Targeting the Wnt/β-catenin pathway in inflammatory bowel disease: Mechanisms and challenges of traditional Chinese medicine treatment

Table 1 Summary of traditional Chinese medicine interventions targeting the Wnt/β-catenin pathway in experimental inflammatory bowel disease models

TCM intervention	Experimental model	Specific molecular targets on Wnt/β-catenin pathway	Biological effects on IBD
Huangqin-tang (herbal formula)	DSS-induced colitis mice	↓ β-catenin protein expression (colon tissue)	Reduced DAI, increased colon length, decreased IEC apoptosis
ZKC (herbal formula)	DSS-induced colitis mice	↓ MyD88/TLR4 → downstream suppression of Wnt pathway (indirect)	↓ Pro-inflammatory cytokines, ↓ oxidative stress, attenuated crypt loss and submucosal edema
Indigo Naturalis (single herbal extract)	DSS-induced colitis mice	↓ β-catenin expression in colon tissue; ↓ STAT1/STAT3 signaling	Suppressed Th1/Th17 responses, ↓ IFN-γ and IL-17, reduced oxidative stress
DIREN (herbal formula)	DSS-induced UC mice	↓ β-catenin, ↓ N-cadherin, ↓ integrin A1; inhibition of focal adhesion pathway	Attenuated colonic fibrosis, ↓ collagen deposition, ↓ apoptosis, ↑ BCL2
NGR1 (single compound)	DSS-induced colitis mice	↑ Wnt/β-catenin activation, ↑ Lgr5+ ISC proliferation	Promoted intestinal epithelial renewal, mucosal repair (reversed by Wnt inhibitors)
Acupuncture (manual)	DSS-induced UC rats	Modulation of NF-κB (downstream of Wnt) and inflammatory genes (genome-wide regulation)	Improved mucosal healing, reduced bleeding, ↓ lymphocyte/plasma cell infiltration
Electroacupuncture	DSS-induced UC rats; laparoscopic colorectal surgery (clinical)	Not fully defined, but regulates Wnt/NF-κB signaling axis	Reduced postoperative ileus, shorter hospital stay, enhanced bowel function recovery
Herbs-partitioned moxibustion (at RN12, ST25, RN6)	DSS-induced UC rats; UC patients (case study)	↓ β-catenin nuclear translocation (inferred from pathology)	Mucosal healing, reduced Mayo score, improved immune dysfunction, sustained remission
Moxibustion + acupuncture	DSS-induced UC rats; Active Crohn’s disease patients (RCT)	Regulation of downstream inflammatory effectors (NF-κB, cytokines) via Wnt pathway	↓ CDAI scores, improved quality of life, reduced endoscopic inflammation

TCM: Traditional Chinese medicine; IBD: Inflammatory bowel disease; DSS: Dextran sulfate sodium; DAI: Disease activity index; ZKC: Zhikang capsule; TLR4: Toll-like receptor 4; IFN: Interferon; IL: Interleukin; UC: Ulcerative colitis; NGR1: Notoginsenoside R1; ISC: Intestinal stem cell; NF-κB: Nuclear factor kappa B; RCT: Randomized clinical trial; CDAI: Crohn's Disease Activity Index; IEC: Intestinal epithelial cells.