CN100586431C - Application of procyanidin B2 in preparing medicine for preventing and treating diabetes and vascular complication - Google Patents
Application of procyanidin B2 in preparing medicine for preventing and treating diabetes and vascular complication Download PDFInfo
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- CN100586431C CN100586431C CN200710061216A CN200710061216A CN100586431C CN 100586431 C CN100586431 C CN 100586431C CN 200710061216 A CN200710061216 A CN 200710061216A CN 200710061216 A CN200710061216 A CN 200710061216A CN 100586431 C CN100586431 C CN 100586431C
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Abstract
The present invention discloses an application of procyanidin B2 in the preparation of the drugs for preventing and treating the diabetes and the vascular complications, the trials prove that the procyanidin B2 can reduce the blood glucose concentration of the rats to a certain extend, more importantly, the present invention can inhibit the non-enzymatic glycation reaction in the bodies of rats with diabetes and reveal that the benefits of the control of the diabetic vascular complications are mainly come from the strong antioxidant capacity and the inhibition of the formation of the non-enzymatic glycation metabolites, at the same time, the present invention also has the effect of reducing the blood lipid of the rats with diabetes and the good synergistic effect for the control of the progress of the diabetic vascular complications, so the present invention is conductive to the prevention and the treatment of metabolic syndrome; a plurality of functions possessed by the procyanidin B2can remarkably enhance the advantages of procyanidin B2 in the prevention and the treatment of diabetic vascular complications, the procyanidin is high- efficient, non-toxic and high in safety, therefore, the present invention has broad application prospect in the clinical prevention and treatment of the diabetic vascular complications.
Description
Technical field
The present invention relates to a kind of procyanidin B 2 and prevent and treat the application of diabetes and vascular complication medicine in preparation.
Background technology
Along with improving constantly of living standards of the people, various what is called " affluenza " are also constantly threatening human health.Diabetes are a kind of representative lifelong diseases wherein.Nearest epidemiological survey confirms that the diabetes prevalence of China has become No. three killer after cardiovascular and cerebrovascular disease and cancer up to 10%.And the harm of diabetes is therefore very urgent to the study on prevention of diabetic vascular complications mainly from diabetic vascular complications.Diabetic individual body internal protein generation nonenzymatic glycosylation causes the nonenzymatic glycosylation metabolite to increase, and is one of major reason that causes diabetic vascular complications.The nonenzymatic glycosylation metabolite increases, can directly promote the blood capillary basement membrane thickened, induced tumor growth factor-beta various kinds of cell factor expressions such as (TGF-β), irritation cell epimatrix hypertrophy, can also produce series reaction by combining, finally cause the generation of diabetic vascular complications with nonenzymatic glycosylation metabolite receptor (RAGE)
[1-2]Autoxidation has important function in a series of cascade reactions that the nonenzymatic glycosylation metabolite forms, oxidative stress strengthens can cause nonenzymatic glycosylation metabolite generation increase.The free radical scavenging base can significantly suppress the formation of nonenzymatic glycosylation metabolite
[3], enhanced oxidative stress can quicken the formation of nonenzymatic glycosylation metabolite during diabetes, and then promotes the development of diabetic vascular complications.Therefore suppress non-enzymatic glycation, suppressing the generation of nonenzymatic glycosylation metabolite is the New Policy of control diabetic vascular complications.
List of references:
1.Brownnlee?Mvlassara?H，Aminoguanidine?prevents?diabetes?induced?arterial?wall?proteincross?linking.Science，1986，232：1629-1728.
2.Saiithlal?G?B，Chrttha?P，Chandrnkasan?G.The?role?of?metal-cat-analyzed?oxidation?in?theformation?of?advanced?glycation?products：in?vitro?study?on?collagen.Free?Radic?Biol?Med.1998，25：265-269.
3.Varvarovska?J，Racek?J，Stozickyky?F，et?al.Paranleters?of?oxidative?stress?in?children?withType?I?diabetes?mellitus?and?their?relatives.J?Diabetes?Complications，2003，17：7-10.
Summary of the invention
The purpose of this invention is to provide a kind of procyanidin B 2 and prevent and treat the application of diabetes and vascular complication medicine in preparation.
Technical scheme of the present invention is summarized as follows:
Procyanidin B 2 is prevented and treated the application of diabetes and vascular complication medicine in preparation.
We observe procyanidin B 2 can to a certain degree reduce the blood sugar concentration of rat, the more important thing is simultaneously and can suppress non-enzymatic glycation in the diabetes rat body, the benefit that discloses its control of diabetes vascular complication is mainly from powerful oxidation resistance and the formation that suppresses the nonenzymatic glycosylation metabolite, it also has the effect that reduces the diabetes rat blood fat simultaneously, progress to the control of diabetes vascular complication also has good synergism, helps to prevent and treat metabolic syndrome.The many-side effect that procyanidin B 2 had makes its advantage aspect the control diabetic vascular complications more obvious.The procyanidin high effect nontoxic, safety is high, therefore has broad application prospects in the clinical prevention diabetic vascular complications.
The specific embodiment
The present invention is further illustrated below in conjunction with specific embodiment.
Embodiment 1
The active testing of procyanidin B 2 blood sugar lowering and inhibition nonenzymatic glycosylation
1. test material: animal: male Wistar rat, Beijing animal center provides.Reagent: procyanidin B 2 (Tianjin spike natural product research and development company limited self-control, purity is 98%); Streptozotocin (STZ), aminoguanidine (AG) are U.S. Sigma company product; Hydroxyethyl piperazine ethanesulfonic acid (HEPES) is a U.S. Sigma company product, the packing of Beijing Jing Ke company; Instrument: DV650 full automatic biochemical apparatus, SHIMAZU 1601 ultraviolet-uisible spectrophotometers, micropipettor, electronic analytical balance, vortex vortex mixer.
2. test method: (1) diabetes animal model preparation: 90 of 180-220g male Wistar rats, adaptability was fed three days, selected 12 rats as the normal control group at random.Surplus left lumbar injection STZ60mg/kg behind 78 rat limosis 12h, all give normal diet after the injection, survey rat limosis tail vein sugar behind the 12h, blood glucose＞16.7mmol/L is diabetes modeling success.Get 60 of modeling winners and include test in, surplus discarding.(2) animal grouping and feeding: diabetes rat is divided into 5 groups at random, blank group, AG treatment group, procyanidin B 2 be low, in and high dose group, 12 every group.The blank group is irritated stomach with tap water, AG treatment group is irritated stomach with the AG of 150mg/kgd, procyanidin B 2 is low, in and high dose group uses 50,100 respectively, the procyanidin B 2 of 150mg/ (kgd) is irritated stomach, irritate stomach 1 at 4 o'clock in afternoon every day, each group all gives the standard feed routine feeding, ad lib and drinking-water do not use insulin.In the nursing process, each organizes rat all natural death, and each group has 12 rats during on-test, and during off-test, each group all has 10 rats.(3) specimen sampling: after feeding for 12 weeks, rat limosis 6h weighs, 2% pentobarbital sodium intraperitoneal anesthesia, and it is standby that the exoculation ball is got blood 5ml.Other cuts open the belly and takes out the two kidneys of rat, and two kidneys are removed peplos and weighed.Getting the part kidney inserts in the liquid nitrogen freezing.(4) detection of nonenzymatic glycosylation end-product (AGEs) in the body in the renal cortex: use fluorescence measurement AGEs.Get renal cortex 0.5g, be cut into small pieces, add normal saline 1ml and wear into homogenate, the centrifugal 10min of 2500r/min abandons supernatant, adds chloroform-methanol (2: 1) 5ml degrease in precipitation, and 4 ℃ of joltings are spent the night.The centrifugal 15min of 4000r/min abandons supernatant, stays precipitation, with 2ml methanol and 0.5ml distilled water flushing precipitation.The centrifugal 7min of 3000r/min repeats to wash 3 times.Fresh configuration 0.1mol/L HEPES buffer: with total amount is the dissolved in distilled water NaCl 9.36g of 225ml, KCl 0.433g, Na
2HPO
42H
2O 0.158g, glucose 1.17g, HEPES 5.85g regulates pH value to 7.05 with 1mol/LNaOH, and the reuse distilled water is settled to 250ml.Deposit seed is suspended in the test tube of the HEPES buffer that contains 2ml, every test tube adds 280uIV Collagen Type VI enzyme, and makes blank collagenase control tube, behind 37 ℃ of isothermal vibration 24h, the centrifugal 15min of 3500r/min, supernatant are by the renal cortex collagen of collagenase digesting.Measure fluorescence intensity with fluorophotometer at excitation wavelength 370nm, emission wavelength 440nm place, its numerical value is proofreaied and correct with blank collagenase.Then with the hydroxyproline content in the chloramine-t method mensuration Digestive system.AGEs content is a unit (AU/mg Hyp) expression with the contained fluorescence intensity of every milligram of hydroxyproline (Hyp).(5) detection of blood glucose: get above-mentioned rat from blood coagulation 2ml, utilize full automatic biochemical apparatus to measure blood glucose.
3. result of the test: (1) organizes respectively that experimental rat form, kidney are heavy, the comparison of body weight and kidney weight/body weight: the performance of polydipsia, polyphagia, polyuria all appears in all one-tenth mould diabetes rats, owing to become thin and polyphagia be the form of the big abdomen of microcephaly gradually, compare with the normal control group, the intensely dark pool of hair color, wound is difficult for healing behind the tail vein blood.Diabetes rat 12 during week the normal matched group of body weight significantly reduce, kidney weight/body weight ratio obviously raises; Kidney weight/body weight ratio the comparison of each dosage group of AG treatment group and B2 the results are shown in Table 2 according to group low (P＜0.01).
Table 2 organizes respectively that rat body weight, kidney are heavy, kidney weight/weight ratio is than (x ± s)
Annotate: variance analysis and t check, compare with the normal control group,
*P＜0.05,
*Compare with the blank group P＜0.01, is P＜0.01.
(2) serum blood glucose and renal cortex AGEs: during off-test, there is significant difference in each test group blood glucose value only B2 high dose group and blank group.The group of AG treatment simultaneously, each dosage group of procyanidin B 2 are compared with normal control group, blank group, kidney of rats cortex AGEs all have significant differences (
*P＜0.01), AG treatment group AGEs be lower than the procyanidin B 2 low dose group (
△P＜0.05), the procyanidin B 2 high dose group be lower than the procyanidin B 2 low dose group (
#P＜0.01), the no significance of comparing between the middle and high dosage group of procyanidin B 2 and with AG treatment group.(seeing Table 3)
Table 3 is respectively organized blood glucose and the renal cortex AGEs measurement result of rat
The result shows: the B2 high dose group has certain effect of lowering blood sugar, and senior middle school's low dose group all can suppress renal cortex simultaneously
The formation of AGEs, thus nonenzymatic glycosylation suppressed, prevent and treat the generation of diabetes blood light syndrome.
Embodiment 2
(1) extract: the 95 ℃ of warm macerating of water normal pressure that add 2000g in the 500g Semen Vitis viniferae extract 5 times, and extraction time was respectively 5,4,3,2,1 hours, filtered, and the order number of filter screen is 120, and extracting solution merges to leave standstill to temperature and is lower than 50 degree, abandons precipitation, supernatant;
(2) macroporous resin adsorption is separated: will (1) middle extracting solution through HP20 type macroporous resin adsorption, water, concentration of volume percent are 10%, 30%, 50%, 70%, 95% ethanol water gradient elution, every 250ml receives volume as one, detect by thin layer chromatography method and binding analysis type HPLC, collect the component that is rich in procyanidin B 2, its merging, in temperature≤60 ℃, vacuum is 0.06～0.08MPa concentrating under reduced pressure, and pol is 40, gets the enriched substance of procyanidin B 2;
(3) polyamide separates: the enriched substance of the procyanidin B 2 that macroporous resin adsorption obtains after separating is dispersed in the water (1: 4) and carries out polyamide and separate, water, concentration of volume percent are 20%, 50%, 70%, 95% ethanol water, by method and binding analysis type HPLC detections such as thin layer chromatographies, the component of procyanidin B 2 is rich in collection, with eluent in temperature≤60 ℃, vacuum is 0.06～0.08MPa concentrating under reduced pressure, pol is 10, gets the enriched substance of procyanidin B 2.The content of procyanidin B 2 is 37.4%.
(4) ODS mesolow column chromatography for separation: the component that will be rich in procyanidin B 2 after will separating by polyamide is carried out ODS mesolow column chromatography, water, percent by volume is 10%, 20%, 30%, 40%, 50% methanol aqueous solution gradient elution, every 50ml receives volume as one, by method and binding analysis type HPLC detections such as thin layer chromatographies, with the pure product of procyanidin B 2 product in contrast, the component of procyanidin B 2 is rich in collection, and with it in temperature≤60 ℃, vacuum is 0.06～0.08MPa concentrating under reduced pressure, pol is 10, and measure with the method for embodiment 1: the content of procyanidin B 2 is 75.3%.(5) Sephadex LH-20 carries out purification: the component that contains procyanidin B 2 that obtains in (4) is carried out the SephadexLH-20 column chromatography purification, methanol with percent by volume 30% carries out eluting, every 10ml receives volume as one, by method and binding analysis type HPLC detections such as thin layer chromatographies, with the pure product of procyanidin B 2 product in contrast, the component of procyanidin B 2 is rich in collection, with eluent in temperature≤60 ℃, vacuum is the 0.06-0.08MPa concentrating under reduced pressure, obtain pol and be 20 component, lyophilization obtains procyanidin B 2 (260mg).
Utilize ESI-MS,
1H-NMR and
13Spectrum means such as C-NMR also contrast in data in literature, have identified the structure of separating the procyanidin B that obtains according to said method.Utilize standard substance (purchase of U.S. CHROMDEX company) to demarcate on this basis, measuring the plain B2 content of procyanidin is 98%.The procyanidin B 2 pale yellow powder, polyamide film launches with n-butyl alcohol-acetic acid-water (4: 1: 3), and Rf is that 0.3,5% ferric chloride alcoholic solution shows single blue spot.Provided quasi-molecular ion peak [M-H] among the anion ESI-MS
-577 and [M-H+Cl]
-612, its
1H-NMR (300MHz, inDMSO) middle signal overlapping is more serious, its
13Signal is clear among the C-NMR (75MHz, in DMSO), contrasts with document and has carried out full ownership, is accredited as procyanidin B 2, the results are shown in following table.
Chemical compound among table 1 the present invention
13The C-NMR data
Raw material in the present embodiment can also select: the root of Pinaceae pine genus plant, bark, leaf; Or the root of rosaceous plant, stem, leaf, fruit, seed; Or the root of Vitaceae Vitis plant, stem, fruit, seed; Or fabaceous stem or to plant skin be raw material.
Claims (1)
1. procyanidin B 2 is as the application of unique active component in preparation control diabetic vascular complications medicine.
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| WO2010089874A1 (en) * | 2009-02-05 | 2010-08-12 | フジッコ株式会社 | Ppar-γ-expression-enhancing agent, adiponectin-production-enhancing agent, ucp-activating agent, and pharmaceutical preparation, food or beverage comprising any one of the agents |
| US20140179774A1 (en) | 2012-12-26 | 2014-06-26 | Industrial Technology Research Institute | Methods for inhibition of shc-1/p66 to combat aging-related diseases |
| CN103494800A (en) * | 2013-10-18 | 2014-01-08 | 武汉大学 | Application of procyanidine B2 in preparation of drugs for preventing oxidative damage and inhibiting cell apoptosis |
| CN106138217B9 (en) * | 2016-08-08 | 2020-08-25 | 陕西君碧莎制药有限公司 | Application of mulberry particles in preparation of medicine for preventing and treating diabetes and complications thereof |
| CN107522684B (en) * | 2017-09-15 | 2020-06-12 | 广西壮族自治区中国科学院广西植物研究所 | Preparation method and application of high-content procyanidine from avocado kernels |
| CN111643494A (en) * | 2020-06-16 | 2020-09-11 | 南通大学 | Application of procyanidine B2 in preparation of medicine for inhibiting pressure load type ventricular remodeling |
| CN114832035A (en) * | 2022-05-09 | 2022-08-02 | 中国科学院西北高原生物研究所 | Rheum officinale petiole procyanidine extract and preparation method and application thereof |
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Non-Patent Citations (6)
| Title |
|---|
| 葡萄籽原花青素抗动脉粥样硬化研究进展. 马亚兵，高海青.山东医药，第42卷第33期. 2002 |
| 葡萄籽原花青素抗动脉粥样硬化研究进展. 马亚兵，高海青.山东医药，第42卷第33期. 2002 * |
| 葡萄籽提取物的质量标准. 邵云东，高文远，苏艳芳，肖培根.中国中药杂志，第30卷第18期. 2005 |
| 葡萄籽提取物的质量标准. 邵云东，高文远，苏艳芳，肖培根.中国中药杂志，第30卷第18期. 2005 * |
| 葡萄籽提取物的质量评定. 冯建光.中国食品添加剂，第2期. 2004 |
| 葡萄籽提取物的质量评定. 冯建光.中国食品添加剂，第2期. 2004 * |
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Denomination of invention: Application of procyanidin B2 in preparing medicine for preventing and treating diabetes and vascular complication Effective date of registration: 20101206 Granted publication date: 20100203 Pledgee: Tianjin TEDA Small Enterprise Credit Guarantee Center Pledgor: Jianfeng Natural Product R&D Development Co., Ltd., Tianjin Registration number: 2010990000991 |
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