Department of Integrative Bioscience and Biotechnology, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul 05006, Republic of Korea.
Department of Molecular Biology, Dankook University, Cheonan-si 31116, Republic of Korea.
Nutrients. 2023 Apr 6;15(7):1797. doi: 10.3390/nu15071797.
Shikonin, a natural ingredient produced by , has anti-inflammatory, anti-cancer, and anti-obesity effects. It also inhibits adipocyte differentiation; however, the underlying molecular and epigenetic mechanisms remain unclear. We performed RNA-sequencing of shikonin-treated 3T3-L1 cells. Gene ontology and gene set enrichment analysis showed that shikonin is significantly associated with genes related to adipogenesis, histone modification, and PPARγ. Shikonin treatment downregulated the mRNA expression of PPARγ-responsive genes and rosiglitazone-induced transcriptional activity of PPARγ. Microscale thermophoresis assays showed a K value 1.4 ± 0.13 μM for binding between shikonin and PPARγ. Glutathione S-transferase pull-down assays exhibited that shikonin blocked the rosiglitazone-dependent association of PPARγ with its coactivator CBP. In addition, shikonin decreased the enrichment of the active histone code H3K4me3 and increased the repressive code H3K27me3 of PPARγ target promoters. Shikonin is a PPARγ antagonist that suppresses adipogenesis by regulating the enrichment of histone codes during adipogenesis. Therefore, it may be used to treat obesity-related disorders via epigenetic changes.
紫草素是一种天然产物，具有抗炎、抗癌和抗肥胖作用。它还能抑制脂肪细胞分化；然而，其潜在的分子和表观遗传机制尚不清楚。我们对紫草素处理的 3T3-L1 细胞进行了 RNA-seq 分析。基因本体论和基因集富集分析表明，紫草素与与脂肪生成、组蛋白修饰和 PPARγ 相关的基因显著相关。紫草素处理下调了 PPARγ 反应基因的 mRNA 表达和罗格列酮诱导的 PPARγ 转录活性。微量热泳动分析显示紫草素与 PPARγ 的结合 K 值为 1.4±0.13 μM。谷胱甘肽 S-转移酶下拉实验表明，紫草素阻止了罗格列酮依赖的 PPARγ 与其共激活因子 CBP 的结合。此外，紫草素降低了 PPARγ 靶启动子上组蛋白 H3K4me3 的富集，并增加了组蛋白 H3K27me3 的抑制性编码。紫草素是一种 PPARγ 拮抗剂，通过调节脂肪生成过程中组蛋白编码的富集来抑制脂肪生成。因此，它可能通过表观遗传变化用于治疗肥胖相关疾病。
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