CN106880627A - Osthole as the ERs activator of α 36 purposes - Google Patents
Osthole as the ERs activator of α 36 purposes Download PDFInfo
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- CN106880627A CN106880627A CN201510934203.2A CN201510934203A CN106880627A CN 106880627 A CN106880627 A CN 106880627A CN 201510934203 A CN201510934203 A CN 201510934203A CN 106880627 A CN106880627 A CN 106880627A
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- osthole
- ers
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- disease
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- HPUXDMUGCAWDFW-UHFFFAOYSA-N Osthole Natural products COc1ccc2CCC(=O)Oc2c1C=CC(=O)C HPUXDMUGCAWDFW-UHFFFAOYSA-N 0.000 title claims abstract description 43
- MBRLOUHOWLUMFF-UHFFFAOYSA-N osthole Chemical compound C1=CC(=O)OC2=C(CC=C(C)C)C(OC)=CC=C21 MBRLOUHOWLUMFF-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 239000012190 activator Substances 0.000 title claims abstract description 13
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 10
- 201000010099 disease Diseases 0.000 claims abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 6
- 235000013402 health food Nutrition 0.000 claims abstract description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 5
- 206010061218 Inflammation Diseases 0.000 claims abstract description 5
- 206010061246 Intervertebral disc degeneration Diseases 0.000 claims abstract description 5
- 208000037093 Menstruation Disturbances Diseases 0.000 claims abstract description 5
- 206010027339 Menstruation irregular Diseases 0.000 claims abstract description 5
- 206010039966 Senile dementia Diseases 0.000 claims abstract description 5
- 208000018180 degenerative disc disease Diseases 0.000 claims abstract description 5
- 230000036039 immunity Effects 0.000 claims abstract description 5
- 208000000509 infertility Diseases 0.000 claims abstract description 5
- 230000036512 infertility Effects 0.000 claims abstract description 5
- 231100000535 infertility Toxicity 0.000 claims abstract description 5
- 230000004054 inflammatory process Effects 0.000 claims abstract description 5
- 208000021600 intervertebral disc degenerative disease Diseases 0.000 claims abstract description 5
- 230000003349 osteoarthritic effect Effects 0.000 claims abstract description 5
- 239000004480 active ingredient Substances 0.000 claims abstract 2
- 230000000694 effects Effects 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- -1 pulvis Substances 0.000 claims description 4
- 239000002086 nanomaterial Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 230000007423 decrease Effects 0.000 claims 1
- 210000001672 ovary Anatomy 0.000 claims 1
- 208000002500 Primary Ovarian Insufficiency Diseases 0.000 abstract description 4
- 206010036601 premature menopause Diseases 0.000 abstract description 4
- 208000017942 premature ovarian failure 1 Diseases 0.000 abstract description 4
- 210000004027 cell Anatomy 0.000 description 14
- 210000002997 osteoclast Anatomy 0.000 description 11
- 230000027455 binding Effects 0.000 description 6
- 238000009739 binding Methods 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 229940011871 estrogen Drugs 0.000 description 5
- 239000000262 estrogen Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000009137 competitive binding Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 241000356446 Cnidium monnieri Species 0.000 description 3
- 235000019084 Selinum monnieri Nutrition 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000002860 competitive effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000005336 cracking Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
- 101710127797 Macrophage colony-stimulating factor 1 Proteins 0.000 description 1
- 102000014128 RANK Ligand Human genes 0.000 description 1
- 108010025832 RANK Ligand Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000007227 biological adhesion Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940126678 chinese medicines Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 201000003914 endometrial carcinoma Diseases 0.000 description 1
- 230000001076 estrogenic effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 210000000003 hoof Anatomy 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000001599 osteoclastic effect Effects 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
- A61K31/37—Coumarins, e.g. psoralen
-
- 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)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses Osthole as the ERs activator of α 36 purposes.Purposes of the Osthole as the ERs activator of α 36 in the medicine or health food for preparing anti-curing osteoporosis, premature ovarian failure, climacteric metancholia, irregular menstruation, infertility, degenerative disc disease, osteoarthritic inflammation and immunity disease, angiocardiopathy, senile dementia or bone metastaes.The invention also discloses a kind of ERs activator of α 36, its active ingredient is Osthole, and concentration is 0.01-10 μM.
Description
Technical field
The present invention relates to the new application of Osthole.
Background technology
ERs is expressed in various kinds of cell in vivo, is distributed in the tissues such as uterus, vagina, breast, pelvic cavity (ligament and knot hoof tissue) and skin, bladder, urethra, bone and brain.Therefore estrogen reduction can cause ERs to be unable to normal Activate, play biological effect, so as to cause a series of diseases, including osteoporosis, premature ovarian failure, climacteric metancholia, irregular menstruation, infertility, degenerative disc disease, osteoarthritic inflammation and immunity disease, angiocardiopathy, senile dementia, bone metastaes etc., clinically there is controversies in hormone replacement in the elderly, but side effect is notable.Therefore needing exploitation can be combined with ERs, play biological effect, and adhesion gentle medicine or health food.
The content of the invention
For the above-mentioned deficiency of prior art, embodiments in accordance with the present invention, it is desirable to provide a kind of have the ERs activator of α 36 of competitive activation to ERs, and provides its medical usage.
According to embodiment, the proposition of technical solution of the present invention is, as the ERs activator of α 36, have competitive activation to ERs based on Osthole.
According to one embodiment, the proposition of technical solution of the present invention is based on the discovery that useful effect concentration of the Osthole in the body fluid of affected part is 0.01-10 μM.
According to one embodiment, in technical solution of the present invention, the Osthole is mixed to form various forms of powders, paste, pulvis, injection, aqua, injection or nano material etc. with pharmaceutically acceptable excipient substance.
According to embodiment, the present invention is used as the ERs activator of α 36 by Osthole, with various forms of medicines or health food that Osthole is prepared as principle active component, can be used for preventing and treating above-mentioned estrogen reduction property disease, including osteoporosis, premature ovarian failure, climacteric metancholia, irregular menstruation, infertility, degenerative disc disease, osteoarthritic inflammation and immunity disease, angiocardiopathy, senile dementia, bone metastaes etc..Subcutaneous, intravenous injection or anal intestine can be taken to be administered when in use；The use of parenteral solution can arbitrarily select physiological saline, glucose, stabilizer, preservative, suspending agent or emulsifying agent etc..
Relative to prior art, Osthole is the active principle extracted from Cnidium Monnieri, it is a kind of new ERs activator of α 36, it can be combined with competitiveness with estrogenic receptor subtype α 36, so as to play biological effect, and action temperature and, many side effects that estrin treatment brings can be avoided.Therefore, the various forms of medicines or health food for being prepared as principle active component with Osthole, can be used for preventing and treating above-mentioned estrogen reduction property disease.
Brief description of the drawings
Fig. 1 is the skeleton symbol of Osthole.
Fig. 2 intervenes cell for the Osthole of various concentrations, and after cell cracking, the ERs of α 36 is isotopically labeled ligand binding rate change block diagram.
Fig. 3 is the expression cell species schematic diagram of the ERs of α 36.
Fig. 4 is Osthole by activating the ERs of α 36, the block diagram of suppression osteoclast formation.
Fig. 5 is Osthole by activating the ERs of α 36, the block diagram of suppression osteoclastic bone resorption function.
Specific embodiment
Below in conjunction with the accompanying drawings and specific embodiment, the present invention is expanded on further.These embodiments are interpreted as being merely to illustrate the present invention rather than limit the scope of the invention.After the content for having read record of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalence changes and modification equally fall into the scope of the claims in the present invention.
In following examples of the present invention, Osthole is extracted using commercially available product or according to field of Chinese medicines conventional extraction from warm kidney sun Cnidium Monnieri.M is molar concentration, i.e. mol/L；μM be every liter of micromole.
In following examples of the present invention, the experimental technique not indicated especially, for example isotope marks ligand receptor Binding experiment, Western Blot, osteoclast Differentiation System, bone information experiment, using experimental technique generally in the art.
Embodiment 1
Osthole is a kind of new ERs activator of α 36, has competitive activation to ERs：Osthole (Fig. 1) is the natural products extracted from warm kidney sun Cnidium Monnieri.In research, first by people's Endometrial carcinoma cell line (Ishikawa cell lines), after knocking out erss, the cell only ERs of express alpha 36.Cell is intervened with the Osthole of various concentrations, after cell cracking, is detected by the combination to isotope marks part and acceptor.It was found that Osthole with the ERs of competitive binding α 36 of dose dependent, can show as the part of isotope marks and the ERs Percentage bounds of α 36 gradually reduced as Osthole concentration increases, close to 100% inhibiting rate at 1-10 μM.When i.e. 0.01 μM Osthole intervenes cell, the ERs of α 36 having close to 70% is still isotopically labeled ligand binding, when 0.1 μM of Osthole intervenes cell, the ERs of α 36 only less than 20% is still isotopically labeled ligand binding, and when 1 μM of Osthole intervenes cell, the ERs of α 36 of very low amounts is isotopically labeled ligand binding, when 10 μM of Ostholes intervene cell, there is no that the ERs of α 36 is still isotopically labeled ligand binding, that is 1-10 μM of Osthole can combine the ERs of α 36 (Fig. 2) with perfect competition.According to result, the concentration range of the inhibiting rate of Osthole 100% is at 0.01-10 μM, and action effect is more gentle.
Embodiment 2
Proved by Western Blot first, the main ERs of express alpha high 36 (Fig. 3) in osteoclast.Osteoclast Differentiation System is employed in vitro, demonstrates the biological effect after the ERs of Osthole competitive binding α 36.Separate and cultivate primary monocytes/macrophages, osteoclast formation is induced by RANKL+MCSF, and give gradient Osthole in vitro culture, it was found that big Osthole strengthens the inhibitory action of osteoclast as concentration increases, 0.01 μM of Osthole has slight inhibitory action to osteoclast formation, during to 0.5 μM of Osthole, 50% osteoclast formation can be suppressed, 5-10 μM of Osthole can completely inhibit the formation of osteoclast.Hence it is demonstrated that after Osthole and the combination ERs competitive bindings of α 36, biological effect can be played really, suppress osteoclast formation (Fig. 4).Bone information experiment also demonstrates that 10 μM of Ostholes can completely inhibit the bone information ability (Fig. 5) of osteoclast, such that it is able to be used for the prevention and treatment of estrogen reduction property osteoporosis.By the experiment, proved in bone and its cells, biological effect can be caused really after the ERs of Osthole competitive binding α 36.
Therefore, Osthole can be by activating the ERs of α 36, osteoporosis, premature ovarian failure, climacteric metancholia, irregular menstruation, infertility, degenerative disc disease, osteoarthritic inflammation and immunity disease, angiocardiopathy, senile dementia, bone metastaes that prevention and treatment estrogen reduction causes.Can be used for being made in the medicine or health food for preventing and treating above-mentioned disease.
Claims (6)
1. Osthole as the ERs activator of α 36 purposes.
2. purposes according to claim 1, it is characterized in that, the useful effect concentration of Osthole is 0.01-10
μM。
3. according to the purposes of claim 1 or 2, it is characterized in that, Osthole is subjected to pharmaceutically
Excipient substance be mixed to form powder, paste, pulvis, injection, aqua, injection or nano material.
4. Osthole is preparing anti-curing osteoporosis, ovary morning as the ERs activator of α 36
Decline, climacteric metancholia, irregular menstruation, infertility, degenerative disc disease, osteoarthritic inflammation
In the medicine or health food of immunity disease, angiocardiopathy, senile dementia or bone metastaes
Purposes.
5. purposes according to claim 4, it is characterized in that, the useful effect concentration of Osthole is 0.01-10
μM。
6. the ERs activator of a kind of α 36, it is characterized in that, its active ingredient is Osthole, dense
Spend is 0.01-10 μM.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510934203.2A CN106880627A (en) | 2015-12-15 | 2015-12-15 | Osthole as the ERs activator of α 36 purposes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510934203.2A CN106880627A (en) | 2015-12-15 | 2015-12-15 | Osthole as the ERs activator of α 36 purposes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106880627A true CN106880627A (en) | 2017-06-23 |
Family
ID=59174598
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510934203.2A Pending CN106880627A (en) | 2015-12-15 | 2015-12-15 | Osthole as the ERs activator of α 36 purposes |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106880627A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110711177A (en) * | 2019-09-23 | 2020-01-21 | 山东第一医科大学(山东省医学科学院) | Osthole microemulsion and preparation method and application thereof |
-
2015
- 2015-12-15 CN CN201510934203.2A patent/CN106880627A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| 袁娟丽等: "中药蛇床子药理研究进展", 《广西中医学院学报》 * |
| 鲍君杰: "蛇床子素防治去卵巢大鼠骨质疏松的实验研究", 《中国优秀博硕士学位论文全文数据库（硕士） 医药卫生科技辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110711177A (en) * | 2019-09-23 | 2020-01-21 | 山东第一医科大学(山东省医学科学院) | Osthole microemulsion and preparation method and application thereof |
| CN110711177B (en) * | 2019-09-23 | 2022-03-25 | 山东第一医科大学(山东省医学科学院) | Osthole microemulsion and preparation method and application thereof |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
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Application publication date: 20170623 |