2022, Vol. 26 ›› Issue (32): 5132-5142

Network pharmacology and proteomics analysis of Jiawei Xiaoyao San in the treatment of liver cancer complicated with depression in rats

Wen Xiaoyu, Sun Yuhao, Li Zhuoxian, Xu Lijing, Xia Meng   

Abstract: BACKGROUND: Previous research has shown that Jiawei Xiaoyao San can regulate the content of dopamine and 5-hydroxytryptamine in the hippocampus and significantly improve the pathological morphology of the liver and depression symptoms in rats with liver cancer complicated with depression. However, its pharmacological mechanism has not been fully elucidated.
OBJECTIVE: Through network pharmacological analysis and proteomic testing, to screen out the effective targets of Jiawei Xiaoyao San for treating liver cancer complicated with depression and to discuss the active components and possible mechanism of Jiawei Xiaoyao San in the treatment of liver cancer complicated with depression.
METHODS: Sprague-Dawley rat models of liver cancer complicated with depression were established and treated with Jiawei Xiaoyao San. Proteomics and network pharmacology analyses were performed to identify the targets for differentially expressed proteins in serum. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted for effective targets. Liver morphology was detected using hematoxylin-eosin staining. Depression-like behavioral changes were observed in the rat models. Enzyme-linked immunosorbent assay was used to determine the serum level of related targets.
RESULTS AND CONCLUSION: Three possible common protein targets were identified based on proteomic and network pharmacology analyses: glutathione transferase (GSTM1), 3-phosphoinositide dependent protein kinase 1 (PDK1), heat shock protein 90AB1 (HSP90AB1). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses found that these targets were directly involved in the negative regulation of neuronal apoptosis, PI3K-Akt signaling pathway, and prostate cancer molecular signaling pathway. Hematoxylin-eosin staining and behavioral tests showed that Jiawei Xiaoyao San improved liver damage and depression-like behaviors in rats. Results from the enzyme-linked immunosorbent assay revealed that GSTM1, PDK1, and HSP90AB1 had corrective effects after intervention with Jiawei Xiaoyao San. To conclude, Jiawei Xiaoyao San may correct depression-like behavior and improve liver morphology by regulating the expression of GSTM1, PDK1, and HSP90AB1 in rats with liver cancer complicated with depression.
Key words: network pharmacology, proteomics, Jiawei Xiaoyao San, liver cancer complicated with depression, protein target