CN106539809A - Purposes of the peoniflorin in the medicine for preparing treatment or prevention angiopathy - Google Patents
Purposes of the peoniflorin in the medicine for preparing treatment or prevention angiopathy Download PDFInfo
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- CN106539809A CN106539809A CN201611007057.XA CN201611007057A CN106539809A CN 106539809 A CN106539809 A CN 106539809A CN 201611007057 A CN201611007057 A CN 201611007057A CN 106539809 A CN106539809 A CN 106539809A
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- purposes
- peoniflorin
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
Abstract
The present invention relates to the purposes of field of traditional Chinese, more particularly to peoniflorin in preparing treatment or preventing angiopathy medicine；Jing present invention checkings; peoniflorin can promote PPAR α up-regulated expressions; suppress expression of apoptosis protein; and suppress myocardial cell autophagy; so as to inhibitory activity oxygen injury causes cardiomyocyte cell death, promote myocyte survival, with protection and treatment double utility; therefore, peoniflorin has the purposes of the medicine for preparing treatment or preventing chronic peripheral vascular occlusive disease.As peoniflorin is structure clearly single component, present invention discover that and clearly explain the mechanism of its protecting myocardial cell, be to develop the standardization of Chinese medicine preparation based on peoniflorin and internationalization lays the foundation；Known peoniflorin is without obvious toxic and side effects, more advantageous than single Western medicine simultaneously, can be used in combination with Western medicine, reduces the toxic and side effects of Western medicine.
Description
Technical field
The present invention relates to field of traditional Chinese, more particularly to peoniflorin are in preparing treatment or preventing angiopathy medicine
Purposes.
Background technology
As China's economy constantly develops, the quick raising of the living standard of people, while the aggravation of social senilization, the heart
The pathogenicity rate of cerebrovascular disease is presented and rises situation, and the cause of disease includes hypertension, hyperlipidemia, coronary atherosclerosiies, blood vessel wall
Smooth muscle abnormal metabolism, diabetes etc..And cardiovascular and cerebrovascular disease also becomes current first dead " killer ".The heart, cerebral arterieies are hard
Change can cause cerebral infarction, coronary atherosclerosiies to cause coronary atherosclerotic myocardial ischemia-anoxemia, so as to draw
The heart disease generally existing for rising, while coronary atherosclerosiies can cause coronary artery blockage to form coronary heart disease, and most
For one of common cardiovascular disease.Myocardial ischemia causes cardiomyocyte cell death, so as to cause cardiac arrest or cardiac muscle to lack
Courageous and upright mortality risk.
Prevention and treatment cardiovascular and cerebrovascular disease mainly has two big class of Chinese patent medicine and Western medicine at present.Chinese medicine mainly has the step-length brain heart
Logical, Wei Zhen Zhu Wan, Sanqitongshu capsule, brain-invigorating and heart-soothing capsule, SHENFU ZHUSHEYE, FUFANG DANSHEN JIAONANG etc.；Western medicine has Rui De
Bright, En Bipu, triflusal capsule etc..The single using effect of Western medicine is typically undesirable, is usually used in combination with Chinese medicine.Current medicine
Thing has different degrees of curative effect to cardiovascular and cerebrovascular disease, but due to cardiovascular and cerebrovascular disease complex genesis, existing medicine shows
Respective defect.Western medicine usually acts on relatively single, while having some side effect, it has to be used in combination by Chinese medicine；In
Patent medicine is particular about compatibility, reduces side effect, improves therapeutic effect, but also because complicated component, cure mechanism is difficult to illustrate, serious shadow
Ring standardization and the internationalization to Chinese patent medicine.
The target drug to suppress myocardial cell ischemic dead is occurred in that in recent years.Such as nuclear receptor albumen PPAR α
Cardiomyocyte cell death can be significantly inhibited, its activation energy strengthens myocardial cell external world adverse environment and stimulates lower cell survival rate, so as to
Strengthen Patients with geriatric cardiovascular and cerebrovascular diseases survival rate.It has been found that peoniflorin can be by raising myocardial cell peroxisome proliferation
Thing activated receptor alpha（PPARα）Expression, and then substantially reduce the death of the myocardial cell caused because of anoxia.
Peoniflorin（paeoniflorin）, its structural formula is：
The molecular formula of the compound is C23H28O11, it is the amorphous chocolate brown powder of hygroscopicity（90% is off-white powder）, [α]
16D-12.8.（C=4.6, methanol）, four acetates be colorless needle crystals, fusing point：196℃.Under sour environment, paeoniflorin is steady
It is fixed（PH2～6）, it is unstable under alkaline environment.It is that one kind has expansion of blood vessels, antalgic and sedative, antiinflammatory antiulcer, solution pyrolysis
Convulsion, the Chinese medicine of diuresis.
The pharmacological action for being currently known peoniflorin has：（1）With antitumor action；（2）With blood pressure lowering, resist myocardial ischemia
And Arrhythmia；（3）Act on expansion of blood vessels；（4）Act on lipidemia；（7）Prevent alloxan from raising blood
The effect of sugar；（5）With analgesia, calm, anticonvulsant action.
The content of the invention
It is an object of the invention to overcome defect present in prior art, there is provided peoniflorin is preparing treatment angiopathy
Purposes in medicine.
Jing applicant's experimental verification, peoniflorin can raise myocardial cell peroxisome proliferator-activated receptor alpha
（PPARα）Expression, and then substantially reduce the death of the myocardial cell caused because of anoxia.
The invention discloses purposes of the peoniflorin in the medicine for being used to treating or prevent cardiovascular and cerebrovascular disease is prepared.
The invention discloses use of the peoniflorin in the medicine for being used to treating or prevent arterial obliterans of lower extremity is prepared
On the way.
The invention discloses purposes of the peoniflorin in the medicine for being used to recovering and improve ischemic tissue's blood flow is prepared.
The invention discloses purposes of the peoniflorin in the medicine for being used to preventing or treat diabetic foot disease is prepared.
The invention discloses purposes of the peoniflorin in the medicine for being used to promoting endogenic blood vessel bypass to be formed is prepared.
The invention discloses peoniflorin is being prepared for promoting in the medicine that collateral systemic vascular is formed around ischemic tissue
Purposes.
The invention discloses purposes of the peoniflorin in the medicine for being used to treating or prevent thromboangiitis obliteranss is prepared.
Compared with prior art, beneficial effects of the present invention are as follows：
The invention discloses purposes of the peoniflorin in medicine is prepared.As peoniflorin can promote PPAR α up-regulated expressions, suppress
Expression of apoptosis protein, and suppress myocardial cell autophagy, so as to inhibitory activity oxygen injury causes cardiomyocyte cell death, promote cardiac muscle thin
Born of the same parents are survived, with protection and treatment double utility, therefore, peoniflorin has preparation treatment or preventing chronic peripheral occlusive
The purposes of the medicine of disease.As peoniflorin is structure clearly single component, present invention discover that and clearly explaining its guarantor
The mechanism of shield heart myocyte, is to develop the standardization of Chinese medicine preparation based on peoniflorin and internationalization lays the foundation；It is simultaneously known
Peoniflorin is without obvious toxic and side effects, more advantageous than single Western medicine, can be used in combination with Western medicine, reduces the secondary work of poison of Western medicine
With.
Description of the drawings
In order to be illustrated more clearly that the embodiment of the present invention or technical scheme of the prior art, below will be to embodiment or existing
Accompanying drawing to be used needed for having technology description is briefly described, it should be apparent that, drawings in the following description are only this
Some embodiments of invention, for those of ordinary skill in the art, on the premise of not paying creative work, can be with
Other accompanying drawings are obtained according to these accompanying drawings.
Fig. 1 is peoniflorin addition and H2O2Induction H9c2 cytoprotectives affect graph of a relation；
Fig. 2 is peoniflorin addition and H2O2The graph of a relation of induction H9c2 cell anti-apoptotic proteins；
Fig. 3 is that peoniflorin/PPAR α suppress H2O2Induction H9c2 cell death graphs of a relation；
Graphs of a relation of the Fig. 4 for peoniflorin activation/PPAR α/autophagy signal.
Specific embodiment
Below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is carried out clear, complete
Site preparation is described, it is clear that described embodiment is only a part of embodiment of the invention, rather than the embodiment of whole.It is based on
Embodiment in the present invention, it is every other that those of ordinary skill in the art are obtained under the premise of creative work is not made
Embodiment, belongs to the scope of protection of the invention.
The present invention has excavated new medical application to known compound peoniflorin, has opened up a new application.Tool
Body ground, due to cell peroxidase body proliferator activated receptor α（PPARα）Expression of apoptosis protein can be suppressed, and suppress cardiac muscle
Cell autophagy, so as to protecting myocardial cell active oxygen induced damage, maintains myocardial function.Improve and recover ischemic tissue's blood flow,
These effects are conducive to treating and preventing cardiovascular and cerebrovascular disease.
It will be appreciated by persons skilled in the art that peoniflorin abundance, can make peroral dosage form, injection type, piece
Dosage form etc., easy to use, injection can make intramuscular injection and acupoint injection therapy, can make intravenous injection.
Need further exist for explanation, the various terms that use of the present invention and phrase have well known to a person skilled in the art
General sense, nonetheless, the present invention remains desirable to these terms and phrase are described in more detail and explained at this, refers to
Term and phrase if any inconsistent with common art-recognized meanings, be defined by the implication stated by the present invention.
The present invention to used in test to material and test method carry out generality and/or specific describe.Though
So to realize that but many materials that the object of the invention used and operational approach are it is known in the art that the present invention still here
Describe in detail as far as possible.It will be apparent to those skilled in the art that hereinafter, if not specified, material therefor of the present invention and
Operational approach is well known in the art.
Peoniflorin employed in following each embodiments is purchased from Sigma-Aldrich, Cat. No. P0038；PPARα
ShRNA is bought in Shanghai JiKai Gene Chemical Technology Co., Ltd.Certainly those skilled in the art can also pass through other ways
Footpath for example, is extracted from Paeoniaceae plant roots using prior art obtaining peoniflorin, and here of the present invention is not especially limited.
The peoniflorin obtained using other approach carries out following each embodiments, as long as dosage is torn open is counted as equivalent.
H9c2 cells are H9c2 (2-1) ATCC® Number: CRL-1446™。
Embodiment 1：Peoniflorin is to H2O2The protective effect of the anoxia H9c2 cell of induction
H9c2 cells are with containing 10% hyclone（FBS）DMEM complete medium cellar cultures, under microscope, microscopy melts up to 80%
When right, digested with 0.25% pancreatin, with every hole 5 × 105Individual cell is inoculated in 6 orifice plates, is placed in 37 C, 5% CO2Incubator
After middle culture 48h, the peoniflorin that whole molar concentration is 0,0.1,0.5,1 M is separately added into（Culture medium is dissolved in, similarly hereinafter）, per group
It is repeated 3 times.The peoniflorin of variable concentrations acts on H9c2 cell 6h, is rinsed with 200 μ L cold PBS, is repeated 3 times, and thoroughly removes
Culture medium.Cell 0.5mM H2O2Cell survival is analyzed using MTT after induction 6h.As a result it is as shown in Figure 1（Numerical value mean ±
Standard deviation (mean ± SD) expression, n=3； *P<0.05, compared with blank control group, peoniflorin significantly improves H2O2Cause anoxia
Under myocyte survival rate, show under anoxic conditions, peoniflorin has very strong protective effect to myocardial cell.
Embodiment 2：Peoniflorin is to H2O2The impact of induction H9c2 apoptosis protein expression
H9c2 cells are with containing 10% hyclone（FBS）DMEM complete medium cellar cultures, under microscope, microscopy melts up to 80%
When right, digested with 0.25% pancreatin, with every hole 5 × 105Individual cell is inoculated in 6 orifice plates, is placed in 37 C, 5% CO2Incubator
After middle culture 48h, the peoniflorin that whole molar concentration is 0,0.5 M is separately added into, is repeated 3 times per group.Peoniflorin acts on H9c2
Cell 6h, is rinsed with 200 μ l cold PBS, is repeated 3 times, thoroughly removes culture medium.Cell 0.5mM H2O2After induction 6h, carefully
Cellular lysate, Western blot analysis specific protein expression, as a result as shown in Figure 2.As a result show, peoniflorin is substantially reduced
H2O2The expression of the apoptosis protein of induction, anti-apoptotic proteins up-regulated, disclosing peoniflorin in protein level can be by suppressing
Apoptosis, play protection mechanism to myocardial cell.The albumen of wherein anti-apoptotic has Mcl-1, Bcl2, Bcl-XL；Promote
Apoptotic albumen has Bad, Bax；Indicate that apoptotic albumen has Cleaved caspase, Cleaved PARP-1；This
Albumen internal reference Actin in embodiment.
Embodiment 3：Peoniflorin/PPAR alpha signals suppress H2O2The impact of induction H9c2 cell deaths
H9c2 cells are with containing 10% hyclone（FBS）DMEM complete medium cellar cultures, under microscope, microscopy melts up to 80%
When right, digested with 0.25% pancreatin, cell is inoculated in 96 orifice plates, is placed in 37 C, 5% CO2After 48h is cultivated in incubator,
Cell transfecting compares shRNA, and PPAR α shRNA were separately added into the peoniflorin 6 that whole molar concentration is 0.5 M little after 36 hours
When, it is repeated 3 times per group.Rinsed with 200 μ l cold PBS, be repeated 3 times, thoroughly remove culture medium.Cell is lured with 0.5mM H2O2
Cell survival is analyzed using MTT after leading 6h, as a result as shown in Figure 3.As a result show, peoniflorin can not play the guarantor to myocardial cell
Shield is acted on；And do not receive under other disturbed conditions in PPAR α, peoniflorin can significantly improve myocyte survival rate, and this result enters one
Step is disclosed, and peoniflorin is to play a part of protecting myocardial cell by PPAR α.Non- spies of the Ctl RNA for PPAR α shRNA in figure
Different matched group；PPAR α shRNA are that specificity suppresses PPAR alpha expression experimental grouies.
Embodiment:4：Peoniflorin activates PPAR α/autophagy signal
H9c2 cells are with containing 10% hyclone（FBS）DMEM complete medium cellar cultures, under microscope, microscopy melts up to 80%
When right, digested with 0.25% pancreatin, with every hole 5 × 105Individual cell is inoculated in 6 orifice plates, is placed in 37 C, 5% CO2Incubator
After middle culture 48h, the peoniflorin that whole molar concentration is 0.5 M is separately added into, is repeated 3 times per group.It is thin that peoniflorin acts on H9c2
Born of the same parents 6h, is rinsed with 200 μ l cold PBS, is repeated 3 times, thoroughly removes culture medium.Cell is with 0.5 mM H2O2After induction 6h, cell
Cracking, Western blot analysis PPAR α/autophagy signal related protein expression, as a result as shown in Figure 4.Experimental result shows
Show, peoniflorin can significantly improve the expression of PPAR α under anoxic conditions, meanwhile, cell autophagy is also suppressed；And artificially suppressing
During PPAR alpha expressions, peoniflorin can not raise PPAR alpha expressions, and cell autophagy can not be suppressed；This experiment is from protein level solution
The phenomenon in embodiment 3 is released, peoniflorin is disclosed and myocardial cell protection is acted on, be by raising PPAR alpha expressions, suppressing cell
The mechanism of the cell death that autophagy causes.Nonspecific controls of the Ctl RNA for PPAR α shRNA in figure；PPAR α shRNA are spy
The opposite sex suppresses PPAR alpha expression reagents；LC3-1, LC3-2 are cell autophagy Mark；GAPDH is albumen internal reference.
Hyclone Fetal Bovine Serum（FBS）Those skilled in the art are all with DMEM complete mediums to commonly use
Medicine, prepare and using method be all general knowledge known in this field.
The PBS is phosphate buffered saline(PBS)（phosphate buffer saline）, those skilled in the art generally make
With sodium ascorbyl phosphate buffer solution or potassium phosphate buffer solution.The cold phosphate buffered saline(PBS) can be by phosphate buffer solution ice
Bath or in refrigerator 4 C cold preservations realizing.
Presently preferred embodiments of the present invention is the foregoing is only, protection scope of the present invention is not intended to limit.It is all
Any modification, equivalent substitution and improvements made within the spirit and principles in the present invention etc., are all contained in protection scope of the present invention
It is interior.
Claims (10)
1. peoniflorin is preparing the purposes in treating or preventing angiopathy medicine.
2. purposes according to claim 1, it is characterised in that the purposes is that peoniflorin is preparing treatment or preventing heart and brain
Purposes in angiopathy medicine.
3. purposes according to claim 2, it is characterised in that the purposes is that peoniflorin is preparing treatment or preventing because scarce
Purposes in the dead medicine of the myocardial cell that oxygen causes.
4. purposes according to claim 1, it is characterised in that the purposes be peoniflorin prepare for prepare treatment or
Purposes in the medicine of prevention arterial obliterans of lower extremity.
5. purposes according to claim 1, it is characterised in that the purposes is peoniflorin recover for preparing preparing and
Improve the purposes in the medicine of ischemic tissue's blood flow.
6. purposes according to claim 1, it is characterised in that the purposes be peoniflorin prepare for prepare prevention or
Purposes in the medicine for the treatment of diabetic foot disease.
7. purposes according to claim 1, it is characterised in that the purposes is peoniflorin to be prepared in preparing and promoting
Purposes in the medicine that the blood vessel bypass of source property is formed.
8. purposes according to claim 1, it is characterised in that the purposes is peoniflorin to be promoted to lack for preparing preparing
Purposes in the medicine that collateral systemic vascular is formed around haemal tissue.
9. purposes according to claim 1, it is characterised in that the purposes be peoniflorin prepare for prepare treatment or
Purposes in the medicine of prevention thromboangiitis obliteranss.
10. the purposes of the peoniflorin according to claim 1-9 any one, it is characterised in that effective use of peoniflorin
Dose concentration scope is 0.1-1 M.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611007057.XA CN106539809A (en) | 2016-11-16 | 2016-11-16 | Purposes of the peoniflorin in the medicine for preparing treatment or prevention angiopathy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201611007057.XA CN106539809A (en) | 2016-11-16 | 2016-11-16 | Purposes of the peoniflorin in the medicine for preparing treatment or prevention angiopathy |
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| CN201611007057.XA Pending CN106539809A (en) | 2016-11-16 | 2016-11-16 | Purposes of the peoniflorin in the medicine for preparing treatment or prevention angiopathy |
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Citations (4)
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|---|---|---|---|---|
| CN1443539A (en) * | 2003-04-07 | 2003-09-24 | 江苏正大天晴药业股份有限公司 | Medicine composition of red peony total glucoside for curing cardio-cerebrovascular diseases and its preparation method |
| CN103830255A (en) * | 2012-11-26 | 2014-06-04 | 青岛百草汇中草药研究所 | Application of paeoniflorin in preparation of medicines for treating cerebrovascular diseases |
| CN104666323A (en) * | 2013-11-27 | 2015-06-03 | 周亚伟 | Novel use of paeoniflorin or its derivative or salt |
| CN105796581A (en) * | 2016-03-13 | 2016-07-27 | 长春中医药大学 | Application of paeoniflorin to preparation of medicine for regulating and controlling cholinergic anti-inflammatory pathway |
-
2016
- 2016-11-16 CN CN201611007057.XA patent/CN106539809A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1443539A (en) * | 2003-04-07 | 2003-09-24 | 江苏正大天晴药业股份有限公司 | Medicine composition of red peony total glucoside for curing cardio-cerebrovascular diseases and its preparation method |
| CN103830255A (en) * | 2012-11-26 | 2014-06-04 | 青岛百草汇中草药研究所 | Application of paeoniflorin in preparation of medicines for treating cerebrovascular diseases |
| CN104666323A (en) * | 2013-11-27 | 2015-06-03 | 周亚伟 | Novel use of paeoniflorin or its derivative or salt |
| CN105796581A (en) * | 2016-03-13 | 2016-07-27 | 长春中医药大学 | Application of paeoniflorin to preparation of medicine for regulating and controlling cholinergic anti-inflammatory pathway |
Non-Patent Citations (3)
| Title |
|---|
| 吴永贵等: "《当代内科学进展》", 31 January 2016, 合肥：安徽科学技术出版社 * |
| 宋献美等: "芍药苷对过氧化氢损伤的人脐静脉内皮细胞的保护作用", 《现代预防医学》 * |
| 高宇勤等: "芍药苷预处理激活AMPKα对在体大鼠心肌缺血再灌注损伤的保护作用", 《海南医学》 * |
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