Therapeutic Effect of Smilax glabra Roxb. on Weaning Rats Against Pb-Induced Nephrotoxicity Based on Network Pharmacology.

Abstract

Lead (Pb) is a major environmental pollutant that can cause nephrotoxicity, hepatotoxicity, encephalopathy, and even death. Smilax glabra Roxb. has been used to treat heavy metal poisoning in China for over 500 years. We hypothesized that the Smilax glabra flavonoid extract (SGF) can ameliorate lead poisoning and investigated the possible mechanisms using network pharmacology. In total, 13 active compounds of Smilax glabra Roxb. and 71 overlapping potential targets were identified. The drug-compound-target-disease network analysis revealed that oxidative stress, inflammation, and apoptosis were mainly involved in the treatment of lead poisoning. Gene Ontology (GO) enrichment analysis showed that the biological processes involved in the therapeutic effect of Smilax glabra Roxb. against lead poisoning included biological processes, cellular components, and molecular functions. Additionally, 112 Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathways were obtained with the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways showing strong associations with lead poisoning by KEGG enrichment. The results of target pathway analysis showed that NF-κB was the most relevant gene involved in the therapeutic effect of Smilax glabra Roxb. against lead poisoning and was closely related to the MAPK signaling pathway. In vivo experiments confirmed that SGF treatment alleviated the pathological damage caused by lead-induced nephrotoxicity in weaning rats. Furthermore, SGF treatment markedly inhibited the expression of key proteins involved in the NF-κB/MAPK signaling pathway, highlighting the strong therapeutic effect of SGF against lead-induced nephrotoxicity. Results from network pharmacology and experimental verification indicated that SGF mitigated Pb-induced nephrotoxicity by downregulating the NF-κB/MAPK signaling pathway.