The Mechanism Punicalagin Treatment on Inflammatory Bowel Disease Based on Network Pharmacology Analysis
- VernacularTitle:基于网络药理学研究安石榴苷治疗炎症性肠病的作用机制
- Author:
Xuwen MAO
1
,
2
;
Guliruoyi PAERHATI
;
Yongzheng ZHANG
;
Zeb AMIR
;
Lufeng CHENG
Author Information
- Keywords: Punicalagin; IBD; Network pharmacology; Molecular docking
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(7):2437-2449
- CountryChina
- Language:Chinese
- Abstract: Objective To predict the potential mechanism of Punicalagin in the treatment of Inflammatory bowel disease by network pharmacology.Methods The intersection genes of Punicalagin and IBD were obtained from the database,and PPI,GO and KEGG pathways were enriched and analyzed.Punicalagin and the target were verified by molecular docking.C57BL/6J mice were drunk dextran sulfate sodium to establish inflammatory enteritis model,and were given Punicalagin for 7 d of intervention.During the administration,signs of mice in each group were observed,daily disease activity index was calculated;Intestinal permeability test after administration;The colon tissue was stained with hematoxylin eosin to observe the pathological changes and calculate the histological damage score;Detection of tumor necrosis factor(TNF-α),Interleukin-10(IL-10),myeloperoxidase(MPO),chemokine 1(CXCL1)and other cytokines in colon tissue of mice by ELISA.Detection of TNF-α,IL-6,MPO and CXCL1 level in mouse serum by ELISA.CCK8 method was used to determine the effect of Punicalagin on the proliferation activity of caco-2 cells.The levels of cytokines released by caco-2 cells induced by lipopolysaccharide(LPS)were detected by ELISA.Results 14 common targets of Punicalagin and IBD were obtained,including tumor necrosis factor(TNF),arachidonic acid-5-lipoxygenase(ALOX5)and vascular endothelial growth factor A(VEGFA).KEGG enrichment analysis predicted that the treatment of IBD by Punicalagin mainly acted on arachidonic acid signaling pathway,age-rage signaling pathway,VEGR signaling pathway and Ras signaling pathway.Molecular docking showed that Punicalagin had good docking activity with TNF receptor.Compared with the model group,the decreasing range of body mass in Punicalagin group abated(P<0.01);the disease activity index of Punicalagin group decreased significantly(P<0.01);The congestion and edema of colonic mucosa were significantly reduced,and the histological injury score was significantly reduced(P<0.01);The level of TNF-α,IL-1β,MPO,CXCL1,IL-6,IL-18,IFN-γ in colon tissue was significantly decreased(P<0.01);20-300 μmol·L-1 Punicalagin promoted caco-2 cell proliferation and inhibited TNF-α secretion induced by LPS,up-regulation of IL-10 levels.Conclusion Punicalagin inhibits the secretion of TNF-α and other proinflammatory factors,up-regulation of the level of anti-inflammatory factor IL-10,and improvement of colonic inflammatory response in IBD mice.
