Comparative Metabolomic Profiling and Antihyperglycemic Activity of <i>Artabotrys hexapetalus</i> and <i>Artabotrys siamensis</i> Leaf Extracts: In Vitro and In Silico Studies

Abstract

Artabotrys species have been traditionally used for managing diabetes; however, their bioactive components remain insufficiently explored. This study evaluated the antihyperglycemic potential of Artabotrys hexapetalus and Artabotrys siamensis leaf extracts by identifying their major active components and assessing their inhibitory effects on key carbohydrate-metabolizing enzymes through gas chromatography-mass spectrometry profiling, docking, and in vitro assays. Metabolite profiling revealed brassicasterol (19.33%), β-caryophyllene (12.3%), 1-hexacosanol (10.82%), and chondrillasterol (8.62%) as major compounds in A. hexapetalus, whereas A. siamensis showed 22-dihydrospinasterol acetate (8.13%), 1-hexacosanol (6.55%), and brassicasterol (6.47%). Molecular docking studies revealed strong binding affinities of phytosterols (brassicasterol, chondrillasterol, and 22-dihydrospinasterol acetate) to α-amylase and α-glucosidase with binding energies ranging from -7.4 to -9.2 kcal/mol, outperforming the reference drug acarbose. In vitro inhibition assays confirmed that A. hexapetalus demonstrated superior inhibition of both enzymes with half-maximal inhibitory concentration values (IC₅₀) of 0.139 and 0.255 mg/mL for α-amylase and α-glucosidase, respectively, compared to A. siamensis (0.249 and 0.709 mg/mL) and acarbose (0.084 and 0.551 mg/mL), respectively. These findings suggest promising antihyperglycemic potential of A. hexapetalus and A. siamensis, attributed to their bioactive phytosterols in their hexane extracts.