In vivo and In silico evaluation of Gongronema latifolium as an antimalarial agent: Mechanisms of oxidative stress reduction and protein modulation

Abstract

Malaria remains a significant global health challenge, particularly in Sub-Saharan Africa, Asia, and parts of the Americas, with increasing resistance of Plasmodium falciparum to frontline antimalarial drugs exacerbating the issue. This study investigates the antimalarial potential of Gongronema latifolium (Benth), a medicinal plant native to Africa, known for its reported hypolipidemic, antioxidative, and anti-inflammatory properties. Despite the growing resistance to conventional treatments, Gongronema latifolium has not been extensively studied for its effects on malaria, particularly in relation to oxidative stress and parasite protein modulation. Phytochemical analyses revealed bioactive compounds, including alkaloids, saponins, and phenolics, which are likely responsible for its therapeutic effects. Using a Plasmodium berghei-infected Wistar rat model, the plant extract demonstrated dosedependent antioxidative effects, significantly increasing catalase (50%) and superoxide dismutase (75%) activity, thus reducing oxidative stress. In parallel, in silico studies identified strong interactions between the plant's phytocompounds and key malariaassociated proteins: Falcipain-2, Plasmodium falciparum lactate dehydrogenase (PfLDH), Plasmodium falciparum dihydrofolate reductase (PfDHFR), and Enoyl-ACP Reductase (PfENR). Docking computations and binding-free energy analyses revealed strong affinities, with Baicalin, Isoquercetin, Rutin, and Epicatechin-3-gallate registering the highest binding scores of - 10.731kcal/mol, -7.966kcal/mol, -12.114kcal/mol, -13.065kcal/mol for PfDHFR, Falcipain-2, PfLDH, and, PfENR respectively, suggesting potential inhibition of these proteins critical to parasite survival and replication. These findings indicate that Gongronema latifolium shows potential as an adjunct to existing antimalarial treatments, though further studies are needed to isolate and validate the efficacy of its active compounds.