淫羊藿苷
内分泌学
去卵巢大鼠
内科学
信号转导
淫羊藿
Mef2
HDAC4型
污渍
生物
化学
细胞生物学
雌激素
增强子
医学
转录因子
基因表达
生物化学
病理
替代医学
组蛋白甲基转移酶
中医药
基因
作者
Wenxia Zhao,Xiaoli Shan,Xueqin Li,Shuang Liu,L. Xia,Huihua Chen,Chen Zhang,Wei Guo,Ming Xu,Rong Lü,Pei Zhao
标识
DOI:10.1016/j.cbi.2023.110728
摘要
Icariin (ICA), a flavonoid phytoestrogen, was isolated from traditional Chinese medicine Yin Yang Huo (Epimedium brevicornu Maxim.). Previous studies reporting the cardioprotective effects of ICA are available; however, little is known about the impact of ICA on cardioprotection under conditions of reduced estrogen levels. This study aimed to provide detailed information regarding the antihypertrophic effects of ICA in ovariectomized female mice. Female mice were subjected to ovariectomy (OVX) and transverse aortic constriction and then orally treated with ICA at doses of 30, 60 or 120 mg/kg/day for 4 weeks. Morphological assessments, echocardiographic parameters, histological analyses, and immunofluorescence were performed to evaluate cardiac hypertrophy. Cardiomyocytes from mice or rats were stimulated using phenylephrine, and cell surface and hypertrophy markers were tested using immunofluorescence and qPCR. Western blotting, qPCR, and luciferase reporter gene assays were used to assess the expression of proteins and mRNA and further investigate the proteins related to the G-protein coupled estrogen receptor (GPER1) and CaMKII/HDAC4/MEF2C signaling pathways in vivo and in vitro. ICA blocks cardiac hypertrophy induced by pressure overload in OVX mice. Additionally, we demonstrated that ICA activated GPER1 and inhibited the nuclear export or promoted the nuclear import of histone deacetylase 4 (HDAC4) through regulation of phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and further improved the repression of myocyte enhancer factor-2C (MEF2C). ICA ameliorated cardiac hypertrophy in OVX mice by activating GPER1 and inhibiting the CaMKII/HDAC4/MEF2 signaling pathway.
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