Prediction of the mechanisms of action of Zhibai Dihaung Granule in cisplatin-induced acute kidney injury: A network pharmacology study and experimental validation

知柏地黄颗粒在顺铂所致急性肾损伤中的作用机制预测:网络药理学研究及实验验证

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作者:Zhen Liu, Ye Xu, Xinming Bai, Lvqian Guo, Xinran Li, Junling Gao, Yuou Teng, Peng Yu

Aim of the study

We aimed to provide a basis for the curative effect of ZDG on acute kidney injury induced by cisplatin (CIAKI). Materials and

Conclusions

Our study showed that ZDG could prevent and treat CIAKI by inhibiting cell apoptosis and inflammation, which provided a new efficacy and clinical application for ZDG.

Methods

The active compounds and protein targets of ZDG, as well as the potential targets of the CIAKI were searched from the database. The protein-protein interaction (PPI) network diagram and the drug-compounds-targets-disease network were constructed. Enrichment analysis was performed by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the effect of ZDG on the prevention and treatment of CIAKI was experimentally validated in vivo and in vitro.

Results

From the database, we screened 22 active compounds of ZDG and 226 related targets. We obtained 498 gene targets related to CIAKI, among which 40 genes overlapped with ZDG-related targets. Go enrichment and KEGG analysis got 339 terms and 64 pathways, respectively. Based on the above study, we speculated that ZDG has the potential effect on treatment CIAKI, and the mechanism may be related to cell apoptosis and inflammation. The results in vitro experiments showed that ZDG reduced the cytotoxicity of cisplatin to HK-2 and 293T cells, but did not affect the antitumor effect of cisplatin. Moreover, in vivo experiments further proved that ZDG effectively controlled kidney damage caused by cisplatin in SD rats. The results showed that ZDG could regulate the expression of CASP3, p65 and MAPK pathway related proteins, suggesting that ZDG's prevention of CIAKI may be related to apoptosis and inflammatory response. Conclusions: Our study showed that ZDG could prevent and treat CIAKI by inhibiting cell apoptosis and inflammation, which provided a new efficacy and clinical application for ZDG.

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