Abstract

Malaria remains a global health challenge, exacerbated by the emergence of drug-resistant Plasmodium strains. This study evaluates the antimalarial activity of Picrasma javanica stem bark extract and its combination with artesunate (ART) in Plasmodium berghei–infected mice. The extraction yield using hexane at a 1:5 (w/v) ratio was 7.8% w/w. Acute toxicity assessment indicated no mortality or adverse effects at doses up to 2000 mg/kg. In suppressive activity tests, P. javanica stem bark extract exhibited dose-dependent efficacy, achieving 13.3%, 36.4%, and 52.5% parasitemia inhibition at doses of 100, 200, and 400 mg/kg, respectively, with significant inhibition at higher doses (p < 0.05 and p < 0.01). ART showed 90.7% suppression (p < 0.001). In curative tests, the extract at 400 mg/kg reduced parasitemia by 31.0% (p < 0.05), while ART achieved 75.3% suppression (p < 0.001). The effective dose (ED<inf>50</inf>) values were 404.9 mg/kg for P. javanica stem bark extract and 2.03 mg/kg for ART. Combination treatments at ED<inf>50</inf> ratios of 40/60 and 20/80 (extract/ART) resulted in 65.9% (p < 0.01) and 81.7% (p < 0.001) inhibition, respectively, with the 20/80 ratio showing a significant synergistic interaction (CI = 0.44121). The mean survival time (MST) for the untreated group was 12.2 ± 1.9 days. P. javanica stem bark extract and ART alone extended MST to 21.4 ± 2.4 and 21.8 ± 2.4 days, respectively (p < 0.05), while the 20/80 combination achieved the longest MST of 28.6 ± 1.7 days (p < 0.01; p < 0.05 vs. monotherapies). These findings highlight the potential of P. javanica stem bark extract as a complementary antimalarial agent when used with ART, offering a promising approach for combating drug-resistant malaria.