Lu XX, Li X, Tian HJ, Li XH. Targeting the Wnt/β-catenin pathway in inflammatory bowel disease: Mechanisms and challenges of traditional Chinese medicine treatment. World J Gastroenterol 2026; 32(44): 122250 [DOI: 10.3748/wjg.122250]
Corresponding Author of This Article
Xu-Hao Li, MD, Postdoc, School of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, No. 4655 University Road, Changqing District, Jinan 250355, Shandong Province, China. l1xuhao2022@163.com
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Integrative & Complementary Medicine
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review-article
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Lu XX, Li X, Tian HJ, Li XH. Targeting the Wnt/β-catenin pathway in inflammatory bowel disease: Mechanisms and challenges of traditional Chinese medicine treatment. World J Gastroenterol 2026; 32(44): 122250 [DOI: 10.3748/wjg.122250]
World J Gastroenterol. Nov 28, 2026; 32(44): 122250 Published online Nov 28, 2026. doi: 10.3748/wjg.122250
Targeting the Wnt/β-catenin pathway in inflammatory bowel disease: Mechanisms and challenges of traditional Chinese medicine treatment
Xiao-Xue Lu, Xuan Li, Hua-Jie Tian, Xu-Hao Li
Xiao-Xue Lu, Xu-Hao Li, School of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
Xuan Li, Hua-Jie Tian, General Surgery, Linyi Hospital of Traditional Chinese Medicine, Linyi 276003, Shandong Province, China
Co-first authors: Xiao-Xue Lu and Xuan Li.
Co-corresponding authors: Hua-Jie Tian and Xu-Hao Li.
Author contributions: Li X, Li XH and Lu XX contributed to writing - first draft preparation; Lu XX contributed to paper revision (original draft) and response to reviewers (drafting of point-by-point responses); Li XH and Tian HJ contributed to writing - review & editing, and response to reviewers (critical revision of response content); Tian HJ and Li XH contributed to visualization (preparation of new Figure 2 and revision of Figure 1); Li XX contributed to supervision; Tian HJ contributed to project management; Li X and Tian HJ contributed to funding acquisition. Lu XX, Li X, and Li XH contributed to data curation (preparation of new Table 1 and reference updating). All authors participated in the manuscript revision process, approved the final version, and agreed to the submission.
AI contribution statement: Portions of this manuscript were edited using artificial intelligence (AI) tools (DeepL) solely for language refinement, grammar correction, and sentence fluency improvement, under the full supervision and verification of the authors. No AI tools were used to generate scientific content, data, figures, tables, conclusions, or any original intellectual contributions. All authors assume full responsibility for the integrity, accuracy, and originality of the manuscript.
Conflict-of-interest statement: All authors declare that they have no conflicts of interest, including any financial, personal, or professional relationships that could inappropriately influence or bias the content of this manuscript. No funding or sponsorship has been received from any organization that might have an interest in the submitted work.
Corresponding author: Xu-Hao Li, MD, Postdoc, School of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, No. 4655 University Road, Changqing District, Jinan 250355, Shandong Province, China. l1xuhao2022@163.com
Received: April 14, 2026 Revised: May 12, 2026 Accepted: July 1, 2026 Published online: November 28, 2026 Processing time: 169 Days and 17.3 Hours
Abstract
The Wnt/β-catenin pathway is a key regulator of intestinal mucosal repair and immune modulation in inflammatory bowel disease (IBD). Traditional Chinese medicine (TCM), including herbal formulas and acupuncture, has been reported to target this pathway; however, the mechanistic basis and therapeutic challenges remain unclear. This minireview synthesizes findings from preclinical and clinical studies investigating the effects of TCM interventions (herbal formulas, single compounds, acupuncture, moxibustion) on the Wnt/β-catenin pathway in IBD models and patients. Approximately 90% of colorectal cancers exhibit Wnt pathway abnormalities, and IBD patients face a 2- to 5-fold higher risk of colorectal cancer. In IBD-associated colorectal cancer (CRC), β-catenin nuclear expression is significantly higher than in sporadic CRC. TCM interventions—such as Huangqin-tang, Notoginsenoside R1, Indigo Naturalis, and electroacupuncture—have been shown to modulate key Wnt components and promote mucosal repair while limiting fibrosis. However, moderate activation of the pathway aids healing, whereas overactivation may lead to fibrosis and cancer, presenting a major therapeutic challenge. The bidirectional nature of Wnt/β-catenin signaling—beneficial for repair but harmful when overactivated—presents a therapeutic challenge. TCM offers multi-component, multi-target advantages but faces obstacles in mechanistic elucidation. Future efforts should integrate network pharmacology, multi-omics, and real-world data to construct ‘component-target-pathway-disease’ networks, while emerging platforms such as Chinese herbal medicine-derived extracellular vesicle-like particles and spatiotemporal regulation strategies may enable precision targeting of Wnt signaling in IBD.
Core Tip: This minireview discusses the Wnt/β-catenin pathway in traditional Chinese medicine for treating inflammatory bowel disease. Based on literature, it analyzes the pathway as a common target for herbal compounds and acupuncture-moxibustion, offering insights into treatment mechanisms and efficacy optimization. Understanding this pathway is crucial for advancing traditional Chinese medicine modernization and achieving precise inflammatory bowel disease therapy.
