Drug Design, Development and Therapy (Jul 2024)
Therapeutic Effects of Qingchang Tongluo Decoction on Intestinal Fibrosis in Crohn’s Disease: Network Pharmacology, Molecular Docking and Experiment Validation
Abstract
Yanan Li,1,2,* Jingyi Hu,1,2,* Ryan Au,1– 3 Cheng Cheng,1,2 Feng Xu,1,2 Weiyang Li,1,2 Yuguang Wu,1,2 Yuan Cui,1,2 Lei Zhu,1,2 Hong Shen1,2 1Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Jiangsu Provincial Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 3Academy of Chinese Culture and Health Sciences, Oakland, CA, 94612, USA*These authors contributed equally to this workCorrespondence: Hong Shen; Lei Zhu, Jiangsu Provincial Hospital of Chinese Medicine (Affiliated Hospital of Nanjing University of Chinese Medicine), 155 Hanzhong Road, Qinhuai District, Nanjing, Jiangsu Province, People’s Republic of China, Tel\Fax +86-025- 86617141, Email [email protected]; [email protected]: Qingchang Tongluo Decoction (QTF) is clinically used for the treatment of intestinal fibrosis in Crohn’s Disease (CD). However, the role of QTF in CD-associated fibrosis and its potential pharmacological mechanism remains unclear.Purpose: The objective of this study was to elucidate the potential mechanism of QTF in treating CD-associated fibrosis, employing a combination of bioinformatics approaches — encompassing network pharmacology and molecular docking — complemented by experimental validation.Methods: To investigate the material basis and potential protective mechanism of QTF, a network pharmacology analysis was conducted. The core components and targets of QTF underwent molecular docking analysis to corroborate the findings obtained from network pharmacology. In vitro, a colon fibrotic model was established by stimulating IEC-6 cells with 10 ng/mL of transforming growth factor(TGF-β 1). In vivo, an intestinal fibrosis model was induced in BALB/c mice by TNBS. The role of QTF in inhibiting the TGF-β 1/Smad signaling pathway was investigated through RT-qPCR, Western blotting, immunohistochemistry staining, and immunofluorescence staining.Results: Network pharmacology analysis revealed that QTF could exert its protective effect. Bioinformatics analysis suggested that Flavone and Isoflavone might be the key components of the study. Additionally, AKT1, IL-6, TNF, and VEGFA were identified as potential therapeutic targets. Furthermore, experimental validation and molecular docking were employed to corroborate the results obtained from network pharmacology. RT-qPCR, Immunofluorescence, and Western blotting results demonstrated that QTF significantly improved colon function and inhibited pathological intestinal fibrosis in vivo and in vitro.Conclusion: Through the application of network pharmacology, molecular docking, and experimental validation, QTF could be confirmed to inhibit the proliferation of intestinal fibroblasts associated with CD and reduce the expression of Collagen I and VEGFA. This effect is achieved through the attenuation of ECM accumulation, primarily via the inhibition of the TGF-β 1/Smad signaling pathway. Keywords: Qingchang Tongluo Decoction, Crohn’s Disease, intestinal fibrosis, network pharmacology, Pharmacology
