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

Satoru Tamura, Maiko Okada, Shigeaki Kato, Yasuharu Shinoda, Norifumi Shioda, Kohji Fukunaga, Kumiko Ui-Tei, Minoru Ueda

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Article number2305
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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