Abstract

The growing resistance to first-line artemisinin-based therapies underscores the urgent need for novel antimalarial agents, with medicinal plants offering a promising source of candidates. Phikud Navakot formulation and its component plants are widely used in traditional medicine; however, their antimalarial properties remain underexplored. This study aimed to screen the Phikud Navakot formulation and its individual component plants for antiplasmodial activity and to further evaluate the most potent extract through in vivo efficacy testing, acute toxicity assessment, and phytochemical profiling. In vitro antiplasmodial activity was evaluated against a chloroquine-resistant Plasmodium falciparum K1 strain, and in vivo efficacy was assessed using the standard 4-day suppressive test in P. berghei ANKA–infected mice. Acute oral toxicity was examined in mice at a limit dose of 2000 mg/kg. Among all crude extracts tested, the aqueous gall extract of Terminalia chebula exhibited potent in vitro antiplasmodial activity (IC<inf>50</inf> = 3.24 ± 0.83 μg/mL) without toxicity (CC<inf>50</inf> > 100 μg/mL) in Vero cells or hemolytic effects. In the 4-day suppressive test, mice treated with 200, 400, and 600 mg/kg doses of the aqueous T. chebula gall extract showed significant, dose-dependent suppression of parasitemia (38.88%, 47.08% and 60.61%, respectively; p < 0.05). Furthermore, no signs of acute toxicity were observed at the 2000 mg/kg dose. Phytochemical profiling indicated that the aqueous T. chebula gall extract contains multiple bioactive compounds with potential medicinal properties. Overall, these findings demonstrate that the aqueous T. chebula gall extract possesses promising both in vitro and in vivo antimalarial activities, with an excellent safety profile. This provides scientific evidence supporting its potential as a plant-based candidate for antimalarial drug development. Further studies are warranted to isolate the active constituents, elucidate their mechanisms of action, and conduct subacute toxicity studies to extend the safety evaluation beyond the current findings.