Nakashima Ken-Ichi, Murakami Tohru, Tanabe Hiroki, Inoue Makoto
Laboratory of Natural Resources, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan.
Laboratory of Natural Resources, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan.
Biochim Biophys Acta. 2014 Oct;1840(10):3034-41. doi: 10.1016/j.bbagen.2014.06.011. Epub 2014 Jun 24.
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.
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.
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.
Drupanin, a component of BGP, is a novel RXR agonist with slight PPARγ agonistic activity.
This study revealed for the first time that BGP activates RXR and drupanin is an RXR agonist in its extract.
巴西绿蜂胶（BGP）是非洲化蜜蜂（意大利蜜蜂）从艾草中采集的一种树脂物质，用作民间药物。我们目前的研究探索了BGP的视黄酸X受体（RXR）激动活性，并在其提取物中鉴定出一种RXR激动剂。
使用荧光素酶报告基因检测评估RXRα激动活性。通过连续硅胶柱和反相柱色谱从BGP乙醇提取物中分离RXRα激动剂。通过受体-配体对接模拟预测分离出的RXRα激动剂与RXRα蛋白之间的相互作用。使用核受体（NR）辅因子检测来评估分离出的RXRα激动剂是否与包括RXR和过氧化物酶体增殖物激活受体（PPAR）在内的各种NR结合。我们进一步研究了其对3T3-L1成纤维细胞脂肪生成的影响。
我们鉴定出二氢杨梅素为RXRα激动剂，EC50值为4.8±1.0μM。二氢杨梅素以相似的程度激活三种RXR亚型，并适度激活PPARγ。此外，二氢杨梅素诱导3T3-L1成纤维细胞脂肪生成并提高aP2 mRNA水平。
二氢杨梅素是BGP的一种成分，是一种新型RXR激动剂，具有轻微的PPARγ激动活性。
本研究首次揭示BGP激活RXR，且二氢杨梅素是其提取物中的一种RXR激动剂。
