Mechanism of Poecilobdella Manillensis Lyophilized Powder on Hyperuricemia Based on Network Pharmacology, RNA-seq Technology and Experimental Validation
10.13748/j.cnki.issn1007-7693.20230100
- VernacularTitle:基于网络药理学和转录组学及实验验证探究菲牛蛭冻干粉抗高尿酸血症的作用机制
- Author:
Yunyi DONG
1
;
Yike LIU
1
;
Xiaolin DENG
1
;
Jian LIANG
1
Author Information
1. Medical College of Guangxi University, Nanning 530004, China
- Publication Type:Journal Article
- Keywords:
hyperuricemia ； Poecilobdella manillensis； network pharmacology ； RNA-seq
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(12):1671-1681
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To investigate the multi-target mechanism of action of Poecilobdella manillensis lyophilized powder(SZ) against hyperuricemia(HUA) based on network pharmacology and transcriptomics approaches, combined with animal experiments.
METHODS
Utilizing Symmap, SwissTargetPrediction, and Pharmmapper databases, the potential active components and corresponding targets of SZ were obtained. Through the Gene Cards and OMIM databases, HUA-related targets were obtained. By taking the intersection mapping, the common targets of SZ and HUA were identified. Cytoscape 3.9.0 software was used to construct a drug component-disease target interaction network, and in combination with the STRING database, a protein interaction network was built and core targets were screened. The DAVID database was used to perform GO biological function annotation and KEGG pathway enrichment analysis on the intersecting targets. A mouse model of HUA was constructed using potassium oxyzate combined with high purine diet, and the effects of SZ on these mice were examined using ELISA and biochemical index detection. qRT-PCR was used to validate the results of RNA-Seq and network pharmacology enrichment analysis.
RESULTS
Network pharmacological analysis identified 11 major bioactive substances in SZ and 72 potential targets involved in the treatment of hyperuricemia, involving multiple biological processes and different signaling pathways. It was shown that SZ significantly reduced serum uric acid, creatinine and urea nitrogen levels in hyperuricemic mice by inhibiting xanthineoxidase activity. SZ also reduced the levels of URAT1 while increasing the levels of ABCG2. RNA sequencing analysis revealed that there were 112, 536 and 107 differentially expressed genes in the model group vs treated group, control group vs model group and control group vs treated group, respectively. qRT-PCR results indicated that SZ downregulated the expression of genes related to Th17 cell differentiation as well as mRNA of genes on IL-17 and PI3K/Akt signaling pathways.
CONCLUSION
SZ has therapeutic effects on hyperuricemia. The mechanism of action maybe related to the inhibition of hepatic xanthineoxidase activity, down-regulation of URAT1 levels, up-regulation of ABCG2 levels, affecting the differentiation of Th17 cells and thus the IL-17 signaling pathway, thereby reducing the inflammatory response.
