Abstract
Malaria continues to be a significant global health burden, with over 249 million cases and 619,000 deaths reported in 2022, primarily affecting tropical and subtropical regions. The emergence of drug-resistant strains of Plasmodium falciparum has reduced the efficacy of artemisinin-based combination therapies (ACTs), necessitating the exploration of alternative treatment strategies. This study investigates the antimalarial efficacy of Tinospora crispa extract (TCE) and artesunate (ART) against Plasmodium berghei ANKA infection in ICR mice. Both ART and TCE demonstrated dose-dependent antimalarial activity, with effective doses (ED(50)) of 200.31 mg/kg and 1.96 mg/kg, respectively. The combination of ART and TCE exhibited synergistic effects, achieving significantly higher parasitemia inhibition compared to monotherapy, with combination index (CI) values < 1 at ED(50), ED(50/2), and ED(50/4). Furthermore, combination therapy provided enhanced protection against packed cell volume (PCV) reduction and body weight (BW) loss, along with prolonged mean survival time (MST) compared to untreated and single-treatment groups. These findings highlight the potential of combining TCE with ART as a novel antimalarial strategy, offering synergistic benefits that may mitigate drug resistance and improve treatment outcomes. Further studies are warranted to explore the molecular mechanisms underlying these interactions and to evaluate the efficacy of this combination in clinical settings.