Mechanism of treatment of Tibet yak-origin Salmonella infections by Tibetan medicine Terminalia Chebula via Bax/Bcl-2 and PTGS2/SLC3A2 pathway was analyzed based on network pharmacology and experimental validation
10.16303/j.cnki.1005-4545.2024.09.25
- VernacularTitle:基于网络药理学和试验验证分析藏药诃子通过Bax/Bcl-2和PTGS2/SLC3A2通路治疗西藏牦牛源沙门菌感染的机制
- Author:
Dengyu LI
1
;
Kaiqin ZHANG
;
Xiaofeng XUE
;
Zhanchun BAI
;
La YANG
;
Shaohui WANG
;
Jingjing QI
;
Sizhu SUOLANG
Author Information
1. 西藏农牧学院动物科学学院,西藏林芝 860000
- Keywords:
network pharmacology;
Terminalia Chebula;
enteritis;
molecular docking;
mechanism of action
- From:
Chinese Journal of Veterinary Science
2024;44(9):2040-2049
- CountryChina
- Language:Chinese
-
Abstract:
In order to understand the potential target and related mechanism of action of Termina-lia Chebula treatment,network pharmacology and molecular docking methods were used in this experiment,and the challenge test of Salmonella from yak was performed.The active ingredients and potential targets of Terminalia Chebula were screened through HERB cluster identification database,TCMSP database and SwissTargetPrediction web page tool,and"gastroenteritis"was searched through OMIM and GeneCards database.Cytoscape and STRING databases were used to construct the Terminalia Chebula PPI network to screen out key targets,the intersection targets between Terminalia Chebula and enteritis were obtained through Venny platform,and gene ontol-ogy(GO)and Kyoto encyclopedia database of genes and genomics(KEGG)were enriched through DAVID database.The core target of screening was verified by molecular docking.After that,the gastrointestinal inflammation model of mice was established,the pathological changes of gastroin-testinal tract were observed,and the effect of Terminalia Chebula on the target protein was veri-fied by Western blot test.The results showed that:after analyzing and sorting out 8 main active in-gredients of Terminalia Chebula,118 targets of Terminalia Chebula were screened,11 161 targets of gastroenteritis and 100 targets of intersection were obtained;the core targets of PTGS2,CASP3,SLC3A2,Bax,Bcl-2 and TP53 of Terminalia Chebula and enteritis were obtained through PPI network.GO and KEGG enrichment analysis collected 337 items and 138 items,respectively,mainly related to chemokine pathway,PI3K-Akt signaling pathway,apoptosis related pathway,i-ron ion transport related pathway,NF-κB signaling pathway,etc.The results of molecular docking showed that chebulidic acid,the first active component of chebulidic acid,can bind to Bax,Bcl-2,PTGS2 and SLC3A2 through hydrogen bonding,hydrophobic action,π-π packing force and other intermolecular forces.The pathological tissue sections showed that Terminalia Chebula could sig-nificantly recover gastrointestinal tissue injury.Western blot test results showed that Terminalia Chebula can regulate the process of apoptosis and iron death through Bax/Bcl-2 and PTGS2/SLC3A2 pathways to achieve the effect of treating intestinal inflammatory damage.The results showed that Terminalia Chebula can regulate the occurrence and development of enteritis by regu-lating apoptosis and iron death through Bax/Bcl-2 and PTGS2/SLC3A2 pathways.Terminalia Chebula has the characteristics of multi-target and multi-pathway in the treatment of enteritis.
