Abstract
Snakebite envenomations pose significant global health challenges with limited effective treatments available. The complex physiological manifestations induced by snake venoms, such as hypoxia, vasoconstriction, and pain, have not fully deciphered at the genetic level. This study employs network pharmacology combined with gene expression analysis to uncover the molecular mechanisms underlying these interventions, and to explore nitric oxide as potential therapeutic target for snakebites. We used NCBI and GeneCards databases to collect the gene expression profile and therapeutic targets for snake bites. We identified that upregulation of genes like HIF1A and HIF3A, and downregulation of EGFA indicate responses to venom induced hypoxia. Change in expression of phospholipases and KNG1 suggests alteration in mechanisms involved in vasoconstriction. The increase in expression of cytokines and PTGS2 potentially linked to inflammation and pain induction. We identified 100 nitric oxide-related genes in mouse including 20 key genes directly involved in these responses to envenomation. The protein-protein interaction analysis through Cytoscape indicates that nitric oxide could play pivotal role in neutralizing venom effects. We identified MAFK as master regulator in nitric oxide associated genes set. Our observations highlight a previously unrecognized patterns of gene expression linked to hypoxia, vasoconstriction, and pain, and lays the groundwork for innovative approaches for treating snakebites.