Mehani formulation is rich in bioactive compounds and ameliorates diabetes and associated inflammatory condition - In vitro and in vivo studies

Mehani, a polyherbal formulation (PHF) containing five herbs has been used in the diabetes treatment for more than 20 years in India. Few data are available for its polypharmacological properties in treating interlinked diseases. Hence, the present study investigates the in vitro and in vivo antidiabetic and associated anti-inflammatory activity of Mehani. Glucose uptake activity of aqueous and hydroalcoholic extracts of PHF, individual herbs and sub fractionations (alkaloid, polyphenol) were evaluated in C2C12 mouse skeletal muscle cells. In vitro antidiabetic enzymatic assay, anti glycation activity was assessed for all the extracts. Active compounds were determined using HPLC analysis. Genes involved in glucose uptake and inflammatory pathways at mRNA level, GLUT4 protein expression and translocation were analyzed. Also, In vivo hypoglycemic, hypolipidemic and antioxidant activities were investigated in the best acting extracts in diabetic wistar rats. Aqueous (AQF) and polyphenolic (PPF) extracts showed insulin stimulated glucose uptake of 2.2±0.26 and 2.0±0.13 fold when compared to the untreated control. AQF exerted anti hyperglycemic action on GLUT4 via PI3K-AKT pathway, while PPF via AMPK pathway. Both inhibited the LPS induced activation of TNFα, IL6 and IL10 cytokines at mRNA level. Particularly, AQF showed increased GLUT4 protein expression and translocation. Gallic acid, cinnamic acid derivatives and D-pinitol (new finding) were the major bioactives identified through HPLC analysis. AQF (400 mg/kg b.w) treated diabetic rats showed significant reduction in blood glucose, HbA1c levels after 21 days of treatment. Increased serum cholesterol (67.5± 3.53 mg/dL), TGL (123.5±3.53) levels in diabetic rats were significantly reduced in AQF treated rats. Also, improvement in the antioxidant levels (SOD, CAT, GSH and GST) with reduction in liver enzymes was observed. AQF possessed hepatoprotective and renoprotective activities and efficiently restored the pancreatic beta cell integrity. To conclude, aqueous Mehani extract can be used as a safe, complimentary medicine to treat diabetes and associated diseases.