Background Due to the increasing resistance of malaria parasites to antimalarial drugs, medicinal plants are increasingly being employed to cure malaria. The purpose of this study is to establish the cytotoxicity, antioxidant, and antiplasmodial activity of a mixture of Terminalia macroptera and Erythrina sigmoidea extracts, two plants that have been traditionally used together in the management of malaria in Cameroon′s Western Region. Methods The stem bark extracts of both plants were formulated according to established protocols. Previous studies reported the use of blends of E. sigmoidea and T. macroptera in antiplasmodial assays employing established methods. Three combinations were used: 75% T. macroptera and 25% E. sigmoidea in Combination 1, 50% T. macroptera and 50% E. sigmoidea in Combination 2, and 25% T. macroptera and 75% E. sigmoidea in Combination 3. The in vitro antiplasmodial activity of the combinations against chloroquine‐sensitive (3D7) and chloroquine‐resistant (Dd2) Plasmodium falciparum strains was evaluated by the SYBR green fluorescence‐based assay. Antioxidant activity was evaluated by DPPH (1,1‐diphenyl‐2picrylhydrazyl), FRAP free radical scavenging (ferric reducing antioxidant capacity), H2O2 (hydrogen peroxide), and NO (nitric oxide) radical scavenging. Cytotoxicity of the extracts was evaluated by using Vero cell line and human donor red blood cells (RBCs). Docking studies were conducted using the Schrodinger Maestro software. Result Extracts of E. sigmoidea and T. macroptera were effective in all the three combinations. Being effective with IC 50 values of 4.64 ± 0.09 μ g/mL for the 3D7 strain and 4.67 ± 0.24 μ g/mL for the Dd2 strain of P . falciparum , the third combination proved to be the most effective. The free radical scavenging activity of all the plant extracts was good. Against DPPH, FRAP, NO, and H 2 O 2 , IC 50 values for the combination were 510.3 μg/mL, 159.6 μg/mL, and undetermined, respectively. Plant extract Combination 3 was not cytotoxic in cytotoxicity assay with CC 50 of 217.05 ± 0.21 μ g/mL against Vero cells and reduced hemolysis compared with positive control. Phytochemical analysis of plant extract identified the existence of alkaloids, triterpenoids, tannins, quinones, saponins, flavonoids, and phenolics. Sigmoidin A, Bidwillon A, Abyssinone V, Flavogallonic acid, 3,4,5‐tri‐O‐caffeoylquinic acid were the Top 5 ligands that had the highest docking scores. Compounds are docked to PfDHFR because it is an essential enzyme, a validated antimalarial drug target, and docking provides mechanistic insight, resistance relevance, and predictive support for antiplasmodial activity. Conclusion These findings suggest that the combination of stem bark extracts of T. macroptera and E. sigmoidea may have antimalarial activity. Additional in vivo antimalarial and toxicity studies are required for the scientific validation of the application of the two plant extracts in combination for antimalarial activity. The investigation of T. macroptera and E. sigmoidea via their interactions with proteins supported our hypothesis that the active substance is a strong inhibitor of the Plasmodium falciparum dihydrofolate reductase‐thymidylate synthase ( Pf ‐DHFR‐TS). Analyzing these compounds′ ADME characteristics contributes to the possibility of these ligands being developed into pharmaceutical forms.
Sandra et al. (Thu,) studied this question.
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