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World J Gastroenterol. Dec 21, 2026; 32(47): 122777
Published online Dec 21, 2026. doi: 10.3748/wjg.122777
Ya-Han-Lu-Duan decoction reshapes tumor microenvironment to treat colitis-associated colorectal cancer by regulating arachidonic acid metabolism
Li-Fang Chen, Yuan-Yuan Chen, Fei-Tian Min, Wei-Bo Wen, Su-Feng Luo, Ya Luo, Qin-Rong Li, Zi-Qing Xu, Sha-Sha Liu, Xia Chen, Ning Wang, Huan-Tian Cui, Xiao-Rong Wang
Li-Fang Chen, Su-Feng Luo, Ya Luo, Qin-Rong Li, Department of Gastroenterology, Xishuangbanna Dai Autonomous Prefecture People’s Hospital, Jinghong 666100, Yunnan Province, China
Yuan-Yuan Chen, Zi-Qing Xu, Sha-Sha Liu, Xiao-Rong Wang, Department of Gastroenterology, Dai Medicine Hospital of Xishuangbanna Dai Autonomous Prefecture, Jinghong 666100, Yunnan Province, China
Fei-Tian Min, Wei-Bo Wen, Ning Wang, Huan-Tian Cui, The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming 650500, Yunnan Province, China
Xia Chen, Department of Spleen and Gastroenterology, Yunnan Provincial Hospital of Traditional Chinese Medicine, Kunming 650021, Yunnan Province, China
Co-first authors: Li-Fang Chen and Yuan-Yuan Chen.
Co-corresponding authors: Huan-Tian Cui and Xiao-Rong Wang.
Author contributions: Chen LF and Chen YY performed the research and wrote the original draft, contributed equally to this article as co-first authors; Chen LF and Cui HT acquired funding; Min FT, Wen WB and Luo SF developed methodology; Luo Y, Li QR and Xu ZQ performed the experiments, acquired and analyzed data; Li QR, Xu ZQ, Liu SS, Chen X and Wang N interpreted the data; Cui HT and Wang XR designed the research study, participated in review and editing, contributed equally to this article as co-corresponding authors; all authors approved the final version of the article.
AI contribution statement: The entirety or any portion of the main text of the manuscript was not AI-generated. The AI tool was not used for language polishing, translation, or writing assistance of the manuscript. The AI tool did not participate in design of the study or interpretation of its results. This study was designed by our team. No image in the manuscript was generated by AI.
Supported by 2025 Yunnan Provincial International Science and Technology Commissioner (Individual) Certification Program, No. 202503AK140045; and Open Research Fund Program of Yunnan Key Laboratory for Dai and Yi Medicines (Yunnan University of Chinese Medicine), No. 2025ZD2502.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethical Review Committee of Animal Experiments in Yunnan University of Chinese Medicine, No. YNUCM-XMSB-G-20250280.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data in the research will be made available on request.
Corresponding author: Huan-Tian Cui, PhD, Post Doctoral Researcher, Principal Investigator, Senior Researcher, The First School of Clinical Medicine, Yunnan University of Chinese Medi
cine, No. 1076 Yuhua Road, Chenggong District, Kunming 650500, Yunnan Province, China.
1762316411@qq.com
Received: April 28, 2026
Revised: June 16, 2026
Accepted: September 22, 2026
Published online: December 21, 2026
Processing time: 182 Days and 21.1 Hours
BACKGROUND
Ya-Han-Lu-Duan (YHLD) decoction is a classical Dai ethnic prescription widely used to treat intestinal inflammatory diseases. However, its ability to prevent colitis-associated colorectal cancer (CAC), the molecular mechanisms responsible, and the active constituents of the formulation remain unknown.
AIM
To elucidate YHLD’s therapeutic mechanisms against CAC, focusing on tumor microenvironment (TME).
METHODS
We evaluated YHLD in a mouse model of CAC induced by azoxymethane and dextran sulfate sodium. To elucidate mechanisms, we applied transcriptomic and untargeted metabolomic analyses to colon tissues from treated and control animals. Key pathways identified by these omics approaches were validated by enzyme-linked immunosorbent assay, western blot, and immunofluorescence. We characterized YHLD’s chemical constituents using UPLC-Q-TOF-MS, then performed molecular docking to model interactions between major components and enzymes in arachidonic acid (AA) metabolism, providing a preliminary screen for potential molecular targets.
RESULTS
YHLD significantly attenuated body weight loss and colon shortening in CAC mice, alleviated colonic histopathological injury, and reduced tumor formation. Transcriptomic analysis showed that genes differentially expressed after YHLD treatment were enriched in TME-related pathways, including Cytokine-cytokine receptor interaction and extracellular matrix-receptor interaction. YHLD decreased the expression of pro-inflammatory and pro-tumor growth factors and reduced markers of cancer-associated fibroblasts and myeloid-derived suppressor cells. Untargeted metabolomic analysis further identified AA metabolism as a pathway co-enriched in both transcriptomic and metabolomic datasets. Consistently, YHLD suppressed the expression of key AA metabolism enzymes, PTGS2 and ALOX12. In addition, major components of YHLD, including Pentahydroxybufostane, Clematoside B, Psammosilenin A and Dulcoside A, showed high binding affinity to PTGS2 and ALOX12, respectively, suggesting that YHLD may coordinately regulate AA metabolism through multiple active components.
CONCLUSION
This study provides the first evidence that YHLD exerts a significant protective effect against CAC. The underlying mechanism likely involves inhibition of ALOX12-mediated and PTGS2-mediated AA metabolism, suppression of cancer-associated fibroblast activation and myeloid-derived suppressor cells infiltration, and remodeling of the immunosuppressive TME, thereby alleviating CAC progression. These findings offer experimental and mechanistic support for the development of YHLD as a preventive agent for CAC.
Core Tip: Ya-Han-Lu-Duan (YHLD) decoction exerts a significant protective effect against colitis-associated colorectal cancer. YHLD remodels the immunosuppressive tumor microenvironment by suppressing cancer-associated fibroblast activation and myeloid-derived suppressor cells infiltration. YHLD is likely to inhibit ALOX12-mediated and PTGS2-mediated arachidonic acid metabolism in cancer-associated fibroblasts and myeloid-derived suppressor cells through multiple active components.
