Protective Effect of Qingchang Wenzhong Decoction on Colitis and Colitis-Related Carcinogenesis by Regulating Inflammation and Intestinal Fibrosis

Abstract

Yuan Cheng,1,2 Junxiang Li,1 Xiaosi Zhang,1 Yalan Li,3 Xiaojun Shi,1 Rui Shi,1 Tangyou Mao,1 Fushun Kou,1,4 Lei Shi1 1Gastroenterology Department, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, People’s Republic of China; 2School of Traditional Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210046, People’s Republic of China; 3School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 4Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of ChinaCorrespondence: Lei Shi, Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, No. 6, 1st Section, Fangxingyuan, Fangzhuang, Fengtai District, Beijing, 100078, People’s Republic of China, Email [email protected] Fushun Kou, Center for IBD Research, Department of Gastroenterology, The Shanghai Tenth People’s Hospital, Tongji University, No. 301 Yanchang Road, Shanghai, 200072, People’s Republic of China, Email [email protected]: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation, which may develop into ulcerative colitis-associated carcinogenesis (UCAC) with disease progression. Qingchang Wenzhong Decoction (QCWZD) is a classic and effective prescription for the clinical treatment of UC. QCWZD has been shown to alleviate intestinal mucosal injury in acute and chronic UC models. This study aimed to explore and then verify the pharmacological mechanisms of QCWZD in UC and UCAC therapy.Methods: In this study, approaches including microarray analysis, network pharmacology, and biological verification are employed to clarify the mechanism of QCWZD in the treatment of UC and UCAC. TCMSP, Swiss Target Prediction, and Similarity Ensemble Approach were used to investigate the active ingredients and targets of QCWZD. UC and UCAC valid targets were identified by the microarray data in the GEO database (GSE38713 and GSE47908). The core targets were obtained by PPI network and enriched by GO and KEGG. DSS and AOM/DSS mouse models were adopted to verify the above analysis results.Results: The enrichment analysis showed that the therapeutic targets of QCWZD enriched in blood circulation, cell adhesion molecules, and pathways of inflammation and cancer such as IL-17 signaling pathway and toll-like receptor signaling pathway were involved in the multiple synergies of QCWZD on UC and UCAC treatment. The results of experiments demonstrated that QCWZD can exert its effects on protecting the intestinal mucosal barrier, regulating inflammation and improving intestinal fibrosis in UC and UCAC and the main mechanism of QCWZD in treatment of UC and UCAC may be related to the activation of the IL-17, NF-κB and TLR4 signaling pathways.Conclusion: Our results indicated that QCWZD treated UC and UCAC via multiple targets and pathways and the IL-17, NF-κB and TLR4 signaling pathways may be highly involved in this process.Keywords: QCWZD, ulcerative colitis, ulcerative colitis-associated carcinogenesis, colitis-associated cancer, intestinal fibrosis

Keywords

• qcwzd
• ulcerative colitis
• ulcerative colitis-associated carcinogenesis
• colitis-associated cancer
• intestinal fibrosis.