Alisol A 24-Acetate, a Triterpenoid Derived from Alisma orientale, Inhibits Ox-LDL-Induced Phenotypic Transformation and Migration of Rat Vascular Smooth Muscle Cells through Suppressing ERK1/2 Signaling.
Alisol A 24-Acetate, a Triterpenoid Derived from Alisma orientale, Inhibits Ox-LDL-Induced Phenotypic Transformation and Migration of Rat Vascular Smooth Muscle Cells through Suppressing ERK1/2 Signaling.
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Alisol A 24-Acetate 是一种从泽泻中提取的三萜类化合物，通过抑制 ERK1/2 信号传导来抑制 Ox-LDL 诱导的大鼠血管平滑肌细胞表型转化和迁移。
DOI：
10.1159/000448715
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Chen Li-Dian
中科院分区：
文献类型：
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作者：
Xue Xie-Hua;Zhou Xiao-Mao;Wei Wei;Chen Tong;Su Qing-Ping;Tao Jing;Chen Li-Dian
Alisol A 24-acetate 是从泽泻中提取的一种三萜类化合物，具有抗动脉粥样硬化作用。本研究的目的是评估24-乙酸泽泻醇A对氧化低密度脂蛋白（Ox-LDL）诱导的大鼠血管平滑肌细胞（VSMC）表型转化和迁移的抑制作用，并探讨其潜在机制。 VSMCs 用泽泻醇 A 24-乙酸酯和特异性细胞外信号调节激酶 (ERK) 抑制剂 U0126 预处理，然后在体外用 50 mg/l Ox-LDL 刺激。使用免疫细胞化学测定VSMC表型标记物SM22α的表达，并使用划痕伤口愈合实验检测VSMC的迁移。测定基质金属蛋白酶（MMP）-9、MMP-2、磷酸化ERK1/2（pERK1/2）和总ERK的表达。 Ox-LDL处理导致SM22α表达减少，VSMC向合成表型转化，MMP-2和MMP-9合成增加，VSMC迁移距离延长和pERK1/2表达上调，而添加泽泻醇A 24-乙酸酯或U0126导致SM22α表达升高，VSMC向收缩表型转化， MMP-2和MMP-9表达减少，细胞迁移距离缩短，pERK1/2表达减少。本研究结果表明，泽泻醇A 24-acetate有效逆转表型转化并抑制VSMCs迁移，这可能与抑制ERK1/2信号通路有关。
Alisol A 24-acetate, a triterpenoid extracted from Alisma orientale, has shown antiatherosclerotic actions. The purpose of this study was to evaluate the inhibition of alisol A 24-acetate on oxidized low-density lipoprotein (Ox-LDL)-induced phenotypic transformation and migration of rat vascular smooth muscle cells (VSMCs), and to explore the underlying mechanisms. VSMCs were pretreated with alisol A 24-acetate and a specific extracellular signal-regulated kinase (ERK) inhibitor, U0126, and then stimulated with 50 mg/l Ox-LDL in vitro. The expression of VSMC phenotypic marker SM22α was determined using immunocytochemistry, and the migration of VSMCs was detected using a scratch-wound healing assay. The expression of matrix metalloproteinase (MMP)-9, MMP-2, phosphorylated ERK1/2 (pERK1/2) and total ERK was determined. Ox-LDL treatment caused a reduction in SM22α expression, VSMC transformation to the synthetic phenotype, increased MMP-2 and MMP-9 synthesis, the extension of VSMC migration distance and the upregulation of pERK1/2 expression, while the addition of alisol A 24-acetate or U0126 resulted in the elevation of SM22α expression, VSMC transformation to the contractile phenotype, a reduction in MMP-2 and MMP-9 expression, the shortening of cell migration distance and decreased pERK1/2 expression. The results of this study demonstrate that alisol A 24-acetate effectively reverses the phenotypic transformation and inhibits the migration of VSMCs, which may be associated with the suppression of the ERK1/2 signaling pathway.