Evaluation of the Antioxidant, Antidiabetic, and Antiplasmodial Activities of Xanthones Isolated from Garcinia forbesii and Their In Silico Studies

Abstract

This study aimed to isolate xanthones from <i>Garcinia forbesii</i> and evaluated their activity in vitro and <i>in silico</i>. The isolated compounds were evaluated for their antioxidant activity by DPPH, ABTS and FRAP methods. The antidiabetic activity was performed against α-glucosidase and α-amylase enzymes. The antiplasmodial activity was evaluated using <i>Plasmodium falciparum</i> strain 3D7 sensitive to chloroquine. Molecular docking analysis on the human lysosomal acid-alpha-glucosidase enzyme (5NN8) and <i>P. falciparum</i> lactate dehydrogenase enzyme (1CET) and prediction of ADMET for the active compound, were also studied. For the first time, lichexanthone (<b>1</b>), subelliptenone H (<b>2</b>), 12b-hydroxy-des-D-garcigerrin A (<b>3</b>), garciniaxanthone B (<b>4</b>) and garcigerin A (<b>5</b>) were isolated from the CH₂Cl₂ extract of the stem bark of <i>G. forbesii</i>. Four xanthones (Compounds <b>2</b>-<b>5</b>) showed strong antioxidant activity. In vitro α-glucosidase test showed that Compounds <b>2</b> and <b>5</b> were more active than the others, while Compound <b>4</b> was the strongest against α-amylase enzymes. In vitro antiplasmodial evaluation revealed that Compounds <b>2</b> and <b>3</b> showed inhibitory activity on <i>P. falciparum</i>. Molecular docking studies confirmed in vitro activity. ADMET predictions suggested that Compounds <b>1</b>-<b>5</b> were potential candidates for oral drugs. The isolated <b>2</b>-<b>5</b> can be used as promising phytotherapy in antidiabetic and antiplasmodial treatment.