Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect

Abstract Ouabagenin (OBG) is an aglycone of the cardiotonic steroid ouabain and until now was considered a biologically inactive biosynthetic precursor. Herein, we revealed that OBG functions as a novel class of ligand for the liver X receptor (LXR). Luciferase reporter assays and in silico docking...

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Autores principales:	Satoru Tamura, Maiko Okada, Shigeaki Kato, Yasuharu Shinoda, Norifumi Shioda, Kohji Fukunaga, Kumiko Ui-Tei, Minoru Ueda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b859fcce77d6432195f802e39f6294b0
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spelling	oai:doaj.org-article:b859fcce77d6432195f802e39f6294b02021-12-02T15:08:48ZOuabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect10.1038/s41598-018-20663-z2045-2322https://doaj.org/article/b859fcce77d6432195f802e39f6294b02018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20663-zhttps://doaj.org/toc/2045-2322Abstract Ouabagenin (OBG) is an aglycone of the cardiotonic steroid ouabain and until now was considered a biologically inactive biosynthetic precursor. Herein, we revealed that OBG functions as a novel class of ligand for the liver X receptor (LXR). Luciferase reporter assays and in silico docking studies suggested that OBG has LXR-selective agonistic activity. In addition, OBG repressed the expression of epithelial sodium channel (ENaC), a LXR target gene, without causing hepatic steatosis, a typical side effect of conventional LXR ligands. This remarkable biological activity can be attributed to a unique mode of action; the LXR agonist activity mainly proceeds through the LXRβ subtype without affecting LXRα, unlike conventional LXR ligands. Thus, OBG is a novel class of LXR ligand that does not cause severe side effects, with potential for use as an antihypertensive diuretic or a tool compound for exploring LXR subtype-specific biological functions.Satoru TamuraMaiko OkadaShigeaki KatoYasuharu ShinodaNorifumi ShiodaKohji FukunagaKumiko Ui-TeiMinoru UedaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Satoru Tamura Maiko Okada Shigeaki Kato Yasuharu Shinoda Norifumi Shioda Kohji Fukunaga Kumiko Ui-Tei Minoru Ueda Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect
description	Abstract Ouabagenin (OBG) is an aglycone of the cardiotonic steroid ouabain and until now was considered a biologically inactive biosynthetic precursor. Herein, we revealed that OBG functions as a novel class of ligand for the liver X receptor (LXR). Luciferase reporter assays and in silico docking studies suggested that OBG has LXR-selective agonistic activity. In addition, OBG repressed the expression of epithelial sodium channel (ENaC), a LXR target gene, without causing hepatic steatosis, a typical side effect of conventional LXR ligands. This remarkable biological activity can be attributed to a unique mode of action; the LXR agonist activity mainly proceeds through the LXRβ subtype without affecting LXRα, unlike conventional LXR ligands. Thus, OBG is a novel class of LXR ligand that does not cause severe side effects, with potential for use as an antihypertensive diuretic or a tool compound for exploring LXR subtype-specific biological functions.
format	article
author	Satoru Tamura Maiko Okada Shigeaki Kato Yasuharu Shinoda Norifumi Shioda Kohji Fukunaga Kumiko Ui-Tei Minoru Ueda
author_facet	Satoru Tamura Maiko Okada Shigeaki Kato Yasuharu Shinoda Norifumi Shioda Kohji Fukunaga Kumiko Ui-Tei Minoru Ueda
author_sort	Satoru Tamura
title	Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect
title_short	Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect
title_full	Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect
title_fullStr	Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect
title_full_unstemmed	Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect
title_sort	ouabagenin is a naturally occurring lxr ligand without causing hepatic steatosis as a side effect
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/b859fcce77d6432195f802e39f6294b0
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Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect

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