This study investigated the antioxidant and antimalarial properties of leaf extracts of Setaria megaphylla, Ageratum conyzoides Linn, and Chromolaena odorata Linn, plants used in folkloric treatment of malaria. The plants were assessed for phenolic profile, antioxidant capacity and radical scavenging activities using standard methods. Single, binary and ternary combinations of the processed leaves were subjected to hot aqueous extraction, and evaluated for in vivo antiplasmodial efficacy against Plasmodium berghei NK 65 using Swiss albino mice. The plants’ total phenolic profile varied as S. megaphylla (Sm; 118.06 µg/ml) > C. odorata (Co; 116.58 µg/ml) > A. conyzoides (Ac; 73.01 µg/ml), with catechin, dihydrocytisine and tannin being the most abundant phenolics. Total antioxidant capacities (TAC) and reducing power potentials (RPP) of the plants increased with increase in extract concentrations with Sm showing highest TAC (1.49 ± 0.02 mgAAE/g) and RPP (0.47 ± 0.01 mgAAE/g) values. A similar trend was observed for the hydroxyl, nitric oxide and DPPH radicals scavenging potentials, showing dose-dependent increases in scavenging potentials but with no observed significant (p<0.05) differences in activities at the highest extract dose of 400 µg/ml. The in vivo antimalarial study demonstrated that the combination of A. conyzoides and S. megaphylla was the most effective, significantly reducing parasitemia without causing mortality in the mice. This research highlights the potential of S. megaphylla, A. conyzoides, and C. odorata, especially the combination of their extracts as source of effective anti-malarial agents, and further confirms the folkloric use of hot aqueous extracts of the plants in malaria treatment.
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