Network analysis and experimental verification of Schisandrin B reduces intestinal ischemia reperfusion injury
10.12092/j.issn.1009-2501.2023.02.004
- Author:
Xiaoyu HOU
1
;
Yufang LENG
1
;
Xuefen CAO
1
;
Xingjiao LV
1
;
Xiaoxia HAN
1
;
Janvier NIBARUTA
1
;
Yongqiang LIU
1
;
Yufang LENG
2
;
Yongqiang LIU
2
Author Information
1. The First Clinical Medical College of Lanzhou University
2. Department of Anesthesiology, First Hospital of Lanzhou University
- Publication Type:Journal Article
- Keywords:
apoptosis;
intestinal ischemia reperfusion injury;
network pharmacology;
Nrf2/HO-1 pathway;
Schisandrin B
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2023;28(2):147-154
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To explore schisandrin B (Sch B) pretreatment reduces intestinal ischemia reperfusion injury (IIRI) through inhibiting apoptosis by activation of Nrf2/HO-1 signing pathway in mice by network pharmacology and in vivo experiment. METHODS: (1) The targets of Sch B and IIRI were searched from online databases, Drawing Venn diagram to obtain the common target of them. Cytoscape software was imported to construct the protein-protein interaction (PPI) network to establish the "Drugs-Disease-core target gene" network. The mechanism of Sch B against IIRI was predicted through GO and KEGG enrichment analysis. (2) Thirty-six C57BL/6J mice were randomly divided into six groups (n = 6). The model of IIRI was established in four groups except the sham operation group. Three of the groups were pretreated with Sch B, Nrf2 inhibitor ML385, and Sch B + ML385, respectively. After the experiment, intestinal tissue samples were taken for HE staining, Chiu ' s score, apoptosis staining, immunohistochemistry (IHC), and immunoblotting (Western blot). RESULTS: A total of 412 Sch B related tar- gets, 2 166 IIRI related targets and 153 common targets were screened out through network pharmacology. There were 88 "Sch B-IIRI-core target gene" included NFE2L2 (Nrf2), HMOX1 (HO-1), BCL2, CASP3 (caspase 3), and so on. KEGG enrichment analysis screened 163 related pathways, apoptosis pathway ranked high showing that the pathway may play a key role in the treatment of IIRI by Sch B. The animal experiment had shown that Sch B reduced the Chiu's score and apoptotic while upregulating Nrf2, HO-1, Bcl-2 protein expression levels and Bcl-2/Bax, downregulating Bax, and cleaved caspase-3 expression levels, thereby reducing IIRI in mice, and that Nrf2 inhibitor ML385 reversed this process (P < 0.05). CONCLUSION: This study reveals that Sch B has the characteristics of multi-target and multi-pathway in the reduction of IIRI, and Sch B can reduce IIRI through inhibiting apoptosis by activation of Nrf2/ HO-1 pathway.
