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

doi:10.1007/s13659-026-00602-6

Natural Products and Bioprospecting ›› 2026, Vol. 16 ›› Issue (3): 45-45.DOI: 10.1007/s13659-026-00602-6

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

Hidayat Ullah^1,2, Huanli Cui^1,2,3,4, Yu Li^1,2,3, Binghuang Ye^1,2, Weijie Peng⁵, Yongdui Ruan^1,2,3,4, Weibo Dai⁵, Chunling Ma^1,2, Xianjing Hu^1,2,3,4

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

Received:2025-11-26 Online:2026-06-24
Contact: Weibo Dai,E-mail:daiweibo007@163.com;Chunling Ma,E-mail:yxba20@163.com;Xianjing Hu,E-mail:huxj2003@163.com
Supported by:
State Key Laboratory of Pathogenesis,Prevention,Treatment of Central Asian High Incidence Diseases Fund,SKL-HIDCA-2025-GD1,SKL-HIDCA-2025-GD2,Natural Science Foundation of Guangdong Province, 2023A1515011116,Dongguan Science and Technology of Social Development Program,20,231,800,939,832,Student Innovation Research and Entrepreneurship Training of Guangdong Medical University, GDMUCX2024214, GDMUCX2024168,Guangdong Medical University Undergraduate Innovation and Entrepreneurship Education Base Project, JDXM2024187,JDXM2024067F, Key Laboratory Construction Project of Dongguan Science and Technology Plan,20,231,600,401,471,20,241,600,403,291, Special Project for Clinical and Basic Sci & Tech Innovation of Guangdong Medical University, 4SG25302G、GDMULCJC2025132.

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

Hidayat Ullah^1,2, Huanli Cui^1,2,3,4, Yu Li^1,2,3, Binghuang Ye^1,2, Weijie Peng⁵, Yongdui Ruan^1,2,3,4, Weibo Dai⁵, Chunling Ma^1,2, Xianjing Hu^1,2,3,4

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

通讯作者: Weibo Dai,E-mail:daiweibo007@163.com;Chunling Ma,E-mail:yxba20@163.com;Xianjing Hu,E-mail:huxj2003@163.com
基金资助:
State Key Laboratory of Pathogenesis,Prevention,Treatment of Central Asian High Incidence Diseases Fund,SKL-HIDCA-2025-GD1,SKL-HIDCA-2025-GD2,Natural Science Foundation of Guangdong Province, 2023A1515011116,Dongguan Science and Technology of Social Development Program,20,231,800,939,832,Student Innovation Research and Entrepreneurship Training of Guangdong Medical University, GDMUCX2024214, GDMUCX2024168,Guangdong Medical University Undergraduate Innovation and Entrepreneurship Education Base Project, JDXM2024187,JDXM2024067F, Key Laboratory Construction Project of Dongguan Science and Technology Plan,20,231,600,401,471,20,241,600,403,291, Special Project for Clinical and Basic Sci & Tech Innovation of Guangdong Medical University, 4SG25302G、GDMULCJC2025132.

Abstract

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.

Key words: Ardisiacrispin B, Colitis-associated cancer, Gut microbiota, Apoptosis, JAK2/STAT3 signaling, AOM/DSS

摘要： 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.

关键词: Ardisiacrispin B, Colitis-associated cancer, Gut microbiota, Apoptosis, JAK2/STAT3 signaling, AOM/DSS

Hidayat Ullah, Huanli Cui, Yu Li, Binghuang Ye, Weijie Peng, Yongdui Ruan, Weibo Dai, Chunling Ma, Xianjing Hu. Natural triterpenoid Ardisiacrispin B attenuates colitis-associated cancer via JAK2/STAT3 pathway and gut microbiota modulation[J]. Natural Products and Bioprospecting, 2026, 16(3): 45-45.

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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

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