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黄芪甲苷IV通过抑制p38丝裂原活化蛋白激酶信号通路,抑制血小板衍生生长因子-BB刺激的血管平滑肌细胞增殖和迁移。

Astragaloside IV inhibits platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells via the inhibition of p38 MAPK signaling.

作者信息

Chen Zhuo, Cai Ying, Zhang Wenliang, Liu Xinzhou, Liu Suixin

机构信息

Cardiac Rehabilitation Center, Department of Rehabilitation, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.

出版信息

Exp Ther Med. 2014 Oct;8(4):1253-1258. doi: 10.3892/etm.2014.1905. Epub 2014 Aug 14.

Abstract

Astragaloside IV (AS-IV), the major active component extracted from , has been demonstrated to exhibit protective effects on the cardiovascular, immune, digestive and nervous systems; thus, has been widely used in traditional Chinese medicine. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is closely associated with the initiation and progression of cardiovascular diseases, including atherosclerosis and restenosis. However, the effects of AS-IV on VSMCs remain unknown. For the first time, the present study demonstrated that AS-IV markedly suppressed platelet-derived growth factor (PDGF)-BB-stimulated cellular proliferation and migration of HDMEC-a human dermal VSMCs (HDVSMCs). Further investigation into the underlying molecular mechanisms demonstrated that the administration of AS-IV attenuated the PDGF-BB-stimulated switch of HDVSMCs into a proliferative phenotype. Furthermore, AS-IV inhibited the PDGF-BB-induced expression of cell cycle-associated proteins, as well as the upregulation of matrix metalloproteinase (MMP)2, but not MMP9. In addition, AS-IV was shown to downregulate the activation of p38 mitogen-activated protein kinase (MAPK) signaling induced by PDGF-BB in HDVSMCs. Therefore, the observations of the present study indicate that AS-IV inhibits PDGF-BB-stimulated VSMC proliferation and migration, possibly by inhibiting the activation of the p38 MAPK signaling pathway. Thus, AS-IV may be useful for the treatment of vascular diseases.

摘要

黄芪甲苷IV(AS-IV)是从黄芪中提取的主要活性成分,已被证明对心血管、免疫、消化和神经系统具有保护作用,因此在传统中药中被广泛应用。血管平滑肌细胞(VSMCs)的异常增殖和迁移与心血管疾病(包括动脉粥样硬化和再狭窄)的发生和发展密切相关。然而,AS-IV对VSMCs的作用尚不清楚。本研究首次表明,AS-IV显著抑制血小板衍生生长因子(PDGF)-BB刺激的人真皮血管平滑肌细胞(HDVSMCs)的细胞增殖和迁移。对潜在分子机制的进一步研究表明,AS-IV给药减弱了PDGF-BB刺激的HDVSMCs向增殖表型的转变。此外,AS-IV抑制了PDGF-BB诱导的细胞周期相关蛋白的表达,以及基质金属蛋白酶(MMP)2的上调,但不影响MMP9。此外,AS-IV被证明可下调PDGF-BB诱导的HDVSMCs中p38丝裂原活化蛋白激酶(MAPK)信号通路的激活。因此,本研究的观察结果表明,AS-IV可能通过抑制p38 MAPK信号通路的激活来抑制PDGF-BB刺激的VSMC增殖和迁移。因此,AS-IV可能有助于治疗血管疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd35/4151649/fb90dcaf5087/ETM-08-04-1253-g00.jpg

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