Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis

Xintian Shou; Yumeng Wang; Xuesong Zhang; Yanju Zhang; Yan Yang; Chenglin Duan; Yihan Yang; Qiulei Jia; Guozhen Yuan; Jingjing Shi; Shuqing Shi; Hanming Cui; Yuanhui Hu

doi:10.3389/fphar.2022.727608

Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis

Front Pharmacol. 2022 Feb 8:13:727608. doi: 10.3389/fphar.2022.727608. eCollection 2022.

Authors

Xintian Shou^{1

2}, Yumeng Wang², Xuesong Zhang¹, Yanju Zhang³, Yan Yang³, Chenglin Duan^{1

2}, Yihan Yang^{1

2}, Qiulei Jia^{1

2}, Guozhen Yuan¹, Jingjing Shi¹, Shuqing Shi^{1

2}, Hanming Cui¹, Yuanhui Hu¹

Affiliations

¹ China Academy of Chinese Medical Sciences Guang'anmen Hospital, Beijing, China.
² Beijing University of Chinese Medicine, Beijing, China.
³ National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Abstract

Ulcerative colitis (UC) is a disease with complex pathological mechanisms. We explored the potential molecular mechanisms behind the therapeutic functions of Qingzi Zhitong decoction (QZZTD) in the treatment of UC by network pharmacology and molecular docking. QZZTD is a formula of Chinese traditional medicine consisting of 10 herbs. The potential active ingredients of QZZTD and their target genes were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and UC-related target genes were obtained from GeneCards and OMIM databases. A total of 138 co-identified target genes were obtained by plotting the intersection target Venn diagram, and then the STRING database and Cytoscape software were used to establish protein-protein interaction networks and herb-ingredient-target networks. Four key active compounds and nine key proteins were identified. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the biological functions of potential target genes were associated with DNA transcription, signaling receptor and ligand activity, cytokine activity, cellular autophagy, and antioxidant pathways, with related pathways involving the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, advanced glycosylation end product (AGE)-RAGE signaling pathway, tumor necrosis factor (TNF) signaling pathway, and IL-17 signaling pathway. Moreover, the binding activities of key target genes and essential active compounds of Chinese herbal medicines in QZZTD were further validated by molecular docking. This demonstrated that quercetin, luteolin, hyndarin, and beta-sitosterol had good binding to eight key proteins, and Akt1 was the target protein with the best binding activity, suggesting that Akt1 could be the essential mediator responsible for signaling transduction after QZZTD administration. The rat experiment verified that QZZTD inhibited PI3K-Akt pathway activation and reduced inflammation in UC. In conclusion, our study suggested four potential key active components, including quercetin, were identified in QZZTD, which could interact with Akt1 and modulate the activation of the PI3K-Akt pathway. The other three pathways may also be involved in the signaling transduction induced by QZZTD in the treatment of UC.

Keywords: Qingzi Zhitong Decoction; molecular docking; molecular mechanism; network pharmacology; ulcerative colitis.