Gegen Qinlian decoction (GQD) inhibits ulcerative colitis by modulating ferroptosis-dependent pathway in mice and organoids
Abstract Background Gegen Qinlian decoction (GQD) is a classic prescription for treating ulcerative colitis (UC) in traditional Chinese medicine. However, the therapeutic mechanism has not been fully clarified. Purpose In the present study, we aimed to evaluate the role of ferroptosis-mediated IEC d...
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BMC
2023-08-01
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| Series: | Chinese Medicine |
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| Online Access: | https://doi.org/10.1186/s13020-023-00819-4 |
| _version_ | 1797556451200204800 |
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| author | Xue Wang Jianye Quan Chengkui Xiu Jiali Wang Jiaqi Zhang |
| author_facet | Xue Wang Jianye Quan Chengkui Xiu Jiali Wang Jiaqi Zhang |
| author_sort | Xue Wang |
| collection | DOAJ |
| description | Abstract Background Gegen Qinlian decoction (GQD) is a classic prescription for treating ulcerative colitis (UC) in traditional Chinese medicine. However, the therapeutic mechanism has not been fully clarified. Purpose In the present study, we aimed to evaluate the role of ferroptosis-mediated IEC death in UC treated mice with GQD by using DSS-induced a colitis mouse model and RSL3-induced ferroptosis in intestinal organoids. Methods The effects of GQD on DSS-treated colitis were examined via daily body weight, DAI, colon length, HE staining, PAS staining, ZO-1 and Occludin immunohistochemical staining. Ferroptosis was determined by analysis of iron load, MDA, GSH, mitochondrial morphology, and expression of ferroptosis-associated proteins (GPX4, SLC7A11 and ACSL4). Results In vivo, GQD administration reduced body weight loss and DAI scores, increased colon length, and improved intestinal histological characteristics and epithelial barrier dysfunction. GQD administration obviously improved the levels of ferroptosis markers (iron load, MDA, GSH, and mitochondrial morphology) and the expression of ferroptosis-associated proteins (GPX4, SLC7A11 and ACSL4). Consistent with in vivo results, GQD administration partially reversed the levels of mtROS, Fe2+ and MDA in intestinal organoids induced by RSL3, and notably improved morphological destruction, histological damage and epithelial barrier dysfunction in organoids. Conclusions In this study, we demonstrated that ferroptosis was triggered in DSS-induced experimental colitis and that GQD adiministration could protect against colonic damage and intestinal epithelial barrier dysfunction by inhibiting ferroptosis. |
| first_indexed | 2024-03-10T17:03:05Z |
| format | Article |
| id | doaj.art-a128076d15b741fc9b68695471faf823 |
| institution | Directory Open Access Journal |
| issn | 1749-8546 |
| language | English |
| last_indexed | 2024-03-10T17:03:05Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj.art-a128076d15b741fc9b68695471faf8232023-11-20T10:55:08ZengBMCChinese Medicine1749-85462023-08-0118111310.1186/s13020-023-00819-4Gegen Qinlian decoction (GQD) inhibits ulcerative colitis by modulating ferroptosis-dependent pathway in mice and organoidsXue Wang0Jianye Quan1Chengkui Xiu2Jiali Wang3Jiaqi Zhang4Beijing Key Laboratory of Research of Chinese Medicine on Preventional and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical SciencesBeijing Key Laboratory of Research of Chinese Medicine on Preventional and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical SciencesBeijing Key Laboratory of Research of Chinese Medicine on Preventional and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical SciencesBeijing Key Laboratory of Research of Chinese Medicine on Preventional and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical SciencesXiyuan Hospital, China Academy of Chinese Medical SciencesAbstract Background Gegen Qinlian decoction (GQD) is a classic prescription for treating ulcerative colitis (UC) in traditional Chinese medicine. However, the therapeutic mechanism has not been fully clarified. Purpose In the present study, we aimed to evaluate the role of ferroptosis-mediated IEC death in UC treated mice with GQD by using DSS-induced a colitis mouse model and RSL3-induced ferroptosis in intestinal organoids. Methods The effects of GQD on DSS-treated colitis were examined via daily body weight, DAI, colon length, HE staining, PAS staining, ZO-1 and Occludin immunohistochemical staining. Ferroptosis was determined by analysis of iron load, MDA, GSH, mitochondrial morphology, and expression of ferroptosis-associated proteins (GPX4, SLC7A11 and ACSL4). Results In vivo, GQD administration reduced body weight loss and DAI scores, increased colon length, and improved intestinal histological characteristics and epithelial barrier dysfunction. GQD administration obviously improved the levels of ferroptosis markers (iron load, MDA, GSH, and mitochondrial morphology) and the expression of ferroptosis-associated proteins (GPX4, SLC7A11 and ACSL4). Consistent with in vivo results, GQD administration partially reversed the levels of mtROS, Fe2+ and MDA in intestinal organoids induced by RSL3, and notably improved morphological destruction, histological damage and epithelial barrier dysfunction in organoids. Conclusions In this study, we demonstrated that ferroptosis was triggered in DSS-induced experimental colitis and that GQD adiministration could protect against colonic damage and intestinal epithelial barrier dysfunction by inhibiting ferroptosis.https://doi.org/10.1186/s13020-023-00819-4Ulcerative colitisIEC deathFerroptosisIntestinal organoidsGegen Qinlian decoction |
| spellingShingle | Xue Wang Jianye Quan Chengkui Xiu Jiali Wang Jiaqi Zhang Gegen Qinlian decoction (GQD) inhibits ulcerative colitis by modulating ferroptosis-dependent pathway in mice and organoids Chinese Medicine Ulcerative colitis IEC death Ferroptosis Intestinal organoids Gegen Qinlian decoction |
| title | Gegen Qinlian decoction (GQD) inhibits ulcerative colitis by modulating ferroptosis-dependent pathway in mice and organoids |
| title_full | Gegen Qinlian decoction (GQD) inhibits ulcerative colitis by modulating ferroptosis-dependent pathway in mice and organoids |
| title_fullStr | Gegen Qinlian decoction (GQD) inhibits ulcerative colitis by modulating ferroptosis-dependent pathway in mice and organoids |
| title_full_unstemmed | Gegen Qinlian decoction (GQD) inhibits ulcerative colitis by modulating ferroptosis-dependent pathway in mice and organoids |
| title_short | Gegen Qinlian decoction (GQD) inhibits ulcerative colitis by modulating ferroptosis-dependent pathway in mice and organoids |
| title_sort | gegen qinlian decoction gqd inhibits ulcerative colitis by modulating ferroptosis dependent pathway in mice and organoids |
| topic | Ulcerative colitis IEC death Ferroptosis Intestinal organoids Gegen Qinlian decoction |
| url | https://doi.org/10.1186/s13020-023-00819-4 |
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