Abstract
Introduction: Apart from lacking macrofilaricidal activity, the anti-filarial drugs DEC, albendazole and ivermectin are also often associated with several severe side-effects. Therefore, macrofilaricidal drugs which are non-toxic and have minimal side effects are needed as better treatment options.
Methods: An ethanol extract of Ocimum sanctum (EOS) leaves was prepared and its anti-filarial activity was investigated by a combined biochemical and proteomics approach. Equal size and number of adult Setaria cervi worms were exposed to EOS following which the anti-oxidant activities were estimated and proteomic profile was studied by two-dimensional electrophoresis. The differentially expressed proteins were subjected to drug docking against EOS bioactive compounds.
Results: The EOS significantly reduced the viability of adult female Setaria cervi after 6 hr of incubation at 37o C. An increase in lipid peroxidation (51.92 %), protein carbonylation (48.99%), and NADPH oxidase (88.88 %) activity and a decrease in the glutathione (GSH) (-39.23 %), glutathione reductase (GR) (-60.17 %), and glutathione S- transferase (GST) (-50.48 %) activity were observed after EOS treatment. There were alterations in the proteomic profile of EOS-treated S. cervi at 250 µg/ml concentration in comparison to the control group of S. cervi, and 2D gel electrophoresis revealed 20 downregulated and 11 upregulated protein spots in the treated parasites. Further, in drug docking analysis, EOS bioactive compounds eugenol, kaempferol, luteolin, rutin and rosmarinic acid showed high binding affinity with the major differentially expressed proteins.
Conclusion: Herein, we report for the first time that the anti-filarial activity of EOS is largely mediated by its impact on the anti-oxidant, energy metabolism and stress response systems of the filarial parasites.
