Mechanism of Action of Natural Dipeptidyl Peptidase-IV Inhibitors (Berberine and Mangiferin) in Experimentally Induced Diabetes with Metabolic Syndrome

Background: Berberine (BER) and mangiferin are known natural dipeptidyl peptidase (DPP-IV) inhibitors. Hence, the study was designed to elucidate the mechanism of action of natural DPP-IV inhibitors (BER and MNG) in experimentally induced diabetes with metabolic syndrome. Aim: The aim of this study was to observe mechanism through which natural DPP-IV inhibitor works in diabetes with metabolic syndrome rat model. Materials and Methods: Wistar rats were fed high-fat diet for 10 weeks and challenged with streptozotocin (STZ) (40 mg/kg) at the 3 rd week (high-fat diabetic control [HF-DC] group). After the confirmation of metabolic syndrome in the setting of diabetes, monotherapy (metformin [MET], vildagliptin [VIL], BER, and MNG) and combination (MET + VIL, MET + BER, and MET + MNG) therapy was orally fed to these rats from the 4 th to 10 th weeks. Results: Insulin resistance (IR) was seen in the HF-DC group as indicated by raised homeostasis model assessment of IR (HOMA-IR) in HF-DC group as compared with normal control (NC) groups. The treatment groups reduced IR as shown by a decrease in HOMA-IR as compared with HF-DC group rats. The marked reduction ( P < 0.001) of beta-cell function was observed in the HF-DC group as a reduced level of HOMA for beta-cell function (HOMA-β) was found as compared with the NC group. Increases in HOMA-β as compared to the HFDC group were observed in the therapy groups. The treatment group significantly reduced cholesterol and atherogenic index. The treatment group showed significant preservation of beta-cell mass as per immunohistochemistry and significant anti-apoptotic activity as per Terminal Deoxyribonucleotidyl Transferase-Mediated dUTP Nick End Labeling assay report. The treated rats significantly ( P < 0.05) reduced high-sensitivity C-reactive protein. Lipid peroxidation (thiobarbituric acid reactive substances) marker ( P < 0.001) was significantly reduced in the treatment group. Conclusion: The natural DPP-IV inhibitors BER and MNG treatment showed beneficial effects on various components of metabolic syndrome.