Antimalarial potential of Gymnema inodorum leaf extract and dihydroartemisinin combination against Plasmodium berghei infected mice

Abstract Chemotherapy plays a crucial role in malaria control. However, the main obstacle to treatment has been the rise of parasite resistance to most antimalarial drugs. Artemisinin-based combination therapies (ACTs) remain today’s most effective antimalarial therapies. However, malaria parasite tolerance to ACTs is now increasingly prevalent, especially in Southeast Asia. Consequently, this creates the need for effective alternative antimalarials. Interestingly, the effectiveness of Gymnema inodorum leaf extract (GIE) as an antimalarial candidate was reported earlier. Therefore, this study sought to evaluate the antimalarial potential of dihydroartemisinin (DHA) based combination therapy with GIE against Plasmodium berghei in a mouse model. Drug assessment was carried out on P. berghei ANKA (PbANKA) using the standard 4-day test for determination of fifty percent effective dose (ED50) of DHA and GIE individually. Moreover, the combination of DHA and GIE was also evaluated based on fixed-ratio strategy, 100/0, 80/20, 60/40, 40/60, 20/80, and 0/100 of ED50 of DHA and GIE, respectively. Overall, 2 mg/kg and 100 mg/kg of DHA and GIE resulted in ED50 against PbANKA. In combination, the ratio of 60/40 (DHA/GIE) had a considerable the highest antimalarial activity significantly (p < 0.001) against PbANKA with 88.95% inhibition that indicated a synergism efficacy (CI value = 0.68695). Additionally, this ratio was protected PbANKA infected mice from BW loss and PCV reduction with prolonged survival time throughout the 30 day follow up. This study points to better efficacy of GIE as an alternative drug partner in combination to enhance antimalarial efficacy of DHA against PbANKA infected mice.