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 (I_GABA) of <i>H. revolutum</i> 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 I_GABA (GABAergic effect) through GABA_A receptors heterologously expressed in <i>Xenopus</i> oocytes. Xanthones 4-hydroxy-2,3-dimethoxy-9<i>H</i>-xanthen-9-one (<b>1</b>), 3-hydroxy-2,4-dimethoxy-9<i>H</i>-xanthen-9-one (<b>2</b>) and <i>trans</i>-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-5-methoxy-2,3-dihydro-<i>7H</i>-[1,4]dioxino[2,3-c]xanthen-7-one (<b>3</b>) were isolated from the stem and tested in the GABA_A receptors assay, but only <b>3</b> was assessed for α-glucosidase-inhibitory action. Compared to acarbose (IC₅₀ = 6.16 µM), <b>3</b> 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 <b>1</b> and <b>2</b> significantly enhanced I_GABA with similar efficacy, while <b>3</b> was inactive, which may be attributed to its notable structural difference (cyclic ether substitution) compared to compounds <b>1</b> and <b>2</b>. <i>H. revolutum</i> stem contains xanthones with α-glucosidase-inhibitory potential, which also enhance I_GABA and could be further studied as a medicinal plant for managing GABA_A receptor-mediated mental disorders and/or diabetes.