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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2023, Vol. 28 ›› Issue (2): 147-154.doi: 10.12092/j.issn.1009-2501.2023.02.004

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Network analysis and experimental verification of  Schisandrin B reduces intestinal ischemia reperfusion injury

HOU Xiaoyu1, LENG Yufang1,2, CAO Xuefen1, LV Xingjiao1, HAN Xiaoxia1, Janvier NIBARUTA1, LIU Yongqiang1,2     

  1. 1The First Clinical Medical College of  Lanzhou University, Lanzhou 730000, Gansu, China; 2Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou 730000, Gansu, China
  • Received:2022-08-17 Revised:2022-12-14 Online:2023-02-26 Published:2023-03-10

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 targets, 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.

Key words: network pharmacology, Schisandrin B, intestinal ischemia reperfusion injury, apoptosis, Nrf2/HO-1 pathway

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