Network pharmacological prediction of the mechanism of action of Shen-Zhu-Lian-Bai Decoction in the treatment of ulcerative colitis

Abstract

The incidence of ulcerative colitis (UC) is on the rise globally. Shen-Zhu-Lian-Bai decoction (SZLBD) can relieve the clinical symptoms of UC. This study aimed to investigate the underlying molecular mechanism of SZLBD in the treatment of UC. The key treatment targets of SZLBD for UC were obtained based on the online database, and combined with the STRING database and Cytoscape 3.7.2 software, PPI network was constructed and visualized. The GEO database was utilized to validate the expression levels of core targets in UC. Metascape database GO functional annotation and KEGG pathway enrichment analysis. Molecular docking technology was used to verify the docking of core compounds with key targets. RT-qPCR and Western Blot were used to detect the expression of key targets in HCoEpiC cells for verification. After screening, 67 targets shared by SZLBD and UC were obtained. It is predicted that IL-6, IL-1B, and AKT1 might be the key targets of SZLBD in the treatment of UC. Quercetin was the main active ingredient. GEO results showed that the expression levels of IL-6, IL-1B and AKT1 were higher in the UC group compared to the control group. GO and KEGG analyses showed that these targets were related to apoptosis and inflammation. The results of molecular docking demonstrated that the AKT1 gene, a key target of quercetin, had the highest affinity of -9.2 kcal/mol. Cell experiments found that quercetin could affect the expression of IL-6, IL-1B, and AKT1. This study preliminarily explored and verified the mechanism of action of SZLBD in the treatment of UC, which provides a theoretical basis for subsequent in vivo mechanism studies.

Keywords: Cell experiments; Molecular docking; Network pharmacological; Shen-Zhu-Lian-Bai decoction (SZLBD); Ulcerative colitis.

Figure 1

Flow chart of SZLBD against UC.

Figure 2

Key active compounds of SZLBD-target network. The teal represents traditional Chinese medicines (HL, Huanglian; CP, Chenpi; BZ, Baizhu; HB, Huangbai; MCX, Machixian; BS, Baishao; DS, Dangshen), the pink represents active ingredients, and the blue represents the targets of SZLBD.

Figure 3

Common targets of SZLBD and UC. The red represents UC (ulcerative colitis), the teal represents traditional Chinese medicine (HL, Huanglian; CP, Chenpi; BZ, Baizhu; HB, Huangbai; MCX, Machixian; BS, Baishao; DS, Dangshen), the pink represents active ingredients, and the blue represents the targets of SZLBD acting on UC.

Figure 4

PPI network.

Figure 5

Expression of IL-6, IL-1B and AKT1 between normal and UC samples. **p < 0.01,****p < 0.001.

Figure 6

GO functional annotation and KEGG signaling pathway enrichment analysis results. (A) BP enrichment analysis; (B) CC enrichment analysis; (C) MF enrichment analysis (D) KEGG enrichment analysis.

Figure 7

Molecular docking of quercetin (MOL000098) with its targets. (A) IL-6 protein-quercetin; (B) IL-1B protein-quercetin; (C) AKT1 protein-quercetin.

Figure 8

Quercetin improves LPS-induced inflammatory damage of HCoEpiC cells. (A) The choice of LPS safety and effective concentration; (B) The choice of quercetin safety and effective concentration; (C) Levels of mRNA expression of IL-6; (D) Levels of mRNA expression of IL-1B; (E) Levels of mRNA expression of AKT1; (F–I) Expression of IL-6, IL-1B and AKT1 proteins. *p < 0.05,**p < 0.01,***p < 0.001.