The rising prevalence of diabetes and the high cost of treatment necessitate the search for natural, safe, and effective treatment methods. This study examined the in vitro and in silico pancreatic lipase inhibitory activity as well as the hypoglycemic effect of the ethanol extract of Tapinanthus cordifolius (TC) leaves in mice. TC leaves were extracted with ethanol by Soxhlet extraction technique. The pancreatic lipase inhibitory activity of TC extract at various concentrations (50, 100, 200, 400, 800, and 1600 µg/mL) was evaluated using spectrophotometric method. The effect of bioactive compounds from TC extract on pancreatic lipase was assessed in silico using molecular docking approach. The hypoglycaemic effect of TC extract was evaluated in vivo by an oral glucose tolerance test (OGTT) in normoglycaemic mice. Glibenclamide (5 mg/kg) was used as the positive control. TC extract showed significant pancreatic lipase (PL) inhibitory activity with IC50 value of 294.30 ± 0.67 µg/mL, which was comparable to that of orlistat (IC50 = 195.70 ± 4.60 µg/mL). In silico studies identified campesterol, heptadecafluorononanoic acid, α-tocopherol-β-d-mannoside, clionasterol, and β-tocopherol as potent pancreatic lipase inhibitors. TC extract (200, 400, and 800 mg/kg) significantly reduced hyperglycemia in glucose-challenged mice. It exhibited a significant (p<0.05) increase in glucose absorption, similar to glibenclamide, with the most notable effect at 60 minutes post-glucose load. These findings suggest that Tapinanthus cordifolius leaf can effectively inhibit pancreatic lipase and reduce blood glucose levels, and may serve as a natural treatment alternative for diabetes mellitus.
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