Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation
Ulcerative colitis (UC) is a common infl ammatory disease of the gastrointestinal tract. Traditional Chinese medicine (TCM) has long been used in Asia as a treatment for UC and Puerariae Radix (PR) is a reliable anti-diarrheal therapy. The aims of this study were to investigate the protective effect...
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| Format: | Article |
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Tsinghua University Press
2024-07-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | https://www.sciopen.com/article/10.26599/FSHW.2022.9250189 |
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| author | Yu Ga Yuanyuan Wei Qingyu Zhao Yimeng Fan Yannan Zhang Zhifang Zhang Sijia Hao Lixia Wang Zhifen Wang Jinlong Han Shuang Wu Zhihui Hao |
| author_facet | Yu Ga Yuanyuan Wei Qingyu Zhao Yimeng Fan Yannan Zhang Zhifang Zhang Sijia Hao Lixia Wang Zhifen Wang Jinlong Han Shuang Wu Zhihui Hao |
| author_sort | Yu Ga |
| collection | DOAJ |
| description | Ulcerative colitis (UC) is a common infl ammatory disease of the gastrointestinal tract. Traditional Chinese medicine (TCM) has long been used in Asia as a treatment for UC and Puerariae Radix (PR) is a reliable anti-diarrheal therapy. The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt (DSS)-induced UC model in mice and identify molecular mechanisms of PR action. The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identifi ed potential PR and UC targets using a network pharmacology (NP) approach were obtained to guide mouse experiments. A total of 180 peaks were identifi ed from PR including 48 flavonoids, 46 organic acids, 14 amino acids, 8 phenols, 8 carbohydrates, 7 alkaloids, 6 coumarins and 43 other constituents. NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC. A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice. PR also alleviated intestinal mucosal shedding, infl ammatory cell infi ltration and mucin loss. PR treatment suppressed upregulation of NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate-specific proteases-1 (caspase-1), apoptosis-associated speck-like (ASC) and gasdermin D (GSDMD) at both the protein and mRNA expression levels. The addition of a small molecule dual-specifi city phosphatase inhibitor NSC 95397 inhibited the positive effects of PR. These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 infl ammasome activation in mice. |
| format | Article |
| id | doaj-art-ab9711dec6374c75aa339e272640ab0d |
| institution | Kabale University |
| issn | 2097-0765 2213-4530 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-ab9711dec6374c75aa339e272640ab0d2025-01-10T06:56:48ZengTsinghua University PressFood Science and Human Wellness2097-07652213-45302024-07-011342266227610.26599/FSHW.2022.9250189Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activationYu Ga0Yuanyuan Wei1Qingyu Zhao2Yimeng Fan3Yannan Zhang4Zhifang Zhang5Sijia Hao6Lixia Wang7Zhifen Wang8Jinlong Han9Shuang Wu10Zhihui Hao11Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100086, ChinaInnovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100086, ChinaInnovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100086, ChinaInnovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100086, ChinaInnovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100086, ChinaInner Mongolia Medical University, Hohhot 010059, ChinaInner Mongolia Medical University, Hohhot 010059, ChinaChina Agricultural University Yantai Institute, Yantai 264670, ChinaShandong Academy of Agricultural Sciences, Jinan 250100, ChinaShandong Academy of Agricultural Sciences, Jinan 250100, ChinaShandong Academy of Agricultural Sciences, Jinan 250100, ChinaInnovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100086, ChinaUlcerative colitis (UC) is a common infl ammatory disease of the gastrointestinal tract. Traditional Chinese medicine (TCM) has long been used in Asia as a treatment for UC and Puerariae Radix (PR) is a reliable anti-diarrheal therapy. The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt (DSS)-induced UC model in mice and identify molecular mechanisms of PR action. The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identifi ed potential PR and UC targets using a network pharmacology (NP) approach were obtained to guide mouse experiments. A total of 180 peaks were identifi ed from PR including 48 flavonoids, 46 organic acids, 14 amino acids, 8 phenols, 8 carbohydrates, 7 alkaloids, 6 coumarins and 43 other constituents. NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC. A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice. PR also alleviated intestinal mucosal shedding, infl ammatory cell infi ltration and mucin loss. PR treatment suppressed upregulation of NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate-specific proteases-1 (caspase-1), apoptosis-associated speck-like (ASC) and gasdermin D (GSDMD) at both the protein and mRNA expression levels. The addition of a small molecule dual-specifi city phosphatase inhibitor NSC 95397 inhibited the positive effects of PR. These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 infl ammasome activation in mice.https://www.sciopen.com/article/10.26599/FSHW.2022.9250189puerariae radixulcerative colitismolecular mechanismspyroptosisnod-like receptor protein 3 inflammasome |
| spellingShingle | Yu Ga Yuanyuan Wei Qingyu Zhao Yimeng Fan Yannan Zhang Zhifang Zhang Sijia Hao Lixia Wang Zhifen Wang Jinlong Han Shuang Wu Zhihui Hao Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation Food Science and Human Wellness puerariae radix ulcerative colitis molecular mechanisms pyroptosis nod-like receptor protein 3 inflammasome |
| title | Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation |
| title_full | Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation |
| title_fullStr | Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation |
| title_full_unstemmed | Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation |
| title_short | Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation |
| title_sort | puerariae radix protects against ulcerative colitis in mice by inhibiting nlrp3 inflammasome activation |
| topic | puerariae radix ulcerative colitis molecular mechanisms pyroptosis nod-like receptor protein 3 inflammasome |
| url | https://www.sciopen.com/article/10.26599/FSHW.2022.9250189 |
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