CN101502529B - Application of vincetoxicoside B in preparing antidiabetic medicament - Google Patents
Application of vincetoxicoside B in preparing antidiabetic medicament Download PDFInfo
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- CN101502529B CN101502529B CN2009100376466A CN200910037646A CN101502529B CN 101502529 B CN101502529 B CN 101502529B CN 2009100376466 A CN2009100376466 A CN 2009100376466A CN 200910037646 A CN200910037646 A CN 200910037646A CN 101502529 B CN101502529 B CN 101502529B
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- 239000003814 drug Substances 0.000 title claims abstract description 22
- 239000003472 antidiabetic agent Substances 0.000 title claims abstract description 14
- 230000003178 anti-diabetic effect Effects 0.000 title claims abstract description 13
- QPHXPNUXTNHJOF-XNFUJFQVSA-N quercetin 7-O-alpha-L-rhamnopyranoside Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC1=CC(O)=C2C(=O)C(O)=C(C=3C=C(O)C(O)=CC=3)OC2=C1 QPHXPNUXTNHJOF-XNFUJFQVSA-N 0.000 title abstract description 4
- QPHXPNUXTNHJOF-UHFFFAOYSA-N quercetin-7-O-beta-L-rhamnopyranoside Natural products OC1C(O)C(O)C(C)OC1OC1=CC(O)=C2C(=O)C(O)=C(C=3C=C(O)C(O)=CC=3)OC2=C1 QPHXPNUXTNHJOF-UHFFFAOYSA-N 0.000 title abstract description 4
- BOCRVBHCAQGQNQ-UHFFFAOYSA-N glaucoside-B Natural products O1C(C)C(O)C(OC)CC1OC1C(OC)CC(OC2C(CC(OC2C)OC2C(CC3(C)C4C(C(OC5COC6(C)OC=C(C56)CC4)=O)CC=C3C2)O)OC)OC1C BOCRVBHCAQGQNQ-UHFFFAOYSA-N 0.000 claims description 42
- 238000002347 injection Methods 0.000 claims description 5
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- 239000002775 capsule Substances 0.000 claims description 2
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- 239000003826 tablet Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 7
- 238000011161 development Methods 0.000 abstract description 2
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- 229940127003 anti-diabetic drug Drugs 0.000 abstract 3
- 239000008280 blood Substances 0.000 description 23
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- 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 15
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 15
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- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 11
- 206010012601 diabetes mellitus Diseases 0.000 description 10
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 10
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 229960001052 streptozocin Drugs 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 6
- 102000004877 Insulin Human genes 0.000 description 5
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- 238000002474 experimental method Methods 0.000 description 5
- 229940125396 insulin Drugs 0.000 description 5
- 210000004153 islets of langerhan Anatomy 0.000 description 5
- 230000002218 hypoglycaemic effect Effects 0.000 description 4
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- 210000002784 stomach Anatomy 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000008267 milk Substances 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
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- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical group C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the application of vincetoxicoside B in the preparation of anti-diabetic drugs. The invention provides a novel choice and idea for the existing anti-diabetic drugs, widens the selecting field of the anti-diabetic drugs and contributes to the development of the technical field; the applied vincetoxicoside B of the invention is proved to have remarkable anti-diabetic effect; and the invention is selected from the extract of natural drugs having specific chemical structure, therefore, the feeding is quantifiable in the preparation and the invention is applicable to the preparation of drugs in modern forms.
Description
Technical field
The present invention relates to a kind of new purposes of glaucoside B, the application of glaucoside B in the preparation antidiabetic medicine specifically.
Background technology
Diabetes (diabetes mellitus) are one of current modal chronic diseases, type 2 diabetes mellitus (Type II diabetes mellitus wherein, be non-insulin-dependent diabetes mellitus again, non-insulin-dependentdiabetes mellitus NIDDM) accounts for more than 90% of diabetics.Diabetes all are serious day by day problems in developed country and developing country, and it has caused serious and costly consequence, comprise blind, heart disease and nephropathy etc.According to estimates, from 2000 to the year two thousand fifty, the number of whole world diabetics will increase by 165%.According to the statistics of IDF, at present in state-owned 4.3% population suffer from diabetes, patient's number will break through 5,000 ten thousand in following 20 years.Diabetes are second killers in the modern disease, it is only second to cancer to the harm of human body, human beings'health in serious threat, and present diabetes have the extension and the tendency of rejuvenation, and how preventing and treating diabetes has become the big problem that present the world of medicine pays close attention to.
At present, the pathogenesis that generally believes diabetes mainly contains two kinds: the hypoinsulinism that (1) causes because of beta Cell of islet death or hypofunction; (2) insulin resistant, be meant that insulin carries out the effect deficiency of its normal biological agent, especially muscle, fatty tissue promptly to insulin insensitivity, thereby can not absorb unnecessary glucose in the body fluid to the obstacle that utilizes of glucose efficiently to show as peripheral tissues.Most patients can be passed through Drug therapy, adds to keep on a diet and adhere to that moderate exercise keeps the stable of blood sugar level.The hypoglycemic medicine of promoting the use of on the market at present, its mechanism of action is main: (1) stimulates the pancreatic excreting insulin; (2) reduce intestinal to glucose absorption; (3) suppressing glycogen produces; (4) strengthen peripheral tissue to insulin sensitivity.
Still do not report that at present glaucoside B has hypoglycemic activity.
Summary of the invention
The objective of the invention is provides a kind of new way for the technical field of existing preparation antidiabetic medicine, and glaucoside B is provided the application in the preparation antidiabetic medicine.
(Vincetoxicoside B, Quercetin-7-β-D-rhamnose) are quercetin derivative to glaucoside B, and the molecular formula of glaucoside B is: C
21H
20O
11, structural formula is suc as formula I:
Technical scheme of the present invention is:
The application of glaucoside B specifically is to be applied to prepare antidiabetic medicine.
Described antidiabetic medicine can be prepared into present man-rated pharmaceutical preparation, as tablet, capsule, granule, injection etc.
The invention has the beneficial effects as follows:
1) the present invention has widened the selection field of antidiabetic medicine for present antidiabetic medicine provides a kind of brand-new selection and thinking, also contributes for the development of this technical field; 2) application of glaucoside B of the present invention has been proved to be significant anti-diabetic effect; What 3) the present invention selected for use is the extract of natural drug, is the natural drug with clear and definite chemical constitution, can quantize when being used for pharmacy to feed intake, and is used in the preparation modern formulation.
The most important thing is: the present invention is to the experimentize blood sugar lowering experiment of animal of glaucoside B, at the lasting stomach fat milk of irritating rat is produced on the basis of insulin resistant, use low dose of streptozotocin damage beta Cell of islet, cause rat blood sugar to raise, institute makes animal model and type 2 diabetes mellitus is similar.After experimental type 2 diabetes mellitus rat gives glaucoside B treatment, glaucoside B height, in and the blood glucose value of low dose group and model group blood glucose value relatively, significant difference (P＜0.01) is all arranged, glaucoside B height, in and the blood glucose value before and after the low dose group administration relatively, also have significant difference (P＜0.01), illustrate that glaucoside B has good hypoglycemic activity to experimental type 2 diabetes mellitus.
Simultaneously, the present invention has also investigated glaucoside B causes the beta Cell of islet apoptosis to streptozotocin protective effect.Experiment showed, that glaucoside B can promote normal N IT beta Cell of islet propagation, behind the glaucoside B of maximum concentration (100uM) effect 24h, the activity of NIT beta Cell of islet is compared with normal group, has improved about 30%.And the NIT beta Cell of islet apoptosis that the streptozotocin of 8mM causes is had significant protective effect, the cytoactive of administration group be greatly improved (P＜0.01) of comparing with model group, and dose-effect relationship is obvious.
The specific embodiment
Below further specify technical scheme of the present invention by specific embodiment.
Embodiment 1
Glaucoside B is to the influence of experimental type 2 diabetes mellitus rat
The grouping of 1 animal
Healthy Wistar rat (SPF level), male, body weight 180-220g (providing) by Nanfang Medical Univ's Experimental Animal Center, the feed of freely drinking water, be divided into normal control group and modeling group at random, the modeling group is set up model as follows, the model group animal is divided at random high, normal, basic group of model control group, positive drug gliclazide group, glaucoside B after the modeling success, 1 week of according to the form below successive administration again.
Administration time and dosage see Table 1:
The grouping of table 1 glaucoside B effect experiment animal
The preparation of 2 rat models
Normal rats is irritated the stomach distilled water every day, and high fat group rat is irritated stomach self-control fat milk (1ml/100gBW) every day sooner or later.After 2 weeks of continuous irrigation stomach fat milk, water 24h is can't help in the animal fasting, 10 tail vein injection salines of blank group, the equal tail vein injection 30mg/kgBW of all the other rats streptozotocin (below be abbreviated as STZ) solution (face and use preceding preparation).Behind the administration 48h, water 12h is can't help in fasting, gets blood every 3 hours eyeball rear vein beards, according to blood sugar detection test kit time-and-motion study fasting blood sugar, and METHOD FOR CONTINUOUS DETERMINATION 3 times, fasting blood sugar 〉=16.7mmol/L's is modeling success rat.
The mensuration of 3 blood glucose
After the last administration, water 12h is can't help in the animal fasting, and the eyeball rear vein beard is got blood, measures blood glucose value respectively according to the method for test kit.Adopt the SPSS13.0 statistical software, analyze and respectively organize the situation of change of blood glucose value.
4 glaucoside B are to the influence of experimental type 2 diabetes mellitus rat blood sugar
Experimental result sees Table 2, and as known from Table 2, behind the injection STZ, rat blood sugar rises, and fasting blood sugar 〉=16.7mmol/L behind the 72h illustrates the diabetes model success.After the administration, the positive drug group, glaucoside B height, in and the blood glucose value of low dose group and model group blood glucose value relatively, significant difference (P＜0.01) is all arranged.
Each is organized before the administration, and the T check of blood glucose shows behind the blood glucose and administration, the positive drug group, glaucoside B height, in and the blood glucose value before and after the low dose group administration relatively, have significant difference (P＜0.01).Above result shows that glaucoside B can reduce the blood glucose of experimental type 2 diabetes mellitus rat.
Table 2 experimental result
*P＜0.05vs model group
*P＜0.01vs model group
△P＜0.05vs is on the same group before the administration
△ △P＜0.01vs is on the same group before the administration
Embodiment 2
Glaucoside B causes the protective effect of beta Cell of islet apoptosis to streptozotocin
1 experimental technique
Streptozotocin is the classical diabetes medicament that causes, and there is the nitroso-group group in it, can produce beta Cell of islet toxicant NO.NO participates in many free radical tandem type reactions, induces the beta Cell of islet apoptosis, reduces cellular metabolism and insulin secretion.NIT-1 is a kind of beta Cell of islet that is based upon on the non-fat transgenic mice, is widely used in the hypoglycemic medicine screening.This experiment acts on the NIT-L1 beta Cell of islet with streptozotocin, can draw the damage of NIT-L1 beta Cell of islet, and its pathological changes mechanism is similar to type i diabetes.
Getting well-grown logarithmic (log) phase NIT-L1 beta Cell of islet is inoculated in 96 orifice plates, after 24h is adherent, be divided into 10 groups, blank group, glaucoside B (3uM), glaucoside B (10uM), glaucoside B (30uM), glaucoside B (100uM), model control group (STZ8mM), and glaucoside B (3uM)+STZ, glaucoside B (10uM)+STZ, glaucoside B (30uM)+STZ, glaucoside B (100uM)+STZ, behind the drug effect 24h, measure the NIT-L1 cell activity with mtt assay:
Every hole adds MTT solution 20 μ l, continues to cultivate 4h, abandons supernatant, and every hole adds DMSO150 μ 1, and vibration 10min detects each hole absorbance with microplate reader 492nm wavelength.
2 experimental results
Experimental result sees Table 3 and table 4:
Table 3 variable concentrations glaucoside B is to the influence-1 (n=8) of normal NIT-L1 islet cells growth
*The blank group of P＜0.05vs,
*The blank group of P＜0.01vs,
* *The blank group of P＜0.001vs
Table 4 variable concentrations glaucoside B is to the influence-1 (n=8) of STZ damage NIT-L1 islet cells growth
*P＜0.05vs normal group,
*P＜0.01vs normal group,
* *P＜0.001vs normal group
△P＜0.05vs model group,
△ △P＜0.01vs model group,
△ △ △P＜0.001vs model group
Experimental result shows that glaucoside B can significantly improve the cytoactive (table 3) of normal NIT-L1 beta Cell of islet, and growth has facilitation to islet cells to show glaucoside B, and dose-effect relationship is obvious.Behind the glaucoside B of maximum concentration (100uM) effect 24h, the activity of islet cells is compared with normal group, has improved about 30%.
Utilize concentration to induce NIT-L1 beta Cell of islet apoptosis for the streptozotocin STZ of 8mM, the glaucoside B that observes variable concentrations again causes the protective effect of islet cells damage to STZ.Discovery after glaucoside B effect 24, the cytoactive of administration group be greatly improved (table 4) of comparing with model group, and dose-effect relationship is obvious.
Claims (2)
1. glaucoside B is as the application of unique active component in the preparation antidiabetic medicine; The dosage of described glaucoside B is 1.5mg/kgBW.
2. application as claimed in claim 1 is characterized in that described antidiabetic medicine is tablet, capsule, granule or injection.
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| CN2009100376466A CN101502529B (en) | 2009-03-06 | 2009-03-06 | Application of vincetoxicoside B in preparing antidiabetic medicament |
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| CN1899340A (en) * | 2006-07-12 | 2007-01-24 | 中国人民解放军第二军医大学 | Beggarticks extract and its use |
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