Background: Diabetes mellitus co-existing with metabolic syndrome has become a common predicament in society due to Obesity, change in lifestyle and dietary habits. With this point of view the study was designed to find out natural source of drug efficacious in Obesity with diabetes co-existing with metabolic syndrome.

Objectives: To screen the medicinal plant( Berberine and Mangiferin) for DPP-IV Inhibitory activity and studied for efficacy and mechanism in animal model of diabetes with metabolic syndrome.

Material & Methods: After 3 weeks of dietary manipulation, rats were injected intraperitoneally with STZ (40 mg/kg). Elevated blood glucose (>200 mg/dl), triglyceride (>150 mg/dl) and reduced HDL cholesterol levels (<35mg/dl) and increase weight confirmed development of metabolic syndrome along with diabetes in rats. There after the rats were either fed normal diet or HFD as per the protocol for 10 weeks.

Results:. Berberine and Mangiferin treatment (Monotherapy and combination therapy) showed beneficial effects on various component of metabolic syndrome: Hyperglycemia (Significant reductions in blood glucose, HbA1c, HOMA-IR, increase in serum insulin, C-peptide, HOMA-β), dyslipidemia (Significant decrease in TG, TC & increase in HDL-C) and elevated blood pressure (Reduction in systolic and diastolic blood pressure) as compared with HF-DC group. Berberine and Mangiferin treatment significantly reduced serum DPP-IV levels which correlated with its beneficial effects in diabetes with metabolic syndrome. The Immunohistochemical localization of Insulin suggested that Berberine and Mangiferin preserved pancreatic beta cell mass by virtue of its anti-apoptotic activities. DPP-IV inhibitory confirmed by Invitro and in silico docking studies against crystal structure of DPP-IV. The Berberine and mangiferin posses antioxidant property and safe to Kidney, Liver , Heart and pancreas.

Conclusion: The Berberine and Mangiferin were efficacious in attenuating the deleterious changes induced by diabetes and metabolic syndrome.

Kew words: Diabetes, Obesity, berberine, mangiferin