Department of Oriental Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Sinyong-Dong, Iksan, 570-749, South Korea.
Department of Agricultural Biology, National Institute of Agricultural Science, Rural Development Administration, Wanju, 55365, South Korea.
BMC Complement Altern Med. 2019 Jan 29;19(1):33. doi: 10.1186/s12906-018-2423-2.
Royal jelly (RJ) has been used traditionally for dietary, cosmetic and health purposes for a long time in different parts of the world. Scientific studies have also shown its numerous health-promoting properties including hypoglycemic and anti-hypercholesterolemic action. In this study, we investigated the anti-adipogenic activity of RJ in 3 T3-L1 cells and isolated the major responsible root component for the activity.
An active anti-adipogenic compound was isolated through bioassay-guided isolation process by successive treatment of RJ and its active fractions on 3 T3-L1 cell line. (E)-10-Hydroxy-2-decenoic Acid (10-HDA) was identified using NMR spectroscopy and ultra-performance liquid chromatography (UPLC). As 10-HDA showed significant anti-adipogenic activity with Oil Red O staining and TG content assay on 3 T3-L1 adipocytes, further study was carried out in molecular level for the expression of adipogenic transcription factors such as PPARγ, FABP4, C/EBPα, SREBP-1c, and Leptin. The effect of 10-HDA on preliminary molecules such as pAkt, pERK, C/EBPβ, and pCREB were studied in the early stage of adipogenesis. The effect of 10-HDA on reactive oxygen species (ROS) production in fully differentiating adipocytes was measured by nitro blue tetrazolium (NBT) assay.
Results showed that triacylglycerol accumulation and ROS production was markedly suppressed by 10-HDA. Preliminary molecules such as pAkt, pERK, pCERB, and C/EBPβ were found to be down-regulated by 10-HDA, which led to down-regulation of key adipogenic transcription factors such as PPARγ, FABP4, CEBPα, SREBP-1c, and Leptin on 3 T3-L1 adipocytes.
Our results suggest that anti-adipogenesis of 10-HDA on 3 T3-L1 adipocyte takes place via two mechanisms: inhibition of cAMP/PKA pathway and inhibition of p-Akt and MAPK dependent insulin signaling pathway. So it is considered that 10-HDA, a major component of RJ, can be a potential therapeutic medicine for obesity.
蜂王浆（RJ）在世界不同地区长期以来一直被传统用于饮食、美容和保健目的。科学研究还表明，它具有许多促进健康的特性，包括降血糖和抗高胆固醇作用。在这项研究中，我们研究了 RJ 在 3T3-L1 细胞中的抗脂肪生成活性，并分离出该活性的主要负责根成分。
通过生物测定指导的分离过程，连续处理 RJ 及其活性级分对 3T3-L1 细胞系，分离出活性抗脂肪生成化合物。（E）-10-羟基-2-癸烯酸（10-HDA）通过 NMR 光谱和超高效液相色谱（UPLC）进行鉴定。由于 10-HDA 在 3T3-L1 脂肪细胞中用油红 O 染色和 TG 含量测定显示出显著的抗脂肪生成活性，因此在分子水平上进一步研究了脂肪生成转录因子如 PPARγ、FABP4、C/EBPα、SREBP-1c 和 Leptin 的表达。在脂肪生成的早期阶段研究了 10-HDA 对初步分子如 pAkt、pERK、C/EBPβ 和 pCREB 的影响。通过硝基蓝四唑（NBT）测定测量 10-HDA 在完全分化的脂肪细胞中活性氧（ROS）产生的影响。
结果表明，10-HDA 明显抑制三酰甘油积累和 ROS 产生。发现初步分子如 pAkt、pERK、pCERB 和 C/EBPβ 被 10-HDA 下调，导致关键脂肪生成转录因子如 PPARγ、FABP4、CEBPα、SREBP-1c 和 Leptin 在 3T3-L1 脂肪细胞中的下调。
我们的结果表明，10-HDA 对 3T3-L1 脂肪细胞的抗脂肪生成作用通过两种机制发生：抑制 cAMP/PKA 途径和抑制 p-Akt 和 MAPK 依赖性胰岛素信号通路。因此，可以认为 10-HDA 是 RJ 的主要成分之一，可作为肥胖的潜在治疗药物。
