Novel Insights Into the Bioactive Profile and Therapeutic Potentials of Indonesian <i>Annona muricata</i> Leaves

This study investigates, for the first time, the comprehensive pharmacological profile of the aqueous extract of Annona muricata L. (graviola) leaves from Indonesia, focusing on its antioxidant, antinociceptive, and anti-inflammatory properties, alongside its acute toxicity and phytochemical composition. The extract, obtained through cold maceration, was rich in phenolic compounds, including gallic acid, catechin, quercetin, and rutin, as revealed by phytochemical analysis. It exhibited strong antioxidant capacity in both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing antioxidant power (FRAP) assays. Acute toxicity testing indicated no adverse effects at doses up to 5000 mg/kg, confirming its safety. Notably, the extract produced significant antinociceptive effects in hot plate, acetic acid-induced writhing, and formalin tests and exerted marked anti-inflammatory activity in both xylene-induced ear edema and carrageenan-induced paw edema models, comparable to the standard drug indomethacin. These findings not only support the traditional use of A. muricata in pain and inflammation relief but also provide novel evidence of its therapeutic potential as a safe, natural source of bioactive compounds with multiple pharmacological effects.