Novel FXR agonist nelumal A suppresses colitis and inflammation-related colorectal carcinogenesis

Abstract FXR is a member of the nuclear receptor superfamily and bile acids are endogenous ligands of FXR. FXR activation has recently been reported to inhibit intestinal inflammation and tumour development. This study aimed to investigate whether the novel FXR agonist nelumal A, the active compound...

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Autores principales:	Tsuneyuki Miyazaki, Yohei Shirakami, Taku Mizutani, Akinori Maruta, Takayasu Ideta, Masaya Kubota, Hiroyasu Sakai, Takashi Ibuka, Salvatore Genovese, Serena Fiorito, Vito Alessandro Taddeo, Francesco Epifano, Takuji Tanaka, Masahito Shimizu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7ce700ce2ce149d58144ddadc34ce01f
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spelling	oai:doaj.org-article:7ce700ce2ce149d58144ddadc34ce01f2021-12-02T14:12:08ZNovel FXR agonist nelumal A suppresses colitis and inflammation-related colorectal carcinogenesis10.1038/s41598-020-79916-52045-2322https://doaj.org/article/7ce700ce2ce149d58144ddadc34ce01f2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79916-5https://doaj.org/toc/2045-2322Abstract FXR is a member of the nuclear receptor superfamily and bile acids are endogenous ligands of FXR. FXR activation has recently been reported to inhibit intestinal inflammation and tumour development. This study aimed to investigate whether the novel FXR agonist nelumal A, the active compound of the plant Ligularia nelumbifolia, can prevent colitis and colorectal carcinogenesis. In a mouse colitis model, dextran sodium sulfate-induced colonic mucosal ulcer and the inflammation grade in the colon significantly reduced in mice fed diets containing nelumal A. In an azoxymethane/dextran sodium sulfate-induced mouse inflammation-related colorectal carcinogenesis model, the mice showed decreased incidence of colonic mucosal ulcers and adenocarcinomas in nelumal A-treated group. Administration of nelumal A also induced tight junctions, antioxidant enzymes, and FXR target gene expression in the intestine, while it decreased the gene expression of bile acid synthesis in the liver. These findings suggest that nelumal A effectively attenuates colonic inflammation and suppresses colitis-related carcinogenesis, presumably through reduction of bile acid synthesis and oxidative damage. This agent may be potentially useful for treatment of inflammatory bowel diseases as well as their related colorectal cancer chemoprevention.Tsuneyuki MiyazakiYohei ShirakamiTaku MizutaniAkinori MarutaTakayasu IdetaMasaya KubotaHiroyasu SakaiTakashi IbukaSalvatore GenoveseSerena FioritoVito Alessandro TaddeoFrancesco EpifanoTakuji TanakaMasahito ShimizuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tsuneyuki Miyazaki Yohei Shirakami Taku Mizutani Akinori Maruta Takayasu Ideta Masaya Kubota Hiroyasu Sakai Takashi Ibuka Salvatore Genovese Serena Fiorito Vito Alessandro Taddeo Francesco Epifano Takuji Tanaka Masahito Shimizu Novel FXR agonist nelumal A suppresses colitis and inflammation-related colorectal carcinogenesis
description	Abstract FXR is a member of the nuclear receptor superfamily and bile acids are endogenous ligands of FXR. FXR activation has recently been reported to inhibit intestinal inflammation and tumour development. This study aimed to investigate whether the novel FXR agonist nelumal A, the active compound of the plant Ligularia nelumbifolia, can prevent colitis and colorectal carcinogenesis. In a mouse colitis model, dextran sodium sulfate-induced colonic mucosal ulcer and the inflammation grade in the colon significantly reduced in mice fed diets containing nelumal A. In an azoxymethane/dextran sodium sulfate-induced mouse inflammation-related colorectal carcinogenesis model, the mice showed decreased incidence of colonic mucosal ulcers and adenocarcinomas in nelumal A-treated group. Administration of nelumal A also induced tight junctions, antioxidant enzymes, and FXR target gene expression in the intestine, while it decreased the gene expression of bile acid synthesis in the liver. These findings suggest that nelumal A effectively attenuates colonic inflammation and suppresses colitis-related carcinogenesis, presumably through reduction of bile acid synthesis and oxidative damage. This agent may be potentially useful for treatment of inflammatory bowel diseases as well as their related colorectal cancer chemoprevention.
format	article
author	Tsuneyuki Miyazaki Yohei Shirakami Taku Mizutani Akinori Maruta Takayasu Ideta Masaya Kubota Hiroyasu Sakai Takashi Ibuka Salvatore Genovese Serena Fiorito Vito Alessandro Taddeo Francesco Epifano Takuji Tanaka Masahito Shimizu
author_facet	Tsuneyuki Miyazaki Yohei Shirakami Taku Mizutani Akinori Maruta Takayasu Ideta Masaya Kubota Hiroyasu Sakai Takashi Ibuka Salvatore Genovese Serena Fiorito Vito Alessandro Taddeo Francesco Epifano Takuji Tanaka Masahito Shimizu
author_sort	Tsuneyuki Miyazaki
title	Novel FXR agonist nelumal A suppresses colitis and inflammation-related colorectal carcinogenesis
title_short	Novel FXR agonist nelumal A suppresses colitis and inflammation-related colorectal carcinogenesis
title_full	Novel FXR agonist nelumal A suppresses colitis and inflammation-related colorectal carcinogenesis
title_fullStr	Novel FXR agonist nelumal A suppresses colitis and inflammation-related colorectal carcinogenesis
title_full_unstemmed	Novel FXR agonist nelumal A suppresses colitis and inflammation-related colorectal carcinogenesis
title_sort	novel fxr agonist nelumal a suppresses colitis and inflammation-related colorectal carcinogenesis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7ce700ce2ce149d58144ddadc34ce01f
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Novel FXR agonist nelumal A suppresses colitis and inflammation-related colorectal carcinogenesis

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