Quinazolinone Derivative MR2938 Protects DSS-Induced Barrier Dysfunction in Mice Through Regulating Gut Microbiota
<b>Background/Objectives</b>: Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), is characterized by colorectal immune infiltration and significant microbiota compositional changes. Gut microbiota homeostasis is necessary to maintain the healthy state of humans. MR2938,...
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2025-01-01
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| author | Ling Lv Mireguli Maimaitiming Jichen Yang Shuli Xia Xin Li Pingyuan Wang Zhiqing Liu Chang-Yun Wang |
| author_facet | Ling Lv Mireguli Maimaitiming Jichen Yang Shuli Xia Xin Li Pingyuan Wang Zhiqing Liu Chang-Yun Wang |
| author_sort | Ling Lv |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), is characterized by colorectal immune infiltration and significant microbiota compositional changes. Gut microbiota homeostasis is necessary to maintain the healthy state of humans. MR2938, a quinazolin-4(3H)-one derivative derived from the marine natural product penipanoid C, alleviated DSS-induced colitis in a dose-dependent manner. Herein, we aimed to investigate the impact of MR2938 on the gut microbiota in dextran sodium sulfate (DSS)-induced colitis in mice and to elucidate the role of the gut microbiota in the therapeutic mechanism of MR2938 for alleviating colitis. <b>Methods</b>: Acute colitis was induced with DSS in mice. Mice were administered with 100 mg/kg or 50 mg/kg of MR2938. Cecal content was also preserved in liquid nitrogen and subsequently analyzed following 16S RNA sequencing. Antibiotic cocktail-induced microbiome depletion was performed to further investigate the relationship between MR2938 and gut microbiota. The inflammatory factor levels were performed by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Alcian blue staining and immunofluorescence were used to estimate the intestinal barrier. <b>Results</b>: The 16S rRNA sequencing revealed microbiota modulation by MR2938. Compared with the model group, the 100 mg/kg MR2938 group was associated with higher abundances of <i>Entercoccus</i> and a lower abundance of <i>Staphylococcus</i>, while the 50 mg/kg MR2938 group was associated with higher abundances of <i>Lactobacillus</i> and a lower abundance of <i>Staphylococcus</i>. The antibiotic-mediated microbiota depletion experiments demonstrated that the gut microbiota primarily contributed to barrier function protection, with little impact on inflammatory factor levels during the MR2938 treatment. <b>Conclusions</b>: These findings suggest that intestinal flora play a crucial role in MR2938’s therapeutic mechanism for alleviating colitis. |
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| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-7556796dbed0481abb4142675ab1b5da2025-01-24T13:45:28ZengMDPI AGPharmaceuticals1424-82472025-01-0118112310.3390/ph18010123Quinazolinone Derivative MR2938 Protects DSS-Induced Barrier Dysfunction in Mice Through Regulating Gut MicrobiotaLing Lv0Mireguli Maimaitiming1Jichen Yang2Shuli Xia3Xin Li4Pingyuan Wang5Zhiqing Liu6Chang-Yun Wang7MOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, ChinaMOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, ChinaMOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, ChinaMOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, ChinaMOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, ChinaMOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, ChinaMOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, ChinaMOE Key Laboratory of Marine Drugs, MOE Key Laboratory of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Institute of Evolution & Marine Biodiversity, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China<b>Background/Objectives</b>: Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), is characterized by colorectal immune infiltration and significant microbiota compositional changes. Gut microbiota homeostasis is necessary to maintain the healthy state of humans. MR2938, a quinazolin-4(3H)-one derivative derived from the marine natural product penipanoid C, alleviated DSS-induced colitis in a dose-dependent manner. Herein, we aimed to investigate the impact of MR2938 on the gut microbiota in dextran sodium sulfate (DSS)-induced colitis in mice and to elucidate the role of the gut microbiota in the therapeutic mechanism of MR2938 for alleviating colitis. <b>Methods</b>: Acute colitis was induced with DSS in mice. Mice were administered with 100 mg/kg or 50 mg/kg of MR2938. Cecal content was also preserved in liquid nitrogen and subsequently analyzed following 16S RNA sequencing. Antibiotic cocktail-induced microbiome depletion was performed to further investigate the relationship between MR2938 and gut microbiota. The inflammatory factor levels were performed by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Alcian blue staining and immunofluorescence were used to estimate the intestinal barrier. <b>Results</b>: The 16S rRNA sequencing revealed microbiota modulation by MR2938. Compared with the model group, the 100 mg/kg MR2938 group was associated with higher abundances of <i>Entercoccus</i> and a lower abundance of <i>Staphylococcus</i>, while the 50 mg/kg MR2938 group was associated with higher abundances of <i>Lactobacillus</i> and a lower abundance of <i>Staphylococcus</i>. The antibiotic-mediated microbiota depletion experiments demonstrated that the gut microbiota primarily contributed to barrier function protection, with little impact on inflammatory factor levels during the MR2938 treatment. <b>Conclusions</b>: These findings suggest that intestinal flora play a crucial role in MR2938’s therapeutic mechanism for alleviating colitis.https://www.mdpi.com/1424-8247/18/1/123colitisintestinal barrier functiongastrointestinal microbiomequinazolinones |
| spellingShingle | Ling Lv Mireguli Maimaitiming Jichen Yang Shuli Xia Xin Li Pingyuan Wang Zhiqing Liu Chang-Yun Wang Quinazolinone Derivative MR2938 Protects DSS-Induced Barrier Dysfunction in Mice Through Regulating Gut Microbiota Pharmaceuticals colitis intestinal barrier function gastrointestinal microbiome quinazolinones |
| title | Quinazolinone Derivative MR2938 Protects DSS-Induced Barrier Dysfunction in Mice Through Regulating Gut Microbiota |
| title_full | Quinazolinone Derivative MR2938 Protects DSS-Induced Barrier Dysfunction in Mice Through Regulating Gut Microbiota |
| title_fullStr | Quinazolinone Derivative MR2938 Protects DSS-Induced Barrier Dysfunction in Mice Through Regulating Gut Microbiota |
| title_full_unstemmed | Quinazolinone Derivative MR2938 Protects DSS-Induced Barrier Dysfunction in Mice Through Regulating Gut Microbiota |
| title_short | Quinazolinone Derivative MR2938 Protects DSS-Induced Barrier Dysfunction in Mice Through Regulating Gut Microbiota |
| title_sort | quinazolinone derivative mr2938 protects dss induced barrier dysfunction in mice through regulating gut microbiota |
| topic | colitis intestinal barrier function gastrointestinal microbiome quinazolinones |
| url | https://www.mdpi.com/1424-8247/18/1/123 |
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