Effects of 22 traditional anti-diabetic medicinal plants on DPP-IV enzyme activity and glucose homeostasis in high-fat fed obese diabetic rats

The present study investigated the effects of hot water extracts of 22 medicinal plants used traditionally to treat diabetes on Dipeptidyl peptidase-IV (DPP-IV) activity both in vitro and in vivo in high-fat fed (HFF) obese-diabetic rats. Fluorometric assay was employed to determine the DPP-IV activity. For in vivo studies, HFF obese-diabetic rats were fasted for 6 h and blood was sampled at different times before and after the oral administration of the glucose alone (18 mmol/kg body weight) or with either of the four most active plant extracts (250 mg/5 ml/kg, body weight) or established DPP-IV inhibitors (10 μmol/5 ml/kg). DPP-IV inhibitors: sitagliptin, vildagliptin and diprotin A, decreased enzyme activity by a maximum of 95-99% (P<0.001). Among the 22 natural anti-diabetic plants tested, AnogeissusLatifolia exhibited the most significant (P<0.001) inhibitory activity (96 ± 1%) with IC50 and IC25 values of 754 and 590 μg/ml. Maximum inhibitory effects of other extracts: Aegle marmelos, Mangifera indica, Chloropsis cochinchinensis, Trigonella foenum-graecum and Azadirachta indica were (44 ±7%; 38 ± 4%; 31±1%; 28±2%; 27±2%, respectively). A maximum of 45% inhibition was observed with >25 μM concentrations of selected phytochemicals (rutin). A.latifolia, A. marmelos, T. foenum-graecum and M. indica extracts improved glucose tolerance, insulin release, reduced DPP-IV activity and increased circulating active GLP-1 in HFF obese-diabetic rats (P<0.05-0.001). These results suggest that ingestion of selected natural anti-diabetic plants, in particular A. latifolia, A. marmelos, T. foenum-graecum and M. indica can substantially inhibit DPP-IV and improve glucose homeostasis, thereby providing a useful therapeutic approach for the treatment of T2DM.