Antioxidant, Alpha‐Amylase Inhibitory and Hypoglycemic Activity of <i>Smallanthus sonchifolius</i> Leaves from Nepal: An Integrated In Vitro, In Vivo, and In Silico Approach

In 2019, diabetes mellitus affected 9.3% of the global population and accounted for one in nine adult deaths. Plant-based antioxidants neutralize harmful free radicals, mitigate oxidative stress, and significantly prevent diabetes and its complications. This study evaluated the in vitro antioxidant, alpha-amylase inhibitory, in vivo oral hypoglycemic, and <i>in silico</i> antidiabetic potential of <i>Smallanthus sonchifolius</i> (<i>S. sonchifolius</i>) leaf extract. Mice (<i>n</i> = 25) were divided into five groups after a 16-h fast with access to water. The groups received distilled water (normal control), metformin (100 mg/kg, standard), or <i>S. sonchifolius</i> ethanolic extract at 100, 250, or 500 mg/kg to compare the antidiabetic potential of the extract with that of the control. Fasting blood glucose levels were measured in tail vein blood before the experiment and at 30, 60, and 120 min post-administration to evaluate the hypoglycemic activity of the extract and standard drug. The ethanolic extract exhibited dose-dependent alpha-amylase inhibition (IC₅₀ value 0.136 mg/mL) and significant hypoglycemic effects, reducing blood glucose levels similar to those of the standard drugs voglibose and metformin. The maximum blood glucose reduction was 17.99% and 15.74% in the normal and glucose-loaded mice, respectively, at 500 mg/kg within 120 min. <i>In silico</i> analysis shows, polymatin B and chlorogenic acid demonstrating the highest binding affinity of -8.2 and -7.2 kcal/mol, respectively, in PPAR-γ (3G9E). Polymatin B and chlorogenic acid showed strong binding affinities of -7.3 and -7.5 kcal/mol, respectively, in alpha-amylase (4W93). These findings indicate that <i>S. sonchifolius</i> possesses significant hypoglycemic and antioxidant properties, suggesting its potential as an antidiabetic agent, warranting further clinical research.