Identification of a naturally occurring retinoid X receptor agonist from Brazilian green propolis

Background: Brazilian green propolis (BGP), a resinous substance produced from Baccharis dracunculifolia by Africanized honey bees (Apis mellifera), is used as a folk medicine. Our present study explores the retinoid X receptor (RXR) agonistic activity of BGP and the identification of an RXR agonist in its extract.

Methods: RXRα agonistic activity was evaluated using a luciferase reporter gene assay. Isolation of the RXRα Agonist from the ethanolic extract of BGP was performed using successive silica gel and a reversed phase column chromatography. The interaction between the isolated RXRα Agonist and RXRα protein was predicted by a receptor-ligand docking simulation. The nuclear receptor (NR) cofactor assay was used to estimate whether the isolated RXRα Agonist bound to various NRs, including RXRs and peroxisome proliferator-activated receptors (PPARs). We further examined its effect on adipogenesis in 3T3-L1 fibroblasts.

Results: We identified drupanin as an RXRα Agonist with an EC50 value of 4.8 ± 1.0 μM. Drupanin activated three RXR subtypes by a similar amount and activated PPARγ moderately. Additionally, drupanin induced adipogenesis and elevated aP2 mRNA levels in 3T3-L1 fibroblasts.

Conclusions: Drupanin, a component of BGP, is a novel RXR agonist with slight PPARγ agonistic activity.

General significance: This study revealed for the first time that BGP activates RXR and drupanin is an RXR agonist in its extract.

Bioactive natural compound; Drupanin; Peroxisome proliferator-activated receptor; Propolis; Retinoid X receptor.