2. Academic Validation
  3. Natural triterpenoid Ardisiacrispin B attenuates colitis-associated cancer via JAK2/STAT3 pathway and gut microbiota modulation

Natural triterpenoid Ardisiacrispin B attenuates colitis-associated cancer via JAK2/STAT3 pathway and gut microbiota modulation

  • Nat Prod Bioprospect. 2026 Mar 11;16(1):45. doi: 10.1007/s13659-026-00602-6.
Hidayat Ullah # 1 2,  Huanli Cui # 1 2 3 4,  Yu Li 1 2 3,  Binghuang Ye 1 2,  Weijie Peng 5,  Yongdui Ruan 1 2 3 4,  Weibo Dai 6,  Chunling Ma 7 8,  Xianjing Hu 9 10 11 12
Affiliations

Affiliations

  • 1 Dongguan Key Laboratory of Fundamental Research and Clinical Application of Toxic Chinese Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, PR China.
  • 2 Dongguan Key Laboratory of TCM for Prevention and Treatment of Refractory Digestive Diseases, Guangdong Provincial Key Laboratory of Natural Drugs Research and Development, Guangdong Medical University, Dongguan, 523808, PR China.
  • 3 School of Pharmacy, Dongguan Branch, National Engineering Research Center for Modernization of Traditional Chinese Medicine, Dongguan, 523808, PR China.
  • 4 Department of Acupuncture, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523121, PR China.
  • 5 Pharmacology Laboratory, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 528401, PR China.
  • 6 Pharmacology Laboratory, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 528401, PR China. [email protected].
  • 7 Dongguan Key Laboratory of Fundamental Research and Clinical Application of Toxic Chinese Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, PR China. [email protected].
  • 8 Dongguan Key Laboratory of TCM for Prevention and Treatment of Refractory Digestive Diseases, Guangdong Provincial Key Laboratory of Natural Drugs Research and Development, Guangdong Medical University, Dongguan, 523808, PR China. [email protected].
  • 9 Dongguan Key Laboratory of Fundamental Research and Clinical Application of Toxic Chinese Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, PR China. [email protected].
  • 10 Dongguan Key Laboratory of TCM for Prevention and Treatment of Refractory Digestive Diseases, Guangdong Provincial Key Laboratory of Natural Drugs Research and Development, Guangdong Medical University, Dongguan, 523808, PR China. [email protected].
  • 11 School of Pharmacy, Dongguan Branch, National Engineering Research Center for Modernization of Traditional Chinese Medicine, Dongguan, 523808, PR China. [email protected].
  • 12 Department of Acupuncture, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523121, PR China. [email protected].
  • # Contributed equally.
PMID: 41807868 DOI: 10.1007/s13659-026-00602-6
Abstract

Colitis-associated Cancer (CAC) arises from persistent intestinal inflammation, immune dysregulation, and microbiota-driven epithelial injury, representing a major link between inflammatory bowel disease and colorectal malignancy. Despite advances in therapy, colon Cancer remains one of the leading causes of cancer-related mortality worldwide, underscoring the urgent need for effective preventive and immunomodulatory interventions. Ardisiacrispin B (AB), a bioactive triterpenoid isolated from the Ardisia genus, has been reported to suppress tumor growth by regulating Apoptosis and ferroptosis; however, its role in inflammation-driven colorectal tumorigenesis remains unexplored. In this study, we investigated the protective and antitumor effects of AB in an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CAC mouse model, with a focus on inflammatory signaling pathways, epithelial remodeling, and gut microbiota modulation. AB administration markedly alleviated disease severity, as evidenced by a significant reduction in disease activity index, including body weight loss, diarrhea, and rectal bleeding. Histopathological evaluation revealed preserved colonic mucosal architecture, diminished inflammatory cell infiltration, and a pronounced reduction in tumor number and size. AB treatment partially modulated the gut microbiota, with a trend toward enrichment of beneficial taxa and a reduction in inflammation-associated Bacterial populations. Concurrently, AB robustly downregulated the colonic expression of pro-inflammatory cytokines and chemokines. AB treatment was associated with increased expression of pro-apoptotic markers, indicative of enhanced apoptotic signaling in colonic epithelial cells, as indicated by increased expression of cleaved PARP, cleaved Caspase-3, p53, and Bax, while markedly inhibiting cellular proliferation through suppression of Ki-67. Mechanistically, AB was associated with attenuation of key inflammatory and oncogenic signaling pathways, including IL-6/JAK2/STAT3, LPS/TLR4/MyD88/NF-κB, and MAPK cascades. Collectively, Ardisiacrispin B attenuates colitis-associated Cancer by rebalancing gut microbiota, suppressing inflammation, and inducing tumor cell Apoptosis through inhibition of key oncogenic signaling pathways.

Keywords

AOM/DSS; Apoptosis; Ardisiacrispin B; Colitis-associated cancer; Gut microbiota; JAK2/STAT3 signaling.

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