Integrative Biology Journals

Natural Products and Bioprospecting ›› 2026, Vol. 16 ›› Issue (5): 76-76.DOI: 10.1007/s13659-026-00636-w

• ORIGINAL ARTICLE • Previous Articles     Next Articles

Huanglian-Wendan Decoction alleviates DSS-induced colitis by modulating the gut microbiota and protecting against intestinal injury via suppression of colonic apoptosis and endoplasmic reticulum stress

Liang Li1, Xinyi Zhan1, Hidayat Ullah2,3,4, Wenxian Guo1, Ping Gui5, Weijie Peng1, Quanxi Mei1, Weibo Dai1, Yuting Duan6, Xia Yuan7, Xianjing Hu2,3,4,5   

  1. 1. Pharmacology Laboratory, Zhongshan Hospital, Guangzhou University of Chinese Medicine, Zhongshan, 528401, Guangdong, 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. Dongguan Key Laboratory of Fundamental Research and Clinical Application of Toxic Chinese Medicine, The First Dongguan Affiliated Hospital, School of Pharmacy, Guangdong Medical University, Dongguan, 523121, PR China;
    4. School of Pharmacy, Dongguan Branch, National Engineering Research Center for Modernization of Traditional Chinese Medicine, Guangdong Medical University, Dongguan, 523808, PR China;
    5. Department of Proctology, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523121, PR China;
    6. Evidence-Based Medicine Center, The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou, 510140, PR China;
    7. Cancer Center, The First Huizhou Affiliated Hospital of Guangdong Medical University, Huizhou, 516000, PR China
  • Received:2026-01-04 Accepted:2026-04-22 Online:2026-10-08
  • Supported by:
    This study was financially supported by the Special Project for Medical-Health of Science and Technology Plan of Zhongshan, Guangdong, China (2019B1016 and 2021SYF10), Natural Science Foundation of Guangdong Province (2023A1515011116), Special Project for Clinical and Basic Sci&Tech Innovation of Guangdong Medical University (4SG25302G, GDMULCJC2025132), Discipline Construction Project of Guangdong Medical University (4SG24002G, 4SG25325G), Dongguan Science and Technology of Social Development Program (20231800939832, 20231800935732), Key Research and Development Project of Huizhou, China (2023CZ010001), Guangdong Province Basic and Applied Basic Research Fund (Guangdong-Huizhou Joint Fund, 2023B1515120023), Student Innovation Research and Entrepreneurship Training of Guangdong Medical University (GDMU2023132, GDMU2023264), and State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases Fund (SKL-HIDCA-2025-GD1, SKL-HIDCA-2025-GD5) and National Foreign Experts Individual Project (4RS25004).

Huanglian-Wendan Decoction alleviates DSS-induced colitis by modulating the gut microbiota and protecting against intestinal injury via suppression of colonic apoptosis and endoplasmic reticulum stress

Liang Li1, Xinyi Zhan1, Hidayat Ullah2,3,4, Wenxian Guo1, Ping Gui5, Weijie Peng1, Quanxi Mei1, Weibo Dai1, Yuting Duan6, Xia Yuan7, Xianjing Hu2,3,4,5   

  1. 1. Pharmacology Laboratory, Zhongshan Hospital, Guangzhou University of Chinese Medicine, Zhongshan, 528401, Guangdong, 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. Dongguan Key Laboratory of Fundamental Research and Clinical Application of Toxic Chinese Medicine, The First Dongguan Affiliated Hospital, School of Pharmacy, Guangdong Medical University, Dongguan, 523121, PR China;
    4. School of Pharmacy, Dongguan Branch, National Engineering Research Center for Modernization of Traditional Chinese Medicine, Guangdong Medical University, Dongguan, 523808, PR China;
    5. Department of Proctology, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523121, PR China;
    6. Evidence-Based Medicine Center, The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou, 510140, PR China;
    7. Cancer Center, The First Huizhou Affiliated Hospital of Guangdong Medical University, Huizhou, 516000, PR China
  • 通讯作者: Weibo Dai,E-mail:daiweibo007@163.com;Yuting Duan,E-mail:duanyt@gzhmu.edu.cn;Xianjing Hu,E-mail:huxj2003@163.com
  • 基金资助:
    This study was financially supported by the Special Project for Medical-Health of Science and Technology Plan of Zhongshan, Guangdong, China (2019B1016 and 2021SYF10), Natural Science Foundation of Guangdong Province (2023A1515011116), Special Project for Clinical and Basic Sci&Tech Innovation of Guangdong Medical University (4SG25302G, GDMULCJC2025132), Discipline Construction Project of Guangdong Medical University (4SG24002G, 4SG25325G), Dongguan Science and Technology of Social Development Program (20231800939832, 20231800935732), Key Research and Development Project of Huizhou, China (2023CZ010001), Guangdong Province Basic and Applied Basic Research Fund (Guangdong-Huizhou Joint Fund, 2023B1515120023), Student Innovation Research and Entrepreneurship Training of Guangdong Medical University (GDMU2023132, GDMU2023264), and State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases Fund (SKL-HIDCA-2025-GD1, SKL-HIDCA-2025-GD5) and National Foreign Experts Individual Project (4RS25004).

Abstract: Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent intestinal inflammation and gut microbiota dysbiosis. Huanglian-Wendan Decoction (HLWDD) has been clinically used for IBD treatment; however, its underlying mechanisms remain unclear. In this study, a dextran sulfate sodium (DSS, 2.25%)-induced IBD mouse model was established to evaluate the therapeutic effects of HLWDD. The protective mechanisms were investigated in colon tissues of DSS-induced mice using ELISA, immunoblotting, histological, and immunohistochemical analyses. In addition, the impact of HLWDD on gut microbiota dysbiosis was analyzed using 16S rRNA sequencing. Antibiotic treatment was applied before DSS administration to deplete gut microbiota and verify the role of microbial modulation. Furthermore, the phytochemical constituents of HLWDD were characterized using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The results demonstrated that HLWDD markedly alleviated DSS-induced colitis, as evidenced by reduced body weight loss, rectal bleeding, colon shortening, and disease activity index (DAI) scores. Mechanistically, HLWDD suppressed inflammatory responses in colon tissues by inhibiting the TLR4/MyD88/NF-κB and IL-6/JAK2/STAT3 signaling pathways, while enhancing epithelial barrier integrity through upregulation of ZO-1, Occludin, Claudin-1, and Mucin-2. In addition, HLWDD attenuated endoplasmic reticulum stress (ERS) and apoptosis by downregulating CHOP, phospho-eIF2α, cleaved caspase-3, and Bax, while increasing Bcl-2 expression in colonic tissues. Microbiota analysis revealed an increased abundance of beneficial bacterial genera such as Akkermansia and Escherichia-Shigella-related commensals, along with enrichment of beneficial bacterial families including Ruminococcaceae, Lachnospiraceae, and Verrucomicrobiaceae, whereas potentially harmful taxa such as Escherichia and Paraprevotella were reduced. HLWDD also increased the production of short-chain fatty acids (SCFAs), including acetate, butyrate, and isobutyrate, thereby promoting intestinal homeostasis. Importantly, the protective effects of HLWDD were largely abolished following antibiotic-mediated gut microbiota depletion, confirming the essential role of microbial modulation in its therapeutic action. Collectively, these findings suggest that HLWDD ameliorates IBD by regulating gut microbiota composition and function, thereby inhibiting colonic ER stress and apoptosis and restoring intestinal barrier integrity. This study provides mechanistic evidence supporting the potential clinical application of HLWDD as a novel therapeutic strategy for IBD.

Key words: Inflammatory bowel disease, Chinese medicine formula, Huanglian-Wendan Decoction, Apoptosis, Endoplasmic stress, Gut microbiota

摘要: Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent intestinal inflammation and gut microbiota dysbiosis. Huanglian-Wendan Decoction (HLWDD) has been clinically used for IBD treatment; however, its underlying mechanisms remain unclear. In this study, a dextran sulfate sodium (DSS, 2.25%)-induced IBD mouse model was established to evaluate the therapeutic effects of HLWDD. The protective mechanisms were investigated in colon tissues of DSS-induced mice using ELISA, immunoblotting, histological, and immunohistochemical analyses. In addition, the impact of HLWDD on gut microbiota dysbiosis was analyzed using 16S rRNA sequencing. Antibiotic treatment was applied before DSS administration to deplete gut microbiota and verify the role of microbial modulation. Furthermore, the phytochemical constituents of HLWDD were characterized using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The results demonstrated that HLWDD markedly alleviated DSS-induced colitis, as evidenced by reduced body weight loss, rectal bleeding, colon shortening, and disease activity index (DAI) scores. Mechanistically, HLWDD suppressed inflammatory responses in colon tissues by inhibiting the TLR4/MyD88/NF-κB and IL-6/JAK2/STAT3 signaling pathways, while enhancing epithelial barrier integrity through upregulation of ZO-1, Occludin, Claudin-1, and Mucin-2. In addition, HLWDD attenuated endoplasmic reticulum stress (ERS) and apoptosis by downregulating CHOP, phospho-eIF2α, cleaved caspase-3, and Bax, while increasing Bcl-2 expression in colonic tissues. Microbiota analysis revealed an increased abundance of beneficial bacterial genera such as Akkermansia and Escherichia-Shigella-related commensals, along with enrichment of beneficial bacterial families including Ruminococcaceae, Lachnospiraceae, and Verrucomicrobiaceae, whereas potentially harmful taxa such as Escherichia and Paraprevotella were reduced. HLWDD also increased the production of short-chain fatty acids (SCFAs), including acetate, butyrate, and isobutyrate, thereby promoting intestinal homeostasis. Importantly, the protective effects of HLWDD were largely abolished following antibiotic-mediated gut microbiota depletion, confirming the essential role of microbial modulation in its therapeutic action. Collectively, these findings suggest that HLWDD ameliorates IBD by regulating gut microbiota composition and function, thereby inhibiting colonic ER stress and apoptosis and restoring intestinal barrier integrity. This study provides mechanistic evidence supporting the potential clinical application of HLWDD as a novel therapeutic strategy for IBD.

关键词: Inflammatory bowel disease, Chinese medicine formula, Huanglian-Wendan Decoction, Apoptosis, Endoplasmic stress, Gut microbiota