HRAMS Proteomics Insights on the Anti-Filarial Effect of Ocimum sanctum: Implications in Phytochemical-Based Drug-Targeting and Designing.

Lymphatic filariasis (LF) continues to impact 657 million individuals worldwide, resulting in lifelong and chronic impairment. The prevalent anti-filarial medications-DEC, albendazole, and ivermectin-exhibit limited adulticidal efficacy. Despite ongoing LF eradication programs, novel therapeutic strategies are essential for effective control. This study examines the mechanism of action of Ocimum sanctum on the filarial parasites Setaria cervi via a synergistic biochemical and proteomics methodology. The ethanolic extract of Ocimum sanctum (EOS) demonstrated potential anti-filarial action in the MTT reduction experiment, with an LC₅₀ value of 197.24 µg/mL. After EOS treatment, an elevation in lipid peroxidation (51.92%), protein carbonylation (48.99%), and NADPH oxidase (88.88%) activity, along with a reduction in glutathione (GSH) (-39.23%), glutathione reductase (GR) (-60.17%), and glutathione S transferase (GST) (-50.48%) activity, was observed. The 2D gel electrophoresis identified 20 decreased and 11 increased protein spots in the EOS-treated parasites relative to the control group. Additionally, in drug docking analysis, the EOS bioactive substances ursolic acid, rutin, and rosmarinic acid show a significant binding affinity with the principal differentially expressed proteins. This paper demonstrates, for the first time, that the anti-filarial efficacy of EOS is primarily facilitated by its impact on energy metabolism, antioxidant mechanisms, and stress response systems of the parasites.