CN106420697A

CN106420697A - Polymethoxylated flavone, composition and application of polymethoxylated flavone preparation in preventing or treating diabetes

Info

Publication number: CN106420697A
Application number: CN201610827938.XA
Authority: CN
Inventors: 郑国栋; 刘鄂湖; 韦敏燕
Original assignee: Guangzhou Medical University
Current assignee: Guangzhou Medical University
Priority date: 2016-09-18
Filing date: 2016-09-18
Publication date: 2017-02-22
Anticipated expiration: 2036-09-18
Also published as: CN106420697B

Abstract

The invention discloses a polymethoxylated flavone, a composition and application of the polymethoxylated flavone preparation in preventing or treating diabetes. The active component of the medicine for preventing and treating diabetes comprises a polymethoxylated flavone and a pharmaceutically acceptable carrier or excipient which are made into a pharmaceutically acceptable preparation formulation, wherein the polymethoxylated flavone is 3,5,6,7,8,3',4'-heptamethoxyflavone. The invention proves that the 3,5,6,7,8,3',4'-heptamethoxyflavone can effectively improve the fasting blood glucose level increase of the high-fat-diet-induced diabetes model and improve the Type II diabetes mainly characterized in impaired glucose tolerance reduction and insulin sensitivity reduction, and thus, can be used for treating and preventing diabetes.

Description

A kind of polymethoxyflavone, compositionss and its preparation are used for preventing or treating diabetes Purposes

Technical field

The invention belongs to field of medicaments, is related to the new application of natural product, and in particular to a kind of polymethoxyflavone, combination Thing and its preparation are used for preventing or treating the purposes of diabetes.

Background technology

Diabetes are one kind as defect of insulin secretion (type i diabetes) or insulin resistant (type ii diabetes) are with height The incretion metabolism disease that blood glucose is characterized, has become the third-largest harm human health for being only second to cardiovascular disease and cancer Disease.2015, the report that IDF (IDF) issues claimed the whole world to there are about 4.15 hundred million adults with glycosuria Disease, it is contemplated that there are about 5 million peoples dead because of diabetes.Treatment type ii diabetes mainly adopt diet, exercise therapy, sulfonylurea at present Class, meglitinide, biguanideses, thiazolidinedioneses, alpha-glucosaccharase inhibitor, insulin etc., but due to diabetes pathology, Etiological study is so far also without substantial breakthrough, and patient continuously emerges cardiovascular pathological changes, kidney while long-term taking Western medicine The complication such as disease of ZANG-organs change, neuropathy.Therefore the newtype drug of research and development effectively treatment diabetes has important clinical meaning.

Polymethoxyflavone (PolymethoxylatedFlavones, PMFs) is that a class contains multiple methoxyl groups, low pole Property, the flavones ingredient for having strong biological activity with planar structure, are 3 in phenyl chromone structure, 4,5,6,7, 4 or more than 4 methoxyl groups are connected with the positions such as 8,2', 3', 4', 5', 6', are mainly derived from Rutaceae Citrus, are present in In the medical materials such as Pericarpium Citri Reticulatae, Pericarpium Citri Reticulatae Viride, Exocarpium Citri Rubrum, Fructus Citri Sarcodactylis, Fructus Aurantii Immaturus.3,5,6,7,8,3', 4'- Heptamethoxyflavone (HMF) is exactly wherein one Kind, its molecular formula is C₂₂H₂₄O₉, it is 1178-24-1 that relative molecular mass is 432.43, No. CAS, and chemical constitution is as follows：

Content of the invention

It is an object of the invention to provide a kind of polymethoxyflavone, compositionss and its preparation are used for preventing or treating diabetes Purposes, the polymethoxyflavone be 3,5,6,7,8,3', 4'- Heptamethoxyflavone (HMF).

Above-mentioned purpose is achieved by the following technical solution：

A kind of medicine for preventing or treating diabetes, active component includes polymethoxyflavone.

Preferably, the polymethoxyflavone is 3,5,6,7,8,3', 4'- Heptamethoxyflavone.

Preferably, the active component also includes Radix Polygalae mouth diphenylene ketone oxide, is polymethoxyflavone and the combining of Radix Polygalae mouth diphenylene ketone oxide Thing.

A kind of pharmaceutical preparation for preventing or treating diabetes, including above-mentioned active component, also includes pharmaceutically permissible The carrier of acceptance or excipient, make pharmaceutically acceptable dosage form.

Preferably, the pharmaceutically acceptable carrier or excipient include one or more solid, semi-solid or liquid Body adjuvant.

Preferably, the pharmaceutically acceptable dosage form includes tablet, dispersible tablet, capsule, soft capsule, microcapsule Agent, granule, injection, injectable powder, lyophilized injectable powder, pellet, drop pill, syrup, powder, extractum, soft extract, mouth Take liquid preparation.

Beneficial effects of the present invention：

The invention demonstrates that, 3,5,6,7,8,3', 4'- Heptamethoxyflavone can be effectively improved the glycosuria of high fat diet induction The fasting blood sugar level of disease model is raised, and improves the II type sugar for being reduced to principal character with impaired glucose tolerance and insulin sensitivity Urine disease, can be used for treating and preventing diabetes.

Description of the drawings

Fig. 1 is fasting blood sugar level；

Fig. 2 is blood sugar level curve after insulin injection；

Fig. 3 is blood sugar level quantitative analysis results (area under curve AUC) after insulin injection；

Fig. 4 is blood sugar level curve after oral glucose；

Fig. 5 is blood sugar level quantitative analysis results (area under curve AUC) after oral glucose.

Specific embodiment

Technical scheme is specifically introduced with reference to the accompanying drawings and examples.

Experimental technique：

1st, the foundation of animal model

Take C57BL/6 male mice 60, body weight 18-20g, 6 week old.After mice adapts to one week, random packet is：Normally Feedstuff group (Normal chow diet, NCD), high fat diet group (High fat diet, HFD), 3,5,6,7,8,3', 4'- seven Methoxy flavone low dose group (HMF-L) and 3,5,6,7,8,3', 4'- Heptamethoxyflavone high dose group (HMF-H), except normal Feedstuff group other groups outer are all using high fat diet.HFD feed formula is：1.25% cholesterol, 20% Adeps Sus domestica, 5% sucrose, 0.5% cholic acid, vitamin are adjusted to normal level.Modeling starts administration, and experimental period is that 6 weeks, NCD and HFD gave same volume 0.5%CMC-Na solution.

2nd, dosage and administering mode：In HFD Induction experiments, mice is carried out using the administering mode of gavage.Modeling is opened Begin to be administered, NCD and HFD gives the 0.5%CMC-Na solution of same volume, be administered six weeks altogether.HMF-L group dosage is 25mg/ G/d, HMF-H group dosage is 50mg/g/d.HMF becomes suspension with 0.5CMC-Na solution allocation.

3rd, blood sugar detection：In corresponding time point, Mouse Tail-tip blood, entered using Omron and Omron blood sugar test paper Row blood-sugar level measuring.

Experimental result：

Fasting blood sugar level higher than one of diabetes diagnostic criterion that 7.0mM is that World Health Organization specifies, as shown in figure 1, making After mould, the blood glucose of high fat group is up to 8.55mM, and Glycemia Decline success is described, HMF-L group and HMF-H group after administration, and blood glucose is respectively 7.12 and 6.99mM are down to, with statistical discrepancy (P ＜ 0.05) compared with HFD.Insulin resistant is the main of type ii diabetes Feature, i.e. impaired glucose tolerance, insulin sensitivity reduces, in order to further confirm that HMF, to diabetes improvement result, carried out respectively Insulin tolerance (Insulin tolerance test, ITT) and oral glucose tolerance (Oral glucose tolerance Test, OGTT), and area under its corresponding curve line (Area under the curve, AUC) is measured.

After being administered 4 weeks, insulin resistant measure is carried out, after mice fasting 6h, gives mouse peritoneal injection insulin 0.75IU/kg, lumbar injection 0,30,60,90,120,150min, tail point blood sampling determines mouse blood sugar, and calculates below ITT line Product.Insulin tolerance test be reflection experiment of the body to insulin sensitivity, type ii diabetes be mainly characterized by insulin Opposing, reduces to insulin sensitivity, i.e., in injection same insulin same time, blood glucose is higher than normal body, as shown in Fig. 2 After giving identical insulin, HFD group blood glucose decrease speed substantially slows down, 30,60,90,120,150min fasting blood sugar level Normal group is significantly higher than, and obvious insulin resistant is occurred in that after pointing out HFD modeling, has effectively reversed this different after HMF administration Chang Xianxiang, AUC result shows, the reverse effect of HMF-H is notable (P ＜ 0.05).Result above shows HMF energy effectively treatment with pancreas The type ii diabetes that island opposing is characterized.For being further characterized by this result, we adopt GraphPad Prism computed in software Under response curve line, area (AUC) is used for quantitative analyses, as shown in figure 3, the AUC of HFD group ITT is about increased to NCD's after modeling Twice, after modeling, insulin sensitivity is significantly reduced, and HMF-H compares HFD group and significantly reduces, and with significant difference (P ＜ 0.05) sensitivity of islets of langerhans is significantly improved after, illustrating intervention is administered.

After being administered 5 weeks, glucose tolerance measure is carried out.Carbohydrate tolerance test is a kind of test of oral glucose load, in order to Body being understood to the blood sugar regulation ability after glucose load, is the goldstandard of the diagnosis diabetes that generally acknowledges at present.Resistance to by sugar Amount test, is conducive to the early discovery of abnormal carbohydrate metabolism.When increasing in blood glucose but not yet reaching diabetes diagnostic criterion, it is clear and definite Whether suffer from diabetes, Differential Diagnosiss can be carried out using OGTT.Under normal circumstances, body has a set of mechanism for maintaining blood glucose, mouth Glucose is taken, after the of short duration rising of blood glucose, rapid recovery is normal, i.e. normal glucose tolerance, area under corresponding oral glucose tolerance curve line Less, the Use barriers of diabeticss sugar, after oral glucose, blood glucose is raised rapidly, and blood glucose decrease speed is slower, i.e., sugared resistance to Measure area under the corresponding line that goes down larger, impaired glucose tolerance in the experiment.As shown in figure 4, the mice for giving overnight fasting is identical After the glucose of equivalent, HFD group fasting blood sugar level is above normal group in 15,30,60,90,120min, goes out after showing modeling Show obvious sugar tolerance to go down, HMF-L and HMF-H intervention has effectively reversed this result, in order to better illustrate this Phenomenon, we are measured to area (AUC) under its corresponding curve line, as a result show, compared with NCD group, the AUC of HFD group Increasing 64%, HMF-L and HMF-H group and this rising (Fig. 5) has been reversed with dose-effect is dependent, illustrates that HMF effectively changes It has been apt to impaired glucose tolerance, that is, has improved the principal character islets of langerhans opposing of type ii diabetes.

In Fig. 1-Fig. 5, the meaning of symbology is：Compare with NCD, * P ＜ 0.05, * * P ＜ 0.01, * * * P ＜ 0.001； Compare with HFD, there was no significant difference for n.s., * P ＜ 0.05, * * P ＜ 0.01, * * * P ＜ 0.001.

In sum, HMF can be effectively improved the fasting blood sugar level rising of the diabetes model of high fat diet induction, change The kind type ii diabetes for being reduced to principal character with impaired glucose tolerance and insulin sensitivity.

Also find in experiment, Radix Polygalae mouth diphenylene ketone oxide can strengthen HMF prevention and treatment diabetes effect, according to above-mentioned experiment side Method is using HMF and Radix Polygalae mouth diphenylene ketone oxide (dosage is 0.1 times of the HMF dosage) group of a half-value dose in HMF low dose group Close using can just make blood sugar recovery to the level of NCD group, ITT area under curve AUC for 370, OGTT area under curve is 810, all there was no significant difference (P ＞ 0.05) with NCD group.Individually give above-mentioned dosage Radix Polygalae mouth diphenylene ketone oxide when, blood glucose and HFD group There was no significant difference (P ＞ 0.05), ITT and OGTT area under curve AUC is respectively 750,1290.

The effect of above-described embodiment is only that the essentiality content of the explanation present invention, but does not limit the guarantor of the present invention with this Shield scope.It will be understood by those within the art that, technical scheme can be modified or be equal to replace Change, the essence without deviating from technical solution of the present invention and protection domain.

Claims

1. a kind of medicine for preventing or treating diabetes, it is characterised in that：Active component includes polymethoxyflavone.

2. the medicine for preventing or treating diabetes according to claim 1, it is characterised in that：The Polymethoxylated Huang Ketone is 3,5,6,7,8,3', 4'- Heptamethoxyflavone.

3. the medicine for preventing or treating diabetes according to claim 1 and 2, it is characterised in that：The activity becomes Dividing also includes Radix Polygalae mouth diphenylene ketone oxide, is the compositionss of polymethoxyflavone and Radix Polygalae mouth diphenylene ketone oxide.

4. a kind of pharmaceutical preparation for preventing or treating diabetes, it is characterised in that：Arbitrary described including claim 1-3 Active component, also includes pharmaceutically acceptable carrier or excipient, makes pharmaceutically acceptable dosage form.

5. the pharmaceutical preparation for preventing or treating diabetes according to claim 4, it is characterised in that：Described pharmaceutically Acceptable carrier or excipient include one or more solid, semi-solid or Auxiliary Liquid Material.

6. the pharmaceutical preparation for preventing or treating diabetes according to claim 4, it is characterised in that：Described pharmaceutically Acceptable dosage form includes tablet, dispersible tablet, capsule, soft capsule, microcapsule, granule, injection, injectable powder, jelly Dry powder injection, pellet, drop pill, syrup, powder, extractum, soft extract, oral liquid.