Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
Nutrients. 2022 Sep 21;14(19):3920. doi: 10.3390/nu14193920.
Fibroblast growth factor 21 (FGF21), which is mainly synthesized and secreted by the liver, plays a crucial role in systemic glucose and lipid metabolism, ameliorating metabolic diseases. In this study, we screened the WAKANYAKU library derived from medicinal herbs to identify compounds that can activate expression in mouse hepatocyte AML12 cells. We identified root extract and one of its components, wogonin, as an activator of expression. Wogonin also enhanced the expression of activating transcription factor 4 (ATF4) by a mechanism other than ER stress. Knockdown of ATF4 by siRNA suppressed wogonin-induced expression, highlighting its essential role in wogonin's mode of action. Thus, our results indicate that wogonin would be a strong candidate for a therapeutic to improve metabolic diseases by enhancing hepatic FGF21 production.
成纤维细胞生长因子 21（FGF21）主要由肝脏合成和分泌，在全身葡萄糖和脂质代谢中发挥关键作用，可改善代谢性疾病。在本研究中，我们筛选了源自草药的 WAKANYAKU 文库，以鉴定能够激活 AML12 细胞中表达的化合物。我们发现根提取物及其成分之一黄苓素可激活表达。黄苓素还通过不同于 ER 应激的机制增强激活转录因子 4（ATF4）的表达。siRNA 敲低 ATF4 可抑制黄苓素诱导的表达，突出了其在黄苓素作用模式中的重要作用。因此，我们的研究结果表明，黄苓素可能是一种通过增强肝脏 FGF21 产生来改善代谢性疾病的有前途的治疗药物。
