Evaluation of the Antidiabetic Effect of Clerodendrum volubile P. Beauv leaves : In vivo and In Silico Approach

Clerodendrum volubile leaf is commonly used in traditional medicine for the management of various diseases including diabetes in Nigeria. This study sought to propose the possible mechanism underlying the antidiabetic effect of C. volubile leaves in streptozotocin (STZ)‐induced diabetic rats using in vivo and in silico approach. Aqueous extract of C. volubile was prepared and its effect assessed on relevant enzymes associated with diabetes. Fifty Male Wistar rats (n=5) were randomly separated into ten groups. The induction of diabetes in rats was by a single intraperitoneal injection of STZ (65 mg/kg body weight) while C. volubile extract was administered orally to diabetic and non‐diabetic animals, at the doses of 50,100 and 200 mg/kg body weight respectively for 14 days. Also the interaction of compounds identified from C. volubile (HPLC‐DAD) on Takeda‐G‐protein‐receptor‐5 (TGR5), peroxisome proliferated activated receptor gamma (PPARγ) and dipeptidyl‐peptidase 4 (DPP‐4) was also investigated through molecular docking. Administration of C. volubile extract significantly reduced the elevated plasma glucose level and body weight, improved kidney functions, attenuated oxidative stress by decreasing malondialdehyde (MDA) levels, enhancing superoxide dismutase, catalase and glutathione peroxidase activities, reinstated the lipid profiles to nearly normal level and restored pancreatic histological integrity in diabetic rats. Rutin ranked highest among all the compounds identified in C. volubile with −8.3 kcal/mol binding energy with TGR5 with Glu343 and Glu291 −7.9 kcal/mol (PPARγ) and −9.5.kcal/mol (DPP‐4). Gln77, Arg125, Tyr240, Glu291, Glu343, Tyr 662 are among residues enhancing rutin binding to these proteins. The results revealed that C. volubile possess antidiabetic effects through the modulation of TGR5, PPARγ and DPP4. Rutin might be the lead compounds responsible for the antidiabetic effect of C. volubile justifying the use of this plant in traditional medicine