The retinoid X receptor (RXR) plays
a critical role in transcriptional
regulation via formation of an RXR homodimer or heterodimers with
partner nuclear receptors. Despite the numerous beneficial effects,
only a limited number of naturally occurring RXR agonists are known.
In this report, two prenylated flavanones (1 and 2) isolated from Sophora tonkinensis were
identified as new rexinoids that preferentially activated RXRs, relative
to the retinoic acid receptor. The activities of 1 and 2 were the most potent among naturally occurring rexinoids,
yet 2 orders of magnitude lower than the synthetic rexinoid bexarotene.
Compounds 1 and 2 activated particular RXR
heterodimers in a manner similar to bexarotene. A microarray assay
followed by quantitative real-time polymerase chain reaction analyses
on RNAs isolated from C2C12 myotubes treated with 1 or 2 demonstrated that they significantly increased mRNA levels
of lipoprotein lipase, angiopoietin-like protein 4, and heme oxygenase-1.
In contrast, bexarotene preferentially potentiated transcription of
genes involved in lipogenesis and lipid metabolism such as sterol
regulatory element-binding protein-1, fatty acid synthase, and apolipoprotein
D by a liver X receptor agonist. In this study, we have demonstrated
that two newly identified naturally occurring rexinoids, 1 and 2, possess properties different from bexarotene.