Yi Sang Ah, Lee Jieun, Park Sun Kyu, Kim Jeom Yong, Park Jong Woo, Lee Min Gyu, Nam Ki Hong, Park Jee Hun, Oh Hwamok, Kim Saetbyul, Han Jihoon, Kim Bo Kyung, Jo Dong-Gyu, Han Jeung-Whan
School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
Research Institute, Green Cross WellBeing, Seongnam, Republic of Korea.
J Ginseng Res. 2020 Jan;44(1):58-66. doi: 10.1016/j.jgr.2018.08.002. Epub 2018 Aug 8.
The biological and pharmacological effects of BST204, a fermented ginseng extract, have been reported in various disease conditions. However, its molecular action in metabolic disease remains poorly understood. In this study, we identified the antiadipogenic activity of BST204 resulting from its inhibition of the S6 kinase 1 (S6K1) signaling pathway.
The inhibitory effects of BST204 on S6K1 signaling were investigated by immunoblot, nuclear fractionation, immunoprecipitation analyses. The antiadipogenic effect of BST204 was evaluated by measuring mRNA levels of adipogenic genes and by chromatin immunoprecipitation and quantitative real-time polymerase chain reaction analysis.
Treatment with BST204 inhibited activation and nuclear translocation of S6K1, further decreasing the interaction between S6K1 and histone H2B in 10T1/2 mesenchymal stem cells. Subsequently, phosphorylation of H2B at serine 36 (H2BS36p) by S6K1 was reduced by BST204, inducing an increase in the mRNA expression of , , and , which disturbed adipogenic differentiation and promoted myogenic and early osteogenic gene expression. Consistently, BST204 treatment during adipogenic commitment suppressed the expression of adipogenic marker genes and lipid drop formation.
Our results indicate that BST204 blocks adipogenesis of mesenchymal stem cells through the inhibition of S6K1-mediated histone phosphorylation. This study suggests the potential therapeutic strategy using BST204 to combat obesity and musculoskeletal diseases.
发酵人参提取物BST204的生物学和药理作用已在多种疾病状态下得到报道。然而，其在代谢性疾病中的分子作用仍知之甚少。在本研究中，我们确定了BST204通过抑制S6激酶1（S6K1）信号通路而具有的抗脂肪生成活性。
通过免疫印迹、细胞核分级分离、免疫沉淀分析研究BST204对S6K1信号的抑制作用。通过测量脂肪生成基因的mRNA水平以及染色质免疫沉淀和定量实时聚合酶链反应分析来评估BST204的抗脂肪生成作用。
用BST204处理可抑制S6K1的激活和核转位，进一步减少10T1/2间充质干细胞中S6K1与组蛋白H2B之间的相互作用。随后，BST204降低了S6K1介导的丝氨酸36处H2B的磷酸化（H2BS36p），导致 、 和 的mRNA表达增加，这扰乱了脂肪生成分化并促进了肌源性和早期成骨基因表达。一致地，在脂肪生成过程中用BST204处理可抑制脂肪生成标记基因的表达和脂滴形成。
我们的结果表明，BST204通过抑制S6K1介导的组蛋白磷酸化来阻断间充质干细胞的脂肪生成。本研究提示了使用BST204对抗肥胖和肌肉骨骼疾病的潜在治疗策略。
