ANTIDIABETIC AND ANTIDYSLIPIDEMIC ACTIVITY OF ETHYL ACETATE FRACTIONS OF XYLOCARPUS GRANATUM AND XYLOCARPUS MOLLUCCENSIS ON HIGH FRUCTOSE HIGH FAT AND HIGH SUCROSE HIGH FAT FED-LOW DOSED STREPTOZOTOCIN TREATED DIABETIC RATS

Objectives: The present study was carried out to investigate the antidiabetic and antidyslipidemic effect of standardized fractions of X. granatum (CDR-134 F194) and X. molluccensis (CDR-267 F018) by measuring the status of blood glucose, serum insulin, lipid levels, hepatic and renal function markers of high fructose high fed streptozotocin treated rats and high sucrose high fat diet fed-low dosed Streptozotocin treated diabetic rats.Methods: Male rats of Sprague Dawley strain of body weight around 150 g when kept on high fructose high fat diet and high sucrose high fat diet for two weeks, respectively, showed abnormal glucose tolerance, dyslipidemia and obesity and at this stage when streptozotocin was given intraperitoneally at 45.0 mg/kg body weight caused persistent hyperglycemia in them addition to dyslipidemia along with impairment in their hepatic and renal functions.Results: The standardized fractions of X. granatum (CDR-134 F194) and X. molluccensis (CDR-267F018) when given to these high fructose high fat fed low dosed streptozotocin treated diabetic rats or high sucrose high fat diet fed-low dosed streptozotocin treated diabetic rats for 10 consecutive days showed significant improvement in their glucose intolerance, decline in their serum triglycerides and LDL-cholesterol levels. These CDR-134 F194 and CDR-267 F018 treated rats also showed elevation in their HDL-cholesterol levels and improvement in their hepatic and renal functions as evidenced by decline in SGOT, SGPT, urea, uric acid and creatinine levels.Conclusion: The present study thus concludes that the antidiabetic efficacy of standardized fractions of X. granatum (CDR-134 F194) and X. molluccensis (CDR-267F018) have favorable effect in bringing down the severity of hyperglycemia, hyperlipidemia, decline the increased level of renal and hepatic function markers and also improving glucose tolerance activity

ANTIHYPERGLYCEMIC AND ANTIDYSLIPIDEMIC ACTIVITY IN ETHYL ACETATE FRACTION OF THE FRUITS OF XYLOCARPUS GRANATUM AND XYLOCARPUS MOLUCCENSIS

Objectives: Although various species of Xylocarpus i. e. Granatum, moluccensis are known for their medicinal properties. Yet, its anti-diabetic activity remains to be defined. So the aim of this study was to evaluate the antihyperglycemic and antidyslipidemic activity in ethyl acetate fraction of the fruits of X. granatum and X. moluccensis on validated animal models as well as in-vitro glucose uptake stimulatory effect and their cytotoxicity effect in L6 skeletal muscle cells.Methods: The ethyl acetate fraction of the fruits of X. granatum and X. moluccensis were administered to diabetic groups daily up to 10 days for prolonged study. Biochemical parameters notably glucose tolerance, insulin level, lipid profile were assessed. The ethyl acetate fraction of the fruits of X. granatum and X. moluccensis were also tested for glucose uptake effect by skeletal muscle cells in the concentration dependent manner.Results: The present study show that the ethyl acetate fraction of the fruits of X. granatum as well as X. moluccensis are effective in improving glucose tolerance, declining blood glucose as well as serum cholesterol and triglycerides levels in low dosed streptozotocin-induced diabetic rats and dyslipidemic hamsters, respectively. These fractions were also found efficient in increasing glucose uptake by L6 skeletal muscle cells but did not show any effect on cell viability of L6 skeletal muscle cells.Conclusion: Based on the results, the present study revealed that ethyl acetate fraction of the fruits of X. granatum and X. moluccensis lowered blood glucose profile by increasing the glucose uptake by L-6 and this may be the possible mechanisms for the antidiabetic and antidyslipidemic action

Assessment of the dual role of Lyonia ovalifolia (Wall.) Drude in inhibiting AGEs and enhancing GLUT4 translocation through LC-ESI-QTOF-MS/MS determination and in silico studies

Introduction: Diabetes mellitus (DM) is a metabolic disorder that results in glucose accumulation in the blood, accompanied by the production of advanced glycation end products (AGEs) through glycation of cellular proteins. These AGEs interfere with insulin signaling and prevent GLUT4 membrane translocation, thereby promoting the accumulation of more glucose in the blood and causing post-diabetic complications.Methods: In this study, we examine the anti-diabetic potential of Lyonia ovalifolia (Wall.) Drude, a well-known ethnomedicinal plant of the Indian Himalayas. Considering its various medicinal properties, we analyzed its ethanolic extract and various solvent fractions for in vitro antiglycation activity and antidiabetic potential, i.e., stimulation of GLUT4 translocation.Result and Discussions: The results showed that the extract and fractions exhibited increased antiglycation activity and an increased level of GLUT4 translocation. Analysis of a further 12 bioactive compounds of ethanolic extract, identified through LC-ESI-QTOF-MS/MS, revealed the presence of three new compounds: leucothol B, rhodoterpenoids A, and leucothol A. Moreover, we performed molecular docking of identified compounds against key proteins of diabetes mellitus: the sirtuin family of NAD (+)-dependent protein deacetylases 6 (SIRT6), aldose reductase (AR), and tyrosine kinase (TK). The results showed that flavonoid luteolin showed the best binding affinity ((−12.3 kcal/mol), followed by eriodictyol, astilbin, and syringaresinol. An ADMET study showed that luteolin, eriodictyol, astilbin, and syringaresinol may be promising drug candidates belonging to the flavonoid class of compounds, with no harmful effects and complying with all the drug-likeness guidelines. Furthermore, molecular dynamics (MD) simulations on a 50 ns timescale revealed that AR protein was most stable with luteolin throughout the simulation period. Therefore, this study reveals for the first time that L. ovalifolia plays an important role in insulin homeostasis, as shown in in vitro and in silico studies

<span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Antidiabetic activity of heart wood of <i style="mso-bidi-font-style:normal">Pterocarpus marsupium</i> Roxb. and analysis of phytoconstituents^†</span>

363-374The crude powder, ethanolic extract and aqueous, chloroform, hexane and n-butanol soluble fractions of ethanolic extract of heart wood of P. marsupium showed marked improvement on oral glucose tolerance post sucrose load in normal rats. All these fractions except aqueous fraction showed improvement on oral glucose tolerance post sucrose load on streptozotocin (STZ)-induced diabetic rats. The crude powder, ethanolic extract and hexane and n-butanol fractions showed marked decline in blood glucose level on STZ-induced diabetic rats. The ethanolic extract (100 mg/kg body weight) when given to STZ-induced diabetic rats for 10 consecutive days declined blood glucose, improved OGTT and increased their serum insulin levels. The ethanolic extract also showed marked improvement on oral glucose tolerance on high fat-low dosed STZ-induced diabetic rats and neonatally STZ treated rats. The ethanolic extract of P. marsupium also showed marked antidyslipidemic effects on high fat diet fed Syrian golden hamsters. Altered renal and hepatic function markers and serum insulin levels of high fat diet fed-low dosed STZ-treated diabetic rats were also found towards normalization when these animals were treated with ethanolic extract of P. marsupium for 28 consecutive days. The four out of five phenolic C-glycosides isolated from n-butanol fraction of ethanolic extract of P. marsupium enhanced glucose uptake by skeletal muscle cells (C2C12) in a dose dependent manner. It may primarily be concluded that phenolic-C-glycosides present in P. marsupium heart wood are the phytoconstituents responsible for the antihyperglycemic activity and validate the claim of antidiabetic activity of heart wood of <i style="mso-bidi-font-style: normal">P. marsupium