Study on the Therapeutic Effect and Mechanism of Gu Pi Sheng Ji Hua Zhuo Jie Du Decoction in Inducing Remission of Crohn’s Disease

Jiaming He, Zhibin Huang, Jie Zheng, Xu Deng, Minghui Wu, Gang Liu, Shuilin Chen, Yan Chen Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of ChinaCorrespondence: Yan Chen, Email [email protected]: To investigate the therapeutic effects of Gupishengji-Huazhuojiedu Decoction (GHD) in inducing remission in Crohn’s disease (CD) and to explore its potential underlying mechanisms.Methods: A two-stage exploratory study was conducted. Stage one included a retrospective analysis (17 GHD, 27 infliximab [IFX]) and a prospective single-arm trial (n=8), assessing clinical remission (CDAI < 150), endoscopic response (≥ 50% SES-CD reduction), and inflammatory biomarkers (CRP, fecal calprotectin). Stage two applied network pharmacology, machine learning (random forest, LASSO, XGBoost), and immunohistochemistry to explore GHD mechanisms.Results: In the retrospective analysis, the GHD group exhibited a higher clinical remission rate than the IFX group (88.2% vs 51.9%, p=0.01), with trends toward higher clinical response (88.2% vs 63.0%, p=0.07) and endoscopic remission rates (58.8% vs 37.0%, p=0.16). In the prospective study, 87.5% (7/8) of patients achieved both clinical remission and endoscopic response after 12 weeks of treatment. CDAI, SES-CD, CRP, and fecal calprotectin levels were all significantly reduced compared with baseline (p< 0.05). Bioinformatics analysis identified 13 key functional components (KFCGs) from GHD, and intersection of their 369 targets with CD differentially expressed genes yielded 36 candidate genes. Machine learning further prioritized six feature genes (IDO1, PRKG2, TGM2, ALDH1A2, ACPP, CASP1). Immune infiltration analysis revealed differences in immune cell populations between CD patients and healthy controls. Immunofluorescence experiments confirmed that GHD treatment significantly reduced the expression of CASP1, IDO1, CD11c, CD83, KLRG1, and CD45RO in intestinal mucosal tissue (p< 0.05).Conclusion: This study suggests that GHD may induce remission in CD through a multi-component, multi-target mechanism, particularly by modulating pathways related to CASP1 and IDO1, thereby improving clinical symptoms and endoscopic findings. The underlying mechanism may involve regulation of the intestinal immune-inflammatory microenvironment. GHD holds promise as a potential traditional Chinese medicine strategy for treating CD, but further validation in larger randomized controlled trials is warranted.Keywords: Crohn’s disease, chronic inflammatory disease, gastrointestinal tract, pharmacological therapies, traditional Chinese medicine