Exploring the mechanism of cytisine in treating respiratory depression following venomous snake bites based on network pharmacology and molecular docking

Abstract

Objective: To investigate the antivenom mechanism of cytisine through network pharmacology and molecular docking (MD) techniques, with the intention of exploring its clinical applications. Methods: The cytisine target and the snakebite respiratory inhibition target were obtained using the Swiss Target Prediction platform and the Gene Cards database. The two target sets were overlapped to form a protein interaction network. Additionally, pathway enrichment analysis was conducted on cross targets, and the related pathways for the treatment of snake venom-induced respiratory failure were obtained. Verification of the MD between cytisine and its related targets was performed using the Autodock 1.5.7 software. The respiratory depression model of rats bitten by venomous snakes was established, and the expression of key target genes in the rat model was verified by western blot (WB). Result: A total of 16 targets of cytisine and 9 potential targets of cytisine in treating snake venom-induced respiratory depression were obtained. Core targets including CHRNA7, CHRNG, CHRNB1, CHRND, CHRNA1 and DRD2 were obtained. These targets are mainly enriched in neuroactive ligand-receptor interaction pathway and cholinergic synaptic pathway. The MD results demonstrated favorable docking activity of cytisine with its related targets. WB experiments showed that snake venom reduced the levels of CHRNA7 and CHRNG. Treatment with serum and cytisine could slow down this decline. Conclusion: Cytisine may synergistically target CHRNA7, CHRNG, CHRNB1, CHRND, CHRNA1, DRD2 and other proteins, modulating cholinergic and neuroactive pathways to alleviate neuromuscular block and protect acetylcholine receptors.