Sigesbeckia pubescens makino alleviates ulcerative colitis in mice by modulating the Nrf2/Keap1 pathway
BackgroundUlcerative colitis (UC) is a prevalent immune-mediated inflammatory bowel disease characterized by mucus secretion, hematochezia, and diarrhea. This study compared the therapeutic effects of three Siegesbeckiae Herba (SH) species used in traditional Chinese medicine—Sigesbeckia orientalis...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1588525/full |
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| author | Qiu-Shuo Ma Qi-Ling Chen Guo-Ping Wu Ya-Wen Yao Yu-Xin Fan Ke-Gang Linghu Jun-Ming Chen Wei Xiong Hua Yu Hua Yu |
| author_facet | Qiu-Shuo Ma Qi-Ling Chen Guo-Ping Wu Ya-Wen Yao Yu-Xin Fan Ke-Gang Linghu Jun-Ming Chen Wei Xiong Hua Yu Hua Yu |
| author_sort | Qiu-Shuo Ma |
| collection | DOAJ |
| description | BackgroundUlcerative colitis (UC) is a prevalent immune-mediated inflammatory bowel disease characterized by mucus secretion, hematochezia, and diarrhea. This study compared the therapeutic effects of three Siegesbeckiae Herba (SH) species used in traditional Chinese medicine—Sigesbeckia orientalis L (SO), Sigesbeckia pubescens Makino (SP), and Sigesbeckia glabrescens Makino (SG) — in dextran sulfate sodium (DSS)-induced UC mice.MethodsUC was induced in C57BL/6 mice with 3% DSS for 7 days. Cytokine levels in serum and colon tissues were measured by enzyme-linked immunosorbent assay. Protein and gene expression were analyzed using Western blotting and PCR. Histopathological changes were assessed via hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence. Fecal specimens were collected for gut microbiota analysis. An in vitro UC model was also established in NCM460 cells using lipopolysaccharide (LPS), and Caco-2 cells were used to examine intestinal mucosal integrity.ResultsSP substantially decreased the disease activity index, enhanced colon shortening, and mitigated histological damage in comparison to the model group. Mechanistic investigations demonstrated that SP functioned via the activation of the Nrf2/Keap1 pathway, markedly increased the activity of the antioxidant enzyme glutathione in colon tissues, decreased the concentration of the oxidative marker malondialdehyde, and upregulated the expression of the downstream genes H O -1 and NQO1.ConclusionThe study reveals for the first time the differences in efficacy of different species of SH and its molecular mechanism, demonstrating that SP increases oxidative defense via the activation of the Nrf2/Keap1 pathway, therefore mitigating colitis and oxidative damage in UC mice. This discovery not only establishes a scientific foundation for the selective preference of SH species but also offers a novel technique for the creation of natural pharmaceuticals aimed at the Nrf2 pathway for the treatment of UC. |
| format | Article |
| id | doaj-art-c4cd090040df4b6c8d604ff7295719a1 |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-c4cd090040df4b6c8d604ff7295719a12025-08-20T02:19:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15885251588525Sigesbeckia pubescens makino alleviates ulcerative colitis in mice by modulating the Nrf2/Keap1 pathwayQiu-Shuo Ma0Qi-Ling Chen1Guo-Ping Wu2Ya-Wen Yao3Yu-Xin Fan4Ke-Gang Linghu5Jun-Ming Chen6Wei Xiong7Hua Yu8Hua Yu9State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, ChinaThe High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang City, Guizhou, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, ChinaSchool of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, ChinaMacao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, ChinaBackgroundUlcerative colitis (UC) is a prevalent immune-mediated inflammatory bowel disease characterized by mucus secretion, hematochezia, and diarrhea. This study compared the therapeutic effects of three Siegesbeckiae Herba (SH) species used in traditional Chinese medicine—Sigesbeckia orientalis L (SO), Sigesbeckia pubescens Makino (SP), and Sigesbeckia glabrescens Makino (SG) — in dextran sulfate sodium (DSS)-induced UC mice.MethodsUC was induced in C57BL/6 mice with 3% DSS for 7 days. Cytokine levels in serum and colon tissues were measured by enzyme-linked immunosorbent assay. Protein and gene expression were analyzed using Western blotting and PCR. Histopathological changes were assessed via hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence. Fecal specimens were collected for gut microbiota analysis. An in vitro UC model was also established in NCM460 cells using lipopolysaccharide (LPS), and Caco-2 cells were used to examine intestinal mucosal integrity.ResultsSP substantially decreased the disease activity index, enhanced colon shortening, and mitigated histological damage in comparison to the model group. Mechanistic investigations demonstrated that SP functioned via the activation of the Nrf2/Keap1 pathway, markedly increased the activity of the antioxidant enzyme glutathione in colon tissues, decreased the concentration of the oxidative marker malondialdehyde, and upregulated the expression of the downstream genes H O -1 and NQO1.ConclusionThe study reveals for the first time the differences in efficacy of different species of SH and its molecular mechanism, demonstrating that SP increases oxidative defense via the activation of the Nrf2/Keap1 pathway, therefore mitigating colitis and oxidative damage in UC mice. This discovery not only establishes a scientific foundation for the selective preference of SH species but also offers a novel technique for the creation of natural pharmaceuticals aimed at the Nrf2 pathway for the treatment of UC.https://www.frontiersin.org/articles/10.3389/fphar.2025.1588525/fullulcerative colitissiegesbeckiae herbaSigesbeckia pubescens makinoantioxidantNrf2 |
| spellingShingle | Qiu-Shuo Ma Qi-Ling Chen Guo-Ping Wu Ya-Wen Yao Yu-Xin Fan Ke-Gang Linghu Jun-Ming Chen Wei Xiong Hua Yu Hua Yu Sigesbeckia pubescens makino alleviates ulcerative colitis in mice by modulating the Nrf2/Keap1 pathway Frontiers in Pharmacology ulcerative colitis siegesbeckiae herba Sigesbeckia pubescens makino antioxidant Nrf2 |
| title | Sigesbeckia pubescens makino alleviates ulcerative colitis in mice by modulating the Nrf2/Keap1 pathway |
| title_full | Sigesbeckia pubescens makino alleviates ulcerative colitis in mice by modulating the Nrf2/Keap1 pathway |
| title_fullStr | Sigesbeckia pubescens makino alleviates ulcerative colitis in mice by modulating the Nrf2/Keap1 pathway |
| title_full_unstemmed | Sigesbeckia pubescens makino alleviates ulcerative colitis in mice by modulating the Nrf2/Keap1 pathway |
| title_short | Sigesbeckia pubescens makino alleviates ulcerative colitis in mice by modulating the Nrf2/Keap1 pathway |
| title_sort | sigesbeckia pubescens makino alleviates ulcerative colitis in mice by modulating the nrf2 keap1 pathway |
| topic | ulcerative colitis siegesbeckiae herba Sigesbeckia pubescens makino antioxidant Nrf2 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1588525/full |
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