Mechanism of renal injury in rats induced by Phytolaccae Radix based on network toxicology / 中草药

ABSTRACT

Objective: Based on the strategy of network toxicology, the potential mechanism of renal injury in rats induced by Phytolaccae Radix was preliminarily explored. Methods: Firstly, by consulting the online database and mining the text, the chemical composition library of Phytolaccae Radix was established. The reverse molecular docking technology based on pharmacophores was performed to predict the relevant targets of chemical components and the target of nephrotoxicity induced by Phytolaccae Radix was obtained by intersecting with the target of nephrotoxicity. Potential substance basis of nephrotoxicity induced by Phytolaccae Radix was obtained by reverse analysis. Secondly, a large-scale protein-protein interactions were used to screen key targets, and key pathways for nephrotoxicity were analyzed by GO and KEGG biological annotation. Finally, a rat model of nephrotoxicity induced by esculentoside A was constructed and molecular biology methods were used to detect the expression of important targets in related pathways. Results: A total of 56 chemical components and 148 potential targets were obtained through literatures and related databases. Among them, 38 components, 34 targets, and 93 pathways were closely related to the generation of nephrotoxicity, mainly involving TNF signaling pathway, calcium signaling pathway, NF-κB signaling pathway, and VEGF signaling, thus participating in the beginning and end of nephrotoxicity events. Pathological results showed that the kidney tissues of rats were damaged to varying degrees after 7 d of treatment with esculentoside A. Western blot showed that the expression of IκBα was down-regulated (P < 0.01) and the expression of p-IκBα was up-regulated (P < 0.05). Quantitative detection of TNF-α and IL-1β by ELISA showed that both expressions were up-regulated (P < 0.05). Conclusion: Network toxicology can be used to preliminarily screen potential toxic substances. Esculentoside A based on network toxicology screening can induce nephrotoxicity in rats. Its molecular mechanism is related to activation of NF-κB signaling pathway and overexpression of inflammatory factors.