Dodonaea viscosa hydroethanolic leaf extract: A potent anti-obesity/anti-diabetic therapeutic; in vivo and in silico investigatio

Medicinal plants are being considered promising agents for disease management because of their diverse pharmacological potential. The current study explored the antiobesity/antidiabetic efficacy of Dodonaea viscosa ( D . viscosa ) hydroethanolic leaf extract using in-vivo and in-silico techniques. The in-vivo study was conducted using a mouse model to evaluate the effectiveness of the hydroethanolic extract of D . viscosa . The alloxan-induced high-fat diet-fed obese diabetic mice were treated with hydroethanolic extract at a dose of 150 (Plant extract dose-I, PED-I) and 300mg/kg body weight (Plant extract dose-II, PED-II) in comparison with the groups treated with orlistat and glucophage. The body weight (g), blood glucose level (mg/dL), total cholesterol (mg/dL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), histopathological analysis of vital organs, etc., were conducted and compared. Molecular docking of the identified metabolites was also performed to elucidate the molecular interactions most likely responsible for their therapeutic action. The results of in-vivo studies revealed a significant reduction in total cholesterol as the value for the untreated obese diabetic group (UODG) was 225 ± 3.9 mg/dL, which reduced to 145.5±3.2 mg/dL upon administering plant extract at a dose of 300 mg/kg of body weight, with significant modulations in HDL and LDL. The blood glucose levels decreased from 354.7± 7.9 to 121±3.2 mg/dL upon administration of the extract. Similarly, the ALT value of mice was reduced from 105.6± 6.1 to 54±4.3 U/L, and the AST value was lowered to 36.7±4.3 from 85.2±4.2 U/L. The histopathological examination further elaborated the possible improvement in cellular vacuolization. The findings revealed that treatment of obese-diabetic mice with the hydroethanolic extract of D. viscosa displayed anti-obesity/anti-diabetic effects, as evidenced by reduced blood glucose levels and improved lipid profiles, accompanied by histopathological improvements. The observed impact may be attributed to the presence of biologically active metabolites/compounds in the plant extract, which is also supported by in-silico studies. The molecular docking provided a deep insight into the molecular targets and interactions most probably responsible for the therapeutic potential of metabolites present in the plant extract. Out of 29 compounds, 16 were screened out. Among the screened compounds, molecular docking analysis showed that isaindigotidione (-7.21 kcal/mol) and gomisin D (-7.49 kcal/mol) exhibited the most favorable binding energies with α-amylase, while cnidimol-F (-6.84 kcal/mol) and several other metabolites also showed promising interactions with α-amylase active site residues. The hydroethanolic leaf extract of D. viscosa exhibited promising potential to be employed as an effective therapeutic agent for the simultaneous management of obesity and diabetes.