V. I. Toporkova, E. V. Vishnyakov, K. O. Sidorov, I. I. Terninko, D. Ivkin
{"title":"Assessment of the influence of the mineral complex of rutin on the degree of expression of anti-diabetic activity","authors":"V. I. Toporkova, E. V. Vishnyakov, K. O. Sidorov, I. I. Terninko, D. Ivkin","doi":"10.33380/2305-2066-2021-10-4(1)-197-205","DOIUrl":null,"url":null,"abstract":"Introduction. Type 2 diabetes mellitus is currently considered one of the most common non-communicable diseases. For the prevention and concomitant treatment of this pathology, various herbal remedies are successfully used, such as, for example, blueberry shoots. The plant contains phenolic compounds (anthocyanins, flavonoids, phenolcarboxylic and organic acids), which have antioxidant and hypoglycemic effects, and also accumulates macro- and microelements (Ca, Mg, Zn, Mn), which in turn can affect the course of diabetes mellitus. Complexes of elements with phenolic biological active substances (BAS) can affect the formation of a pharmacological response or change its severity. Therefore, it is possible to put forward a hypothesis about the potentiation of the antidiabetic action of phenolic compounds when they exist in the form of mineral complexes.Aim. To carry out a comparative assessment of the antidiabetic activity of the mineral complex rutin with zinc in comparison with precursor substances and extraction from blueberry shoots to predict the effect of elements on the course of this pathology.Materials and methods. The objects of the study were an aqueous solution (C = 0.18 mg/ml) of a model complex of rutin with zinc with a molar ratio of components of 1 : 1 and blueberry shoots purchased from a pharmacy in St. Petersburg. According to the information on the packaging, the region of raw material procurement is Altai Territory, Barnaul, the period for harvesting blueberries is July 2020. The complex of rutin with zinc was obtained according to the method described in the literature from the pharmaceutical substance rutin (Rutin, batch 332, valid until 26.03.2023, Sichuan Guangsong Pharmaceutical Co., Ltd., China, FS 000569-060514) and an aqueous solution (С = 0.13 mg/ml) zinc chloride (Zinc chloride, batch 39/G 4, valid until 09.10.2021, Neva Reaktiv, Russia, STP TU COMP 1-533-2012). The optimal ratio of components 1 : 1 for the formation of a mineral complex was established by us earlier experimentally using the Job's method. The mass of zinc chloride, which must be added to the extraction, and the mass of the complex for the preparation of its aqueous solution were calculated on the basis of the quantitative content of biologically active substances in blueberry shoots and the molar ratio of the components involved in the formation of the complex compound determined by the spectral method. The quantitative content of the main groups of biologically active substances (flavonoids, hydroxycinnamic acids, organic acids) was determined spectrophotometrically on SF-2000 instrument (Russia) and titrimetrically using the methods presented in Russian Pharmacopoeia XIV FS.2.5.0093.18 and FS.2.5.0012.15. The antidiabetic effect of the complex of rutin with zinc was evaluated in comparison with an aqueous extract from the shoots of common blueberries (the ratio of raw materials: extractant – 1 : 80), an aqueous solution of zinc chloride (concentration – 0.36 mg/ml) and their mixture (ratio 1 : 1) on a model of dexamethasone-induced type 2 diabetes mellitus in laboratory animals. Determination of blood glucose concentration was carried out using a portable glucometer \"AccuChek Active\" (Roche Diabetes Care, Germany). The presence of glucosuria and ketonuria was established using Ketoglyuk-1 test strips (Biosensor AN, Russia). Statistical processing of the results was carried out using the Microsoft Excel program according to OFS.1.1.0013.15.Results and discussion. The results of the content of glucose and ketones in urine showed that in the process of modeling diabetes mellitus, glucosuria and ketonuria are characteristic for all groups of animals, which confirmed the formation of a pathological process in rats. A lower content of glucose and ketones in urine was found in a group of animals that received a complex of rutin with zinc (glucose concentration – less than 2.3 mmol/l, ketone concentration – less than 0.2 mmol/l). Measurement of the concentration of glucose in the blood showed that the complex of rutin with zinc has the most pronounced hypoglycemic effect, while the water extract from blueberry shoots and an aqueous solution of zinc chloride have a minimal antidiabetic effect (blood glucose is 6.9 mmol/l versus 8,1 mmol/l and 7.9 mmol/l, respectively).Conclusion. The study of the influence of elements in the composition of phenolic complexes on the course of diabetes mellitus showed that the introduction of minerals has a positive effect on the severity of the pharmacological effect, which can serve as confirmation of the hypothesis about the potentiation of the antidiabetic effect of phenolic compounds when they exist in the form of mineral complexes. Thus, the complex of rutin with zinc showed the maximum activity in comparison with the solution of zinc chloride, extraction from blueberry shoots and their mixture, which suggests that the form of existence of natural phenolic compounds in the composition of mineral complexes is optimal both from the point of view of accumulation and from the side manifestations of a pharmacological response. The results of the study create the preconditions for further study of the effect of various elements in combination with marker phenolic components of antidiabetic herbal preparations on the course of diabetes mellitus, and also make it possible to conclude that natural mineral complexes have a prophylactic effect against this pathology.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2021-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Development and Registration","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-197-205","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction. Type 2 diabetes mellitus is currently considered one of the most common non-communicable diseases. For the prevention and concomitant treatment of this pathology, various herbal remedies are successfully used, such as, for example, blueberry shoots. The plant contains phenolic compounds (anthocyanins, flavonoids, phenolcarboxylic and organic acids), which have antioxidant and hypoglycemic effects, and also accumulates macro- and microelements (Ca, Mg, Zn, Mn), which in turn can affect the course of diabetes mellitus. Complexes of elements with phenolic biological active substances (BAS) can affect the formation of a pharmacological response or change its severity. Therefore, it is possible to put forward a hypothesis about the potentiation of the antidiabetic action of phenolic compounds when they exist in the form of mineral complexes.Aim. To carry out a comparative assessment of the antidiabetic activity of the mineral complex rutin with zinc in comparison with precursor substances and extraction from blueberry shoots to predict the effect of elements on the course of this pathology.Materials and methods. The objects of the study were an aqueous solution (C = 0.18 mg/ml) of a model complex of rutin with zinc with a molar ratio of components of 1 : 1 and blueberry shoots purchased from a pharmacy in St. Petersburg. According to the information on the packaging, the region of raw material procurement is Altai Territory, Barnaul, the period for harvesting blueberries is July 2020. The complex of rutin with zinc was obtained according to the method described in the literature from the pharmaceutical substance rutin (Rutin, batch 332, valid until 26.03.2023, Sichuan Guangsong Pharmaceutical Co., Ltd., China, FS 000569-060514) and an aqueous solution (С = 0.13 mg/ml) zinc chloride (Zinc chloride, batch 39/G 4, valid until 09.10.2021, Neva Reaktiv, Russia, STP TU COMP 1-533-2012). The optimal ratio of components 1 : 1 for the formation of a mineral complex was established by us earlier experimentally using the Job's method. The mass of zinc chloride, which must be added to the extraction, and the mass of the complex for the preparation of its aqueous solution were calculated on the basis of the quantitative content of biologically active substances in blueberry shoots and the molar ratio of the components involved in the formation of the complex compound determined by the spectral method. The quantitative content of the main groups of biologically active substances (flavonoids, hydroxycinnamic acids, organic acids) was determined spectrophotometrically on SF-2000 instrument (Russia) and titrimetrically using the methods presented in Russian Pharmacopoeia XIV FS.2.5.0093.18 and FS.2.5.0012.15. The antidiabetic effect of the complex of rutin with zinc was evaluated in comparison with an aqueous extract from the shoots of common blueberries (the ratio of raw materials: extractant – 1 : 80), an aqueous solution of zinc chloride (concentration – 0.36 mg/ml) and their mixture (ratio 1 : 1) on a model of dexamethasone-induced type 2 diabetes mellitus in laboratory animals. Determination of blood glucose concentration was carried out using a portable glucometer "AccuChek Active" (Roche Diabetes Care, Germany). The presence of glucosuria and ketonuria was established using Ketoglyuk-1 test strips (Biosensor AN, Russia). Statistical processing of the results was carried out using the Microsoft Excel program according to OFS.1.1.0013.15.Results and discussion. The results of the content of glucose and ketones in urine showed that in the process of modeling diabetes mellitus, glucosuria and ketonuria are characteristic for all groups of animals, which confirmed the formation of a pathological process in rats. A lower content of glucose and ketones in urine was found in a group of animals that received a complex of rutin with zinc (glucose concentration – less than 2.3 mmol/l, ketone concentration – less than 0.2 mmol/l). Measurement of the concentration of glucose in the blood showed that the complex of rutin with zinc has the most pronounced hypoglycemic effect, while the water extract from blueberry shoots and an aqueous solution of zinc chloride have a minimal antidiabetic effect (blood glucose is 6.9 mmol/l versus 8,1 mmol/l and 7.9 mmol/l, respectively).Conclusion. The study of the influence of elements in the composition of phenolic complexes on the course of diabetes mellitus showed that the introduction of minerals has a positive effect on the severity of the pharmacological effect, which can serve as confirmation of the hypothesis about the potentiation of the antidiabetic effect of phenolic compounds when they exist in the form of mineral complexes. Thus, the complex of rutin with zinc showed the maximum activity in comparison with the solution of zinc chloride, extraction from blueberry shoots and their mixture, which suggests that the form of existence of natural phenolic compounds in the composition of mineral complexes is optimal both from the point of view of accumulation and from the side manifestations of a pharmacological response. The results of the study create the preconditions for further study of the effect of various elements in combination with marker phenolic components of antidiabetic herbal preparations on the course of diabetes mellitus, and also make it possible to conclude that natural mineral complexes have a prophylactic effect against this pathology.