-reductase, and if the expression of the 5 alpha-reductase is effectively reduced, prostatic cell hyperplasia can be inhibited. Capsaicin (10 mu M and 100 mu M), neferine (10 mu M and 100 mu M), 6-gingerol (10 mu M and 100 mu M) and neferine (100 mu M) are respectively combined with 6-gingerol (100 mu M) and capsaicin (100 mu M) to act on LNCaP cells according to the experimental method of example 1, cell proteins are extracted after 24 hours, the expression levels of 5 alpha-reductase and PSA protein in the cells are detected, and the effect of the compound on inhibiting the androgen-induced prostate cell proliferation by regulating the expression of the two proteins is evaluated.
FIG. 1 is a graph showing the protein level expression of 5. alpha. -reductase and PSA proteins in prostate epithelial cells after they have been exposed to different concentrations of the compound for 24 hours. Beta-actin is an internal reference. The results in FIG. 1 show that neferine (10, 100. mu.M), 6-gingerol (10, 100. mu.M), and capsaicin (10, 100. mu.M) have the effect of inhibiting prostate 5. alpha. -reductase, thereby reducing PSA expression, exhibiting an antiproliferative effect.
Example 4 animal experiments with benign prostatic hyperplasia
Animal and reagent preparation: in this example, 42 healthy male mice were purchased, aged about 6 to 7 weeks and weighed between 20 to 30g, and were kept for 1 week after purchase. The environment for raising male mice was set at 23 + -1 deg.C and 12h/12h day and night cycle, and these male mice were able to eat and drink water by themselves.
On the other hand, a finasteride reagent (Shanghai Aladdin Biotechnology Co., Ltd.) was prepared at a concentration of 10mg/kg, and a corn oil was used as a solvent for the preparation of the finasteride reagent. Corn oil is purchased from Xian Yuelai pharmaceutical science and technology Limited as a pharmaceutical adjuvant.
Grouping: the mice were randomly divided into 7 groups of 6 mice each, (1) vehicle group with 0.2mL corn oil as additive; (2) a model group, namely a model mouse constructed by the following method; (3) a capsaicin group, wherein the added medicine is 10mg/kg of capsaicin; (4) the neferine group is added with 2mg/kg neferine; (5) 6-gingerol group, the added medicine is 10mg/kg 6-gingerol; (6) compounding, wherein the added medicines comprise capsaicin 10mg/kg and neferine 2 mg/kg; or the combination of 2mg/kg of neferine and 10mg/kg of 6-gingerol; (7) in the positive control group, the added medicament is finasteride 10 mg/kg.
Note that "mg/kg" in the above group means the amount added per kg body weight of the mouse.
Experimental experiments: a mouse was obtained by intramuscular-injecting a testosterone propionate solution (Shanghai Alatin Biotechnology Co., Ltd.) at a concentration of 7.5mg/kg once a day, 150. mu.L of the testosterone propionate solution each time, and orally administering the resulting solution for two weeks using a feeder to thereby cause benign prostatic hyperplasia. After sacrifice, blood samples were taken from the heart. Before analyzing the sample, blood was centrifuged at 3000g for 10min after coagulation to obtain serum, which was stored at-20 ℃. Prostate specific antigen content in serum was determined using the prostate specific antigen kit (jingmei ELSIA kit). The mice take the prostate and clear the adjacent blood vessels and connective tissue. The sham operated control group was also removed from its prostate via the same manner as described above. The prostate index is calculated as the weight of the total weight of the prostate gland over the total body weight: prostate index (total prostate weight/total body weight) x 100%, results are shown in tables 3-4. From the data in tables 3 and 4, it is known that testosterone propionate promotes a significant increase in prostate wet weight, prostate index and PSA, which is evidence of prostate hyperplasia. The results show that the neferine, the 6-gingerol and the capsaicin have the effect of resisting prostatic hyperplasia by using the neferine (2mg/kg), the 6-gingerol (10mg/kg) and the capsaicin (10mg/kg) singly or in combination to effectively reduce and promote the wet weight of prostate, the prostate index and the PSA.
TABLE 3 Effect of neferine, 6-gingerol, capsaicin alone and in combination on mouse serum PSA
Group of PSA(ng/mL)
Vector set 1978.10±293.705#
Model group: testosterone propionate 7.5mg/kg 2642.42±107.14*
Neferine 2mg/kg 2332.88±38.01*#
Capsaicin 10mg/kg 2412.22±119.77*#
6-gingerol 10mg/kg 2318.27±268.58*#
2mg/kg of neferine and 10mg/kg of 6-gingerol 2059±123.66#
Neferine 2mg/kg + Capsici fructus 10mg/kg 1983.5±53.51#
Finasteride 10mg/kg 2342.99±219.98*#
Note: denotes P <0.05 compared to vehicle group and # denotes P <0.05 compared to model group.
TABLE 4 influence of neferine, 6-gingerol, capsaicin alone and in combination on prostate wet weight in mice
Figure BDA0003391960680000091
Figure BDA0003391960680000101
Note: denotes P <0.05 compared to vehicle group and # denotes P <0.05 compared to testosterone propionate group.
It should be noted that, when the present invention relates to a numerical range, it should be understood that two endpoints of each numerical range and any value between the two endpoints can be selected, and since the steps and methods adopted are the same as those in the embodiment, in order to prevent redundancy, the present invention describes a preferred embodiment. While preferred embodiments of the present invention have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts. Therefore, it is intended that the appended claims be interpreted as including preferred embodiments and all such alterations and modifications as fall within the scope of the invention.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.

Claims (10)

1. The medicine for inhibiting benign prostatic hyperplasia is prepared from capsaicin, neferine and 6-gingerol, and is characterized in that the medicine for inhibiting benign prostatic hyperplasia contains one or more of the combination of capsaicin, neferine and 6-gingerol.
2. The drug for inhibiting benign prostatic hyperplasia, which is prepared from capsaicin, neferine and 6-gingerol according to claim 1, wherein when the drug for treating benign prostatic hyperplasia is a combination of capsaicin and neferine and acts on cells, the molar ratio of the capsaicin to the neferine is 1: 1-10;
when the benign prostatic hyperplasia treatment drug is a combination of capsaicin and neferine and acts on an animal, the mass ratio of the capsaicin to the neferine is 5: 1;
when the benign prostatic hyperplasia treatment drug is a combination of 6-gingerol and neferine and acts on cells, the molar ratio of 6-gingerol to neferine is 1: 1-10;
when the benign prostatic hyperplasia treatment drug is a combination of 6-gingerol and neferine and acts on animals, the mass ratio of 6-gingerol to neferine is 5: 1.
3. Use of capsaicin, neferine, and 6-gingerol for the preparation of the medicament according to claim 1 for inhibiting benign prostatic hyperplasia.
4. Use according to claim 3, wherein the medicament for inhibiting benign prostatic hyperplasia is used for preparing an inhibitor of human prostate epithelial cells and human normal prostate stromal cells.
5. The use according to claim 1, wherein the benign prostatic hyperplasia inhibiting drug is formulated into a pharmaceutically acceptable dosage form, which is a tablet, granule, powder, oral liquid or capsule.
6. The use as claimed in claim 5, wherein the concentrations of capsaicin, neferine and 6-gingerol in the medicament for inhibiting benign prostatic hyperplasia are 10-100 μ M.
7. The use as claimed in claim 6, wherein the concentrations of capsaicin and neferine are 10 μ M and 100 μ M, respectively, or 10 μ M and 10 μ M, respectively, when the capsaicin and neferine are combined.
8. The use according to claim 6, wherein when 6-gingerol and neferine are combined, the concentrations of 6-gingerol and neferine are 10 μ M and 100 μ M, respectively, or 10 μ M and 10 μ M, respectively.
9. The use according to claim 5, wherein the benign prostatic hyperplasia-inhibiting medicament is used for preparing a benign prostatic anti-proliferative medicament for male humans or male mammals.
10. The use according to claim 9, wherein the male mammal is a mouse, and the amounts of capsaicin, neferine, and 6-gingerol used in the mouse are 10mg/kg, 2mg/kg, and 10mg/kg of body weight, respectively.
CN202111470728.7A 2021-12-03 2021-12-03 Medicine prepared from neferine, capsaicin and 6-gingerol for inhibiting benign prostatic hyperplasia and application thereof Pending CN114042068A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111470728.7A CN114042068A (en) 2021-12-03 2021-12-03 Medicine prepared from neferine, capsaicin and 6-gingerol for inhibiting benign prostatic hyperplasia and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111470728.7A CN114042068A (en) 2021-12-03 2021-12-03 Medicine prepared from neferine, capsaicin and 6-gingerol for inhibiting benign prostatic hyperplasia and application thereof

Publications (1)

Publication Number Publication Date
CN114042068A true CN114042068A (en) 2022-02-15

Family

ID=80212426

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111470728.7A Pending CN114042068A (en) 2021-12-03 2021-12-03 Medicine prepared from neferine, capsaicin and 6-gingerol for inhibiting benign prostatic hyperplasia and application thereof

Country Status (1)

Country Link
CN (1) CN114042068A (en)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001288077A (en) * 2000-04-07 2001-10-16 Shokun An Therapeutic agent for chronic prostatitis, prostatomegaly, hemorrhoids and erection failure utilizing capsaicin
CN101862312A (en) * 2009-04-14 2010-10-20 中国中医科学院中药研究所 New application of 6-gingerol
CN101862374A (en) * 2010-06-12 2010-10-20 李宏 Lotus plumule and new application of extractive thereof
CN101862331A (en) * 2009-04-14 2010-10-20 中国中医科学院中药研究所 New use of methyl liensinine
CN104856995A (en) * 2015-04-24 2015-08-26 西安交通大学 Application of lotus plumule active alkaloid in preparation of prostate drugs
CN113546065A (en) * 2021-09-07 2021-10-26 宜春学院 Application of 6-gingerol in preparing medicine for treating and preventing prostate cancer and resisting prostate cancer metastasis

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001288077A (en) * 2000-04-07 2001-10-16 Shokun An Therapeutic agent for chronic prostatitis, prostatomegaly, hemorrhoids and erection failure utilizing capsaicin
CN101862312A (en) * 2009-04-14 2010-10-20 中国中医科学院中药研究所 New application of 6-gingerol
CN101862331A (en) * 2009-04-14 2010-10-20 中国中医科学院中药研究所 New use of methyl liensinine
CN101862374A (en) * 2010-06-12 2010-10-20 李宏 Lotus plumule and new application of extractive thereof
CN104856995A (en) * 2015-04-24 2015-08-26 西安交通大学 Application of lotus plumule active alkaloid in preparation of prostate drugs
CN113546065A (en) * 2021-09-07 2021-10-26 宜春学院 Application of 6-gingerol in preparing medicine for treating and preventing prostate cancer and resisting prostate cancer metastasis

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
杨小青等: "甲基莲心碱和异莲心碱对5α-还原酶抑制作用的研究", 《中国药师》 *

Similar Documents

Publication Publication Date Title
Hu et al. Melatonin inhibits endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation in lipopolysaccharide-induced endometritis in mice
Yakubu et al. Antidiarrhoeal activity of aqueous extract of Mangifera indica L. leaves in female albino rats
Yan et al. Aqueous extracts of Herba Cistanche promoted intestinal motility in loperamide-induced constipation rats by ameliorating the interstitial cells of cajal
May et al. The effects of Momordica charantia (bitter melon) supplementation in patients with primary knee osteoarthritis: A single-blinded, randomized controlled trial
BR112016010509B1 (en) USES OF A SOLID ORAL DOSAGE FORM
KR20080015761A (en) Compositions for improving obesity
US11116781B2 (en) Composition, containing Loganin or a derivative thereof as an active ingredient for preventing, remedying, or treating female climacteric syndrome
TWI776234B (en) Pharmaceutical compositions and uses thereof in treating muscle atrophy
CN111265599A (en) Application of lycopene and grape seed composition in preparation of medicine for treating arthritis
CN101474271B (en) Medicament for treating uarthritis
Raghavendran et al. Ginsenoside rich fraction of Panax ginseng CA Meyer improve feeding behavior following radiation-induced pica in rats
CN114042068A (en) Medicine prepared from neferine, capsaicin and 6-gingerol for inhibiting benign prostatic hyperplasia and application thereof
KR20180117065A (en) Composition for preventing, improving or treating stress diseases comprising Platycodi Radix extract
CN110613712B (en) Chinese medicinal composition and its application in treating vasculitis and endothelial injury
CN1911260A (en) Application of phenolic acids active components from dandelion for inhibiting gynecologic pelvic inflammatory disease
CN111956751A (en) Pharmaceutical composition for treating hyperuricemia and preparation method thereof
US7556828B2 (en) Pharmaceutical composition for treatment of BPH and preparation thereof
US20040101584A1 (en) Control of cancer with annonaceous extracts
JP4706174B2 (en) α-Glucosidase inhibitor
JP2016531141A (en) Weight gain control using dibenzo-alpha-pyrone
Tope et al. Mechanisms of antiulcerogenic effect of garlic (Allium sativum) in albino rats
Lumlerdkij Thai traditional medicine as a source for cancer prevention: from local concepts to the discovery of potential chemopreventive extracts
KR20130046094A (en) Medical composition comprising abutilon avicennae extract for preventing or treating inflammatory disease
Rahman et al. Antidepressant-like effect of methanolic extract of Punica granatum (pomegranate) in mice model of depression
KR100773246B1 (en) Composition comprising of trillium kamtschaticum extracts as an effective ingredient for decreasing weight gain and lowering plasma glucose level

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination