Deciphering Emodin as an Antimalarial Lead Through Integrated Molecular Modeling and Experimental Validation

Background: Malaria remains a major global health burden, further exacerbated by the rapid emergence of Plasmodium strains resistant to frontline antimalarial therapies. This has necessitated the search for alternative sources of therapy. Methods: Here, we demonstrated the antiplasmodial potential of emodin through an integrated computational and experimental approach. Emodin was retrieved from the PubChem database and subjected to molecular docking against key P. falciparum regulatory and metabolic enzymes PfCDPK1, PfCDPK2, PfCDPK4, PfHK, and PfLDH. Results: Emodin demonstrated strong predicted binding affinities, with docking scores of −8.061, −8.017, and −5.021 kcal/mol against PfCDPK2, PfCDPK4, and PfHK, respectively—values surpassing those of established reference inhibitors. ADME and toxicity profiling further supported the drug-like physicochemical properties and acceptable safety margins of emodin. In vivo evaluation using P. berghei-infected mice revealed that emodin reduced parasitemia by up to 85.9% and significantly restored hematological and oxidative stress parameters, including PCV, GSH, total protein, and MDA levels. Conclusions: Collectively, these findings support emodin as a computationally predicted antiplasmodial scaffold with a proposed mechanism that remains hypothetical pending biochemical and cell-based validation. Its favorable predicted pharmacological profile and in vivo efficacy underscore its promise for further preclinical optimization.