Application of taxifolin in preparation of anti-metabolic syndrome medicines
阅读说明：本技术 花旗松素在制备抗代谢综合征类药物中的应用 (Application of taxifolin in preparation of anti-metabolic syndrome medicines ) 是由 郑晓珂 张奇 袁培培 齐曼 傅阳 侯颖 魏亚新 高丽媛 冯卫生 于 2019-11-29 设计创作，主要内容包括：本发明涉及花旗松素在制备抗代谢综合征类药物中的应用,可有效解决抗代谢综合征的用药问题,其解决的技术方案是,本发明首次证实花旗松素可以治疗MS,可以作为花旗松素被开发为治疗MS类药物的有力论据,开辟了花旗松素的新用途,具有良好的推广和应用价值。(The invention relates to application of taxifolin in preparation of anti-metabolic syndrome medicines, which can effectively solve the problem of medication of anti-metabolic syndrome.)
1. Application of taxifolin in preparing medicines for resisting metabolic syndrome is provided.
2. The taxifolin of claim 1, wherein the taxifolin has the formula C15H12O7Structural formula is
3. The taxifolin according to claim 2, wherein 16.5kg of spina gleditsiae is subjected to tissue disruption extraction with 50% acetone aqueous solution for 3 times, concentrated to obtain 1.6kg of total extract, the total extract is suspended with 6L of water, extracted with petroleum ether, ethyl acetate, n-butanol and water to obtain 15.1g of petroleum ether extraction part, 300.9g of ethyl acetate extraction part, 150.5g of n-butanol extraction part and 992.8g of water part, the ethyl acetate part of spina gleditsiae is subjected to sample concoction with column chromatography silica gel at a ratio of 1:1, the column is packed by a dry method, gradient elution with dichloromethane-methanol is adopted, and then TLC is used for identification, and the same components are combined to obtain A1-A8Total eight fractions, convection fraction A8And repeatedly performing silica Gel, Toyopearl HW-40C, Sephadex LH-20, MCL Gel CHP-20 and ODS column chromatography, recrystallization, thin layer preparation and liquid phase preparation for separation and purification to obtain 16.4g of taxifolin.
Technical Field
The invention relates to the field of medicines, in particular to application of taxifolin in preparation of anti-metabolic syndrome medicines.
Background
The Metabolic Syndrome (MS) is a group of complex metabolic disorder syndromes accompanied with metabolic disorders of substances such as body protein, fat, sugar and the like, the clinical manifestations comprise abdominal obesity or overweight, abnormal lipid metabolism, hypertension, hyperglycemia, insulin resistance, hyperinsulinemia and the like, the MS is an important cause of various cardiovascular diseases such as myocardial hypertrophy, coronary heart disease, atherosclerosis, myocardial infarction and the like, and the finding of effective active compounds for preventing and treating the metabolic syndrome is the responsibility of contemporary researchers.
Spina Gleditsiae is a dry spina Gleditsiae (Gleditsia sinensis Lam.) of Gleditsia. 2015, recorded in pharmacopoeia of the people's republic of China, spina Gleditsiae has effects of relieving swelling, removing toxic substance, expelling pus, and killing parasite. The Chinese honeylocust spine is mainly used for treating thrombus, stroke, scabies, ulcer, eczema, endocrine and various cancers (nasopharyngeal carcinoma, ovarian cancer, prostatic cancer and the like) and the like in clinic. The experiment shows that the flavonoid taxifolin extracted from the spina gleditsiae has pharmacological activity of resisting MS for the first time. (Replacing into spina Gleditsiae content)
The taxifolin is also named as dihydroquercetin or folium Alstoniae Scholaris, and has molecular formula of C15H12O7The taxifolin has molecular weight of 304.25, is a natural flavonoid compound existing in spina gleditsiae, can be used for treating MS for the first time, and can be used as a strong argument for developing MS medicines.
Disclosure of Invention
In view of the above situation, in order to solve the defects of the prior art, the present invention aims to provide an application of taxifolin in the preparation of anti-metabolic syndrome drugs, which can effectively solve the problem of anti-metabolic syndrome drug use.
The technical scheme of the invention is that the taxifolin has a molecular formula of C15H12O7Structural formula is
The invention proves that the taxifolin can treat MS for the first time, can be used as a powerful argument for the taxifolin to be developed into MS medicines, opens up a new application of the taxifolin, and has good popularization and application values.
Drawings
FIG. 1 is a structural formula of taxifolin of the present invention.
FIG. 2 shows the nuclear magnetic resonance of taxifolin of the present invention13C-NMR spectrum.
FIG. 3 shows the nuclear magnetic resonance of taxifolin of the present invention1HNMR atlas.
Detailed Description
The following describes in detail embodiments of the present invention in conjunction with the actual situation.
In the specific implementation of the invention, the method for extracting the taxifolin comprises the steps of carrying out tissue crushing and extraction on 16.5kg of spina gleditsiae by 50% acetone aqueous solution for 3 times, concentrating to obtain 1.6kg of total extract, adding 6L of water into the total extract for suspension, extracting by adopting petroleum ether, ethyl acetate, n-butanol and water to obtain 15.1g of petroleum ether extraction part, 300.9g of ethyl acetate extraction part, 150.5g of n-butanol extraction part and 992.8g of water part, and carrying out sample concomitation on the ethyl acetate part of the spina gleditsiae and column chromatography silica gel (100-mesh 200-mesh) at a ratio of 1:1Loading on column by dry method, gradient eluting with dichloromethane-methanol (100:0 to 0:100), detecting by TLC, and mixing the same components to obtain A1-A8Total eight fractions, convection fraction A8The obtained product was subjected to silica Gel, Toyopearl HW-40C, Sephadex LH-20 (hydroxypropyl dextran Gel), MCL Gel CHP-20, ODS (octadecylsilane) column chromatography, recrystallization, thin layer preparation, and liquid phase separation repeatedly to obtain 16.4g of taxifolin.
The above method can be repeated for several times, and the same or similar result can be obtained, and 0.99g of taxifolin can be obtained per 1kg of spina Gleditsiae.
The extract of the invention is prepared by13C-NMR and1HNMR determination, its map is shown in fig. 2 and fig. 3, its molecular structural formula is shown in fig. 1, and its molecular formula is C15H12O7The molecular weight is 304.25, the taxifolin is identified as taxifolin, MS can be treated through experiments, the taxifolin can be used as a strong argument for the taxifolin to be developed into MS medicines, a new application of the taxifolin is developed, the application of the taxifolin in the preparation of MS medicines is realized, and relevant experimental data are as follows:
1 materials of the experiment
1.1 Experimental animals and cells
The experimental animals are selected from 13 male Wistar Kyoto Rats (WKY) and 36 Spontaneous Hypertension Rats (SHR) with seven weeks of age, purchased from Beijing Wintolite laboratory animal technology Limited company, license number: SCXK (Kyoto) 2016-.
1.2 reagents and instruments
Taxifolin (B20539, source leaf organism, China); fructose (EC06BA0005, Diamond, China); valsartan (national drug standard H20050508, henna royal pharmaceutical products limited, China); total cholesterol test kit (TG; A111-1, Nanjing institute of bioengineering, China); triglyceride test kit (T-CHO; A110-1-1, Nanjing institute of bioengineering, China); low density lipoprotein cholesterol test kit (LDL-C; A113-1, Nanjing institute of bioengineering, China); high density lipoprotein cholesterol test kit (HDL-C; A112-1, Nanjing institute of bioengineering, China); a non-invasive tail artery sphygmomanometer (Techman, China); one-ten-thousandth precision analytical balance type AB204-N (Mettler Toledo, Sweden); an iMARK type microplate reader (Bio-Rad, USA); Centrifuge-5804R small high-speed cryogenic Centrifuge (Eppendorf, Germany); ultrapure water (611VF Sartorius, Gottingen, Germany); 0.9% aqueous sodium chloride solution (homa, korn pharmaceuticals, inc., hana, hannan); ultra low temperature refrigerator (hai group, China) at-80 ℃; a low temperature refrigerator (Mike Mitsubishi group, China) at-20 ℃.
2 method of experiment
2.1 in vivo experiments
2.1.1 grouping and administration
The experiment was divided into five groups, with WKY as a normal control group, given free drinking of distilled water, and with 1mL/100g intragastric administration of distilled water per day. Free drinking induction given 10% fructose solution to all SHRs established a model of MS rats and divided them into four groups on the weight and blood pressure balance principle: model group SHR (F), and normal group perfuse distilled water with equal dosage; the taxifolin low dose group SHR (F) + TA-L, 25mg/kg taxifolin is administered by gavage; the flag pinocembrin high dose group SHR (F) + TA-H, 50mg/kg flag pinocembrin is administered by intragastric administration; the positive drug group SHR (F) + Y, 30mg/kg valsartan is administered by intragastric administration.
2.1.2 detection of Mould index, body weight and Lee' index
Rat Systolic Blood Pressure (SBP) is detected by a noninvasive tail artery blood pressure meter, and training is started during adaptive culture so that rats adapt to a measurement environment. Drug dry prognosis was initiated and tested once a week. Blood is collected by orbital venous blood sampling method every two weeks, fasting blood glucose value is detected by a glucometer, and then the blood serum is obtained by centrifugation for 20min at 4 ℃ and 3000g, and fasting insulin content is detected by radioactive immunity. Taking the influence result of taxifolin on SBP and HOMA-IR as an index, taking materials in the seventh week of the experiment, weighing and recording the weight and the body length (the linear distance from the tip of the nose to the anus) of the rat before taking materials.
Insulin resistance index (HOMA-IR) ═ fasting blood glucose level x fasting insulin content/22.5
Lee's index ═ body weight (g). times.1000 ^ (1/3)/body length (cm)
2.1.3 detection of Biochemical indicators
The abdominal aorta of a rat is subjected to blood sampling, after the blood is stood at room temperature, the blood is centrifuged for 20min at 3000 revolutions, and the supernatant is taken to obtain serum, and the contents of TG, T-CHO, LDL-C and HDL-C in the serum are detected. All detection steps followed strictly the kit instructions.
2.1.4 statistical analysis
Data were analyzed for One-Way analysis of variance (One-Way ANOVA) using SPSS 18.0 software for comparison between groups. The experimental data are as followsAnd (4) showing. P<0.05 indicates that the difference is significant, P<0.01 indicates that the difference is very significant.
3 results of the experiment
3.1 Effect of taxifolin on basic index of MS rats
Compared with the WKY group, the rats in the SHR (F) group have obviously increased SBP, HOMA-IR, TG, T-CHO and LDL-C levels, body weight and Lee's index and obviously reduced HDL-C level (P <0.01), which indicates that the rats in the SHR (F) group have pathological states of hypertension, insulin resistance and lipid metabolism disorder, are obese in body and have already developed MS, but the taxifolin can obviously (P <0.05 or P <0.01) improve the indexes and relieve the basic pathological manifestations of the MS rats. See tables 1-2.
TABLE 1 Effect of farnesoid on SBP, HOMA-IR, body weight and Lee's index in MS rats
Note: the numerical value is expressed as
TABLE 2 Effect of taxifolin on four indicators of lipid metabolism in MS rats
Note:the numerical value is expressed as
4. Conclusion
Fructose feeding SHR is a very stable and commonly used method currently used to establish a rat model of MS. Clinical manifestations of MS include abdominal obesity or overweight, abnormal lipid metabolism, hypertension, hyperglycemia, Insulin Resistance (IR), hyperinsulinemia, and the like. The experiment is carried out by detecting the SBP reaction hypertension state of the rat; detecting the HOMA-IR response insulin resistance state; detecting the reaction lipid metabolism state of TG, T-CHO, LDL-C and HDL-C; rat body weight and Lee's index response whether rats were obese were weighed and calculated. The result proves that the taxifolin can comprehensively improve various metabolic disorder pathological states in the MS rat body.
Through the experiments, the invention firstly proves that the taxifolin can treat MS, prompts that the taxifolin has the potential of being developed into MS medicines, opens up the new application of the taxifolin, has good popularization and application values and has obvious economic and social benefits.
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