Study on anti-inflammatory effect of taurolithocholic acid based on network pharmacology and its mechanism
10.3969/j.issn.1001-1978.2021.11.023
- Author:
Miao-Ran WANG
1
;
Yue LI
1
;
Ying ZHONG
1
;
Chun-Xiu CHEN
1
;
Ji-Bin LI
1
;
Miao-Ran WANG
2
;
Yue LI
2
;
Yun-Qi ZHANG
2
;
Xiao-Jing LIN
2
;
Ying ZHONG
2
;
Chun-Xiu CHEN
2
;
Xiao-Qiu XIAO
2
;
Yong ZHOU
3
Author Information
1. Dept of Nutrition and Food Hygiene, Chongqing Medical University
2. The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University
3. Dept of Clinical Nutrition, People' s Hospital of Chongqing Banan District
- Publication Type:Journal Article
- Keywords:
inflammatory response;
multiple targets;
network pharmacology;
RAW264.7 cells;
taurolithocholic acid;
TGR5
- From:
Chinese Pharmacological Bulletin
2021;37(11):1614-1619
- CountryChina
- Language:Chinese
-
Abstract:
Aim To explore the anti-inflammatory effect of taurolithocholic acid (TLCA) through network pharmacology-based analyses, to verify with in vitro macrophage study and to reveal the possible mechanisms. Methods The potential targets of TLCA were acquired from public database, and then the protein-protein interaction (PPI) networks against inflammation were constructed and visualized by using Cytoscape. Gene ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed. The binding activity of TLCA and its target (TGR5) was evaluated through molecular docking analysis. Lastly, the results of the network analysis were confirmed by lipopolysaccharide and interferon-γ induced RAW264.7 cells. Results There were 87 anti-inflammatory potential targets were screened. GO analysis revealed gene functions were mainly involved in regulation of inflammatory response, membrane raft and protein tyrosine kinase. The results of KEGG pathway analysis suggested that PI3K-Akt signaling pathway, human cytomegalovirus infection might be the critical pathways of TLCA against inflammation. The results of in vitro experiments showed that TLCA decreased the LPS and IFN-γ induced inflammatory response in RAW 264.7 macrophages. Furthermore, the expression of TGR5 protein increased after TLCA treatment. Conclusions The potential therapeutic targets of TLCA against inflammation are revealed through network pharmacology analysis. Our results indicate that TLCA might regulate key inflammatory markers through the membrane receptor TGR5.
