Liuwei Dihuang prevents postmenopausal atherosclerosis and endothelial cell apoptosis via inhibiting DNMT1-medicated ERα methylation. (24th April 2020)

• Record Type: Journal Article
• Authors: Chen, Qi; Zhang, Yuhan; Meng, Qinghai; Wang, Suyun; Yu, Xichao; Cai, Danfeng; Cheng, Peng; Li, Yu; Bian, Huimin
• Is Part Of: Journal of ethnopharmacology. Volume 252(2020)
• Publication Date: 2020-04-24
• Subjects: Liuwei Dihuang -- Atherosclerosis -- Estrogen receptor α -- DNA methylation -- ApoE−/- mice -- HUVECs; LWDH Liuwei Dihuang -- HUVECs human umbilical vein endothelial cells -- ERα estrogen receptor α -- DNMTs DNA methyltransferases -- RT-PCR real-time polymerase chain reaction -- BSP bisulfite sequencing PCR -- HPLC-MS High-performance liquid chromatography-tandem mass spectrometry -- SAM S-Adenosyl methionine -- SAH S-Adenosyl homocysteine -- AS atherosclerosis -- CVD cardiovascular disease -- Hcy homocysteine -- HRT hormone replacement therapy -- VSMCs vascular smooth muscle cells -- Ovx ovariectomized -- eNOS endothelial nitric oxide synthase -- NO nitric oxide; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2019.112531
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: The classical and traditional Chinese medicine prescription, Liuwei Dihuang (LWDH), has been commonly used to treat the menopausal syndrome. It has been reported that LWDH could improve estrogen receptor α (ERα) expression to prevent atherosclerosis (AS), while the mechanism of LWDH on regulating ERα expression was still unknown. Aim of the study: To reveal the mechanism of LWDH on regulating the ERα expression. Materials and methods: The protective effect of LWDH on Hcy-induced apoptosis of human umbilical vein endothelial cells (HUVECs) was examined. The expression of ERα and DNA methyltransferases 1 (DNMT1) were detected by Western blot and real-time polymerase chain reaction (RT-PCR). The methylation rate of the ERα gene was assayed by the bisulfite sequencing PCR (BSP). High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) was applied to determine the level of S-Adenosyl methionine (SAM) and S-Adenosyl homocysteine (SAH). In vivo, the ApoE −/- mice were ovariectomized to establish postmenopausal atherosclerosis (AS) model. Results: In vitro study showed that LWDH protects HUVECs from Hcy-induced apoptosis. Treatment with LWDH significantly increased the ERα expression and reduced the methylation rate of the ERα gene by inhibiting the DNMT1 expression. The level of main methyl donor SAM and the ration of SAM/SAH were reduced by LWDH. In vivo, LWDH prevented the formation of plaque and reduced the concentration of Hcy. In addition, LWDH upregulated the ERα expression, as well as inhibiting the expression of DNMT1 in atherosclerotic mice. Conclusions: LWDH exerted protective effects on postmenopausal AS mice, and HUVECs treated with Hcy. LWDH increased of ERα expression via inhibiting DNMT1-dependent ERα methylation. Graphical abstract: Image 1