GABAergic and α-Glucosidase-Inhibitory Potentials of Fractions and Isolated Xanthones from Hypericum revolutum Vahl subsp. revolutum

This study aimed to investigate the glycaemic control potential and modulation of GABA-induced chloride currents (IGABA) of H. revolutum and the possible bioactive xanthones. Fractions from the leaf and stem extracts (dichloromethane and methanol) were assessed for in vitro α-glucosidase-inhibitory potential and their ability to modulate IGABA (GABAergic effect) through GABAA receptors heterologously expressed in Xenopus oocytes. Xanthones 4-hydroxy-2,3-dimethoxy-9H-xanthen-9-one (1), 3-hydroxy-2,4-dimethoxy-9H-xanthen-9-one (2) and trans-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-5-methoxy-2,3-dihydro-7H-[1,4]dioxino[2,3-c]xanthen-7-one (3) were isolated from the stem and tested in the GABAA receptors assay, but only 3 was assessed for α-glucosidase-inhibitory action. Compared to acarbose (IC50 = 6.16 µM), 3 showed a mild to moderate α-glucosidase-inhibitory activity (IC50 = 45.1 µM), which may be attributed to the absence of a hydroxyl group at its xanthone core. Isomeric compounds 1 and 2 significantly enhanced IGABA with similar efficacy, while 3 was inactive, which may be attributed to its notable structural difference (cyclic ether substitution) compared to compounds 1 and 2. H. revolutum stem contains xanthones with α-glucosidase-inhibitory potential, which also enhance IGABA and could be further studied as a medicinal plant for managing GABAA receptor-mediated mental disorders and/or diabetes.