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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 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 LXR? subtype without affecting LXR?, 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.

SUBMITTER: Tamura S 

PROVIDER: S-EPMC5797171 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Tamura Satoru S   Okada Maiko M   Kato Shigeaki S   Shinoda Yasuharu Y   Shioda Norifumi N   Fukunaga Kohji K   Ui-Tei Kumiko K   Ueda Minoru M  

Scientific reports 20180202 1


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 s  ...[more]

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