CN102764262A - Application of oleanolic acid and retinoic acid pharmaceutical composition to medicament for treating insulin resistance and diabetes - Google Patents
Application of oleanolic acid and retinoic acid pharmaceutical composition to medicament for treating insulin resistance and diabetes Download PDFInfo
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- CN102764262A CN102764262A CN2012101866178A CN201210186617A CN102764262A CN 102764262 A CN102764262 A CN 102764262A CN 2012101866178 A CN2012101866178 A CN 2012101866178A CN 201210186617 A CN201210186617 A CN 201210186617A CN 102764262 A CN102764262 A CN 102764262A
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Abstract
The invention discloses application of an oleanolic acid and retinoic acid pharmaceutical composition to medicament for treating insulin resistance and diabetes. Intraperitoneal injection of the oleanolic acid and retinoic acid pharmaceutical composition to diabetic animal can significantly lower the blood glucose level; and addition of the oleanolic acid and retinoic acid pharmaceutical composition in culture solution for culturing liver cells can significantly promote transmission of an insulin signal. Therefore, the oleanolic acid and retinoic acid pharmaceutical composition can be applied to medicaments for treating diabetes, insulin resistance and metabolic syndrome closely related to insulin resistance.
Description
Technical field
The present invention relates to the purposes of oleanolic acid and retinoic acid drug regimen, specifically refer to the application in treatment insulin resistant and diabetes medicament of oleanolic acid and retinoic acid drug regimen.
Background technology
In recent years, the transformation of Along with people's life style, the sickness rate of diabetes increases year by year.ADA infers that to the year two thousand thirty, the whole world will have 3,500,000,000 people to suffer from diabetes and complication thereof.Recently, an investigation of China shows that China's diabetes number of patients has reached 9,200 ten thousand at present, is only second to India.Diabetes have produced huge pressure to the economic development in the whole world especially developing country, and according to statistics, the expense expenditure that developing country is used for the diabetes aspect has exceeded 10% of health expense budget.Be the type 2 diabetes mellitus patient more than 90% in the diabetics, insulin resistant is the basic feature of type 2 diabetes mellitus.Insulin resistant is meant the target tissue of insulin actions such as liver, muscle, fat, can not respond the pathological state that hypoglycemic activity that insulin causes insulin weakens even lacks.Except that type 2 diabetes mellitus, insulin resistant is also closely related with the incidence and development of hypertension, atherosclerosis, metabolism syndrome, ovarian cyst, Alzheimer's disease, tumor.Therefore, mechanism of insulin resistance and study on prevention are seemed particularly important.At present, the active drug that is used to treat insulin resistant and diabetes mainly comprises thiazolidinediones medicine and metformin etc., and the Liver and kidney toxicity of these medicines is bigger.
In normal insulin signaling conduction, insulin and its receptors bind startup insulin signaling, activated receptor endogenous protein tyrosine kinase activity causes the tyrosine phosphorylation of recipient cell kytoplasm one side.Activated receptor is raised again and a series of substrate molecules of phosphorylation conversely.And then the activation phosphatidylinositol-3-kinase (Phosphoinositide-3-kinase, PI3K)/protein kinase B (Protein kinase B, Akt).Protein kinase B is a kind of important kinases in the insulin signaling conductive process, and whether normally the height of its phosphorylation level often is used as insulin signaling conduction index under the insulin stimulating condition.When insulin resistant took place, the protein kinase B phosphorylation level of insulin stimulating obviously reduced.
(Oleanolic acid is a kind of natural triterpenoid OA), and is the aglucon of many saponin that its structural formula is seen Fig. 1 to oleanolic acid.Oleanolic acid is present in the various foods (rapeseed oil) in a large number, and is the composition of many plant leafs and rhizome, comprises that Olea europaea, Viscum album L., Aralia chinensis L and other surpass 120 kinds of natural plants.Oleanolic acid has had the use in more than 20 year historical as Effective Components of Chinese Herb, is mainly used in the treatment viral hepatitis.Discover that oleanolic acid can protect mice to avoid various hepatotoxicants and electrophilic thing, comprise the damage of carbon tetrachloride, acetaminophen, bromination benzene and thioacetamide etc.After giving oleanolic acid, oleanolic acid mainly is distributed in liver and at liver metabolism.Mice gives oleanolic acid in advance, can reduce the transaminase's that hepatotoxicant causes rising and suppress central necrosis of hepatic lobule.In addition, there is a large amount of research report to be rich in the natural drug of oleanolic acid and the synthesis of derivatives of oleanolic acid shows a series of pharmacology's function, comprises effects such as antiinflammatory, antitumor, promotion apoptosis.
(retinoic acid RA), claims tretinoin, vitamin A acid, tretinoin etc. again to retinoic acid, is the metabolic intermediate of vitamin A in the animal body, and its structural formula is seen Fig. 2.Physiology and pharmacological activity are widely arranged.Beta-carotene is generated the retinol of 2 molecules, i.e. vitamin A at intestinal by the oxidation of intestinal mucosa beta-carotene oxygenase.The latter is absorbed into and is oxidized to retinal in the body. further be oxidized to tretinoin (being retinoic acid) again.
Summary of the invention
The objective of the invention is oleanolic acid and retinoic acid drug regimen are applied to treat in the medicine of insulin resistant and diabetes.
For realizing the foregoing invention purpose, technical scheme of the present invention is following:
A kind of compositions that is used to treat insulin resistant and diabetes, said composition comprise oleanolic acid and retinoic acid medicine.
The purposes of a kind of oleanolic acid and retinoic acid drug regimen is used for treating the medicine of insulin resistant and diabetes.
Mensuration result of the present invention shows: in diabetes rat, oleanolic acid and retinoic acid can make blood glucose reduce, and it is more obvious that oleanolic acid and retinoic acid Combined application reduce blood glucose.In oleanolic acid and the retinoic acid cultured cell; The protein kinase B phosphorylation level of insulin stimulating significantly strengthens; The obviously reduction of the protein kinase B phosphorylation level of inhibited oxidation stress-induced, thus oleanolic acid and the effectiveness of retinoic acid Combined application in treatment insulin resistant and diabetes verified.
Characteristics of the present invention are for using oleanolic acid and the retinoic acid Combined application with the effectiveness of protecting the liver; Treatment insulin resistant and diabetes; Compare with existing Remedies for diabetes, both guaranteed to improve insulin resistant and hypoglycemic effectiveness, can bring into play the effectiveness that protects the liver of oleanolic acid again.
Description of drawings
Fig. 1 is the oleanolic acid structural formula.
Fig. 2 is the retinoic acid structural formula.
Fig. 3 is oleanolic acid and retinoic acid Combined application blood sugar decreasing effect figure.
Fig. 4 is that oleanolic acid and retinoic acid Combined application strengthen protein kinase B phosphorylation figure.
The specific embodiment
Through instance the present invention is further specified below, its purpose is better to understand content of the present invention, and unrestricted protection scope of the present invention.
Embodiment
1. experimental apparatus
Blood sugar detection appearance (Johnson Co.), precise electronic balance, 1ml syringe etc.
2. laboratory animal and material
2.1 laboratory animal
The SD rat, the cleaning level, male, body weight 180 ± 220g has The Fourth Military Medical University's Experimental Animal Center to provide.
BRL-3A rat normal liver cell system purchases the cell classical collection center in Wuhan.
2.2 experiment material
Normal saline, picric acid, blood sugar test paper, insulin.
3. experimental technique
Select 40 SD rats for use, cleaning level, male, body weight 180 ± 220g are divided into normal control group (8) and model group (32) at random, respectively labelling.Model group animal lumbar injection streptozotocin makes up diabetes animal model.Treat that the model group animal blood glucose raises; After reaching the diabetes diagnosis standard; The model group animal is divided into positive controls (8), oleanolic acid treatment group (8), retinoic acid treatment group (8) and oleanolic acid and retinoic acid therapeutic alliance group (8) at random; Oleanolic acid treatment treated animal lumbar injection every day 20mg/kg oleanolic acid; Retinoic acid treatment treated animal lumbar injection every day 20mg/kg retinoic acid treatment group, oleanolic acid and retinoic acid therapeutic alliance group lumbar injection every day 10mg/kg oleanolic acid and 10mg/kg retinoic acid (both mass ratioes are 1: 1) continued for 2 weeks.The positive control treated animal is injected the administration solvent of same volume.After 2 weeks, measure fasting blood glucose level.
With DMEM culture medium (adding 10% hyclone) culture of rat normal liver cell system (BRL-3A) in 6 orifice plates; When cell grows to 80-90% density, change serum-free DMEM culture medium into, with the oleanolic acid of serum-free DMEM culture medium dissolving variable concentrations and retinoic acid cultured cell 24 hours; After cultivating end; With 100nM insulin stimulating 15 minutes, add cell lysis buffer solution, collect cell lysis; Carry out Protein Detection (Western blot), measure the phosphorylation level of protein kinase B.
4. experimental result
4.1 it is as shown in Figure 3; The average fasting blood sugar of positive treated animal is 24.62 ± 2.26mmol/L; The average fasting blood sugar of oleanolic acid treatment treated animal is 20.06 ± 1.48mmol/L; The average fasting blood sugar of retinoic acid treatment treated animal is 20.36 ± 1.04mmol/L, and oleanolic acid and the average fasting blood sugar of retinoic acid therapeutic alliance treated animal are 12.30 ± 3.23mmol/L.
4.2 as shown in Figure 4, to compare with normal control, the protein kinase B phosphorylation level of oleanolic acid and retinoic acid Combined Treatment group insulin stimulating obviously increases.
In addition, the mass percent that oleanolic acid and retinoic acid is taken at respectively in the compositions is 40% and 60%; The mass percent that oleanolic acid and retinoic acid are taken at respectively in the compositions is 60% and 40%; Compositions to above-mentioned two kinds of different components makes an experiment, and compares with single use oleanolic acid or retinoic acid and has obtained effect preferably equally.
It is thus clear that it is feasible that the present invention utilizes oleanolic acid and retinoic acid to unite to be used for the medicine of treating insulin resistant and diabetes.
Claims (4)
1. compositions that is used to treat insulin resistant and diabetes, it is characterized in that: said composition is made up of oleanolic acid and retinoic acid.
2. compositions according to claim 1 is characterized in that: the mass percent of oleanolic acid in compositions is 40%-60%; The mass percent of retinoic acid in compositions is 40%-60%.
3. compositions according to claim 1 is characterized in that: oleanolic acid, the retinoic acid mass percent in compositions is 50%.
4. oleanolic acid and the retinoic acid compositions purposes in the medicine of treatment insulin resistant and diabetes.
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| CN 201210186617 CN102764262B (en) | 2012-06-07 | 2012-06-07 | Application of oleanolic acid and retinoic acid pharmaceutical composition in medicament for treating insulin resistance and diabetes |
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| CN 201210186617 CN102764262B (en) | 2012-06-07 | 2012-06-07 | Application of oleanolic acid and retinoic acid pharmaceutical composition in medicament for treating insulin resistance and diabetes |
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| CN102764262A true CN102764262A (en) | 2012-11-07 |
| CN102764262B CN102764262B (en) | 2013-11-06 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103585161A (en) * | 2013-10-25 | 2014-02-19 | 中国人民解放军第四军医大学 | Medicinal composition, and its application in preparation of medicines for treating obesity, insulin resistance and diabetes |
| CN104771403A (en) * | 2014-01-10 | 2015-07-15 | 中国药科大学 | Pharmaceutical composition containing oleanolic acid, and applications thereof in treating diabetes |
| CN107022546A (en) * | 2016-02-01 | 2017-08-08 | 华东师范大学 | A kind of gene loop induced expression regulates and controls method |
| CN116421657A (en) * | 2022-12-30 | 2023-07-14 | 陈寿兵 | Pharmaceutical composition for treating diabetes insulin resistance |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1237897A (en) * | 1996-09-27 | 1999-12-08 | 尤尼利弗公司 | Skin care compositions containing acid and retinoid |
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2012
- 2012-06-07 CN CN 201210186617 patent/CN102764262B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1237897A (en) * | 1996-09-27 | 1999-12-08 | 尤尼利弗公司 | Skin care compositions containing acid and retinoid |
Non-Patent Citations (2)
| Title |
|---|
| 沈晓霞等: "维甲酸与糖尿病及并发症的研究", 《医学综述》 * |
| 高大威: "齐墩果酸抗糖尿病作用及其机理研究", 《中国博士学位论文全文数据库医药卫生科技辑》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103585161A (en) * | 2013-10-25 | 2014-02-19 | 中国人民解放军第四军医大学 | Medicinal composition, and its application in preparation of medicines for treating obesity, insulin resistance and diabetes |
| CN103585161B (en) * | 2013-10-25 | 2015-12-02 | 中国人民解放军第四军医大学 | Pharmaceutical composition and the application in preparation treatment obesity, insulin resistant and diabetes medicament thereof |
| CN104771403A (en) * | 2014-01-10 | 2015-07-15 | 中国药科大学 | Pharmaceutical composition containing oleanolic acid, and applications thereof in treating diabetes |
| CN107022546A (en) * | 2016-02-01 | 2017-08-08 | 华东师范大学 | A kind of gene loop induced expression regulates and controls method |
| CN116421657A (en) * | 2022-12-30 | 2023-07-14 | 陈寿兵 | Pharmaceutical composition for treating diabetes insulin resistance |
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| CN102764262B (en) | 2013-11-06 |
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