Mechanism of regulating immune dysfunction of sepsis based on network pharmacology and experimental verification
- Author:
Shi-Fan YAN
1
;
Yi-Min ZHU
1
;
Shi-Fan YAN
2
;
Wen LIU
2
;
Xiao-Xiao GU
2
;
Xiao-Xiao JIANG
2
;
Fang CHEN
2
;
Yan-Juan LIU
2
;
Yi-Min ZHU
2
;
Ting YU
3
Author Information
- Publication Type:Journal Article
- Keywords: immunosuppression; inflammatory cytokines; molecular docking; network pharmacology; sepsis; Shengjiang Powder
- From: Chinese Pharmacological Bulletin 2023;39(9):1755-1764
- CountryChina
- Language:Chinese
- Abstract: Aim To verify the role of Shengjiang Powder in sepsis and explore its molecular mechanism. Methods The targets of drug active ingredients and disease-related targets were searched by TCMSP, Disgenet and other databases, and the intersection of the two was selected. DAVID database was used to carry out enrichment analysis of GO and KEGG pathways for intersection targets, and molecular docking was performed between drug active ingredients and core genes of key pathways. Mouse model of sepsis was constructed by cecal ligation puncture (CLP). Spleen tissue and serum of mice were collected. The percentage of T cell subsets in spleen was detected by flow cytometry, and IL-6 and IL-10 levels in serum were detected by ELISA. Results A total of 25 active ingredients, 238 targets of active ingredients, 2797 disease-related targets, 90 genes of intersection between active ingredients and disease-related targets, potential targets were AKT, JUN, EGFR, MMP9, etc. GO enrichment analysis showed 1021 items, including 942 biological processes, 23 cell compositions and 55 molecular functions. KEGG pathway analysis found that the intersection genes were mainly enriched in THE PD-1/PD-L1 signaling pathway, HIF-1 signaling pathway, TNF signaling pathway and inflammatory mediators signaling pathway, indicating that the therapeutic effect may be related to these pathways. The molecular docking results showed that quercetin, kamanol, emodin and other core compounds could be well combined with key genes. Flow cytometry results showed that after seven days of CLP, the proportion of CD4 T cells in spleen decreased, the proportion of CD4 PD-1 T cells increased, the release of IL-6 decreased, the content of IL-10 increased, and the mice were immunosuppressed. The percentage of CD4 T cells in spleen increased, the number of CD4 PD-1 T cells decreased, the release of IL-6 was enhanced, the content of IL-10 decreased, and the immunosuppression was improved. Conclusions It is proved that Shengjiang Powder can increase the release of pro-inflammatory cytokine IL-6, increase the ratio of CD4 T/CD8 T cells, and decrease the expression of anti-inflammatory cytokine IL-10 in the late stage of sepsis, so as to improve immune suppression in the late stage of sepsis and improve the survival rate of mice.
