Validation of the antihyperglycaemic and hepatoprotective activity of the flavonoid rich fraction of Brachychiton rupestris using in vivo experimental models and molecular modelling.

Oxidative stress leads to many disorders as diabetes mellitus and liver diseases. This study evaluates the antihyperglycemic and hepatoprotective activities of Brachychiton rupestris (Malvaceae). The antihyperglycemic activity of the total methanol extract of B. rupestris leaves (BRT) and its ethyl acetate fraction (BRE) was evaluated using streptozotocin induced diabetic rats. The hepatoprotective activity was assessed using carbon-tetrachloride induced hepatotoxicity. Oral administration of 50 mg/kg b.wt (body weight) of BRT and BRE to Streptozotocin -diabetic rats caused a notable decrease in serum glucose by 39.38 and 42.09% with 35.62 and 15.44% increase in serum insulin, respectively, compared with Streptozotocin-diabetic rats. Oral administration of BRT and BRE to carbon-tetrachloride -treated rats (50 mg/kg b.wt) resulted in reduction in serum aspartate transaminase (AST) (28.88 and 27.2%, respectively) and alanine transaminase (ALT) (8 and 13.56%) levels, respectively. They also ameliorated oxidative stress in both models as evidenced from oxidative stress markers. Liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS) analysis of the most active fraction (BRE) identified nine compounds including flavonoids and phenolic acids. Molecular modelling of the identified compounds was performed on human pancreatic α-amylase (HPA) and human α-glucosidase (HAG) using Discovery Studio 2.5. Quercetin-3-O-(6″-O-α-l-rhamnopyranosyl)-β-D-glucoside showed the greatest affinity towards both HPA and HAG. Thus, this study provided scientific evidence on the antihyperglycemic and hepatoprotective activities of Brachychiton rupestris.