Ginsenoside Rb1 Enhances Atherosclerotic Plaque Stability by Improving Autophagy and Lipid Metabolism in Macrophage Foam Cells.
Ginsenoside Rb1 Enhances Atherosclerotic Plaque Stability by Improving Autophagy and Lipid Metabolism in Macrophage Foam Cells.
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人参皂苷 Rb1 通过改善巨噬细胞泡沫细胞的自噬和脂质代谢来增强动脉粥样硬化斑块的稳定性
DOI：
10.3389/fphar.2017.00727
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发表时间：
2017
影响因子：
5.6
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Qiao L;Zhang X;Liu M;Liu X;Dong M;Cheng J;Zhang X;Zhai C;Song Y;Lu H;Chen W
动脉粥样硬化（AS）是一种脂质驱动的疾病，其中巨噬细胞泡沫细胞通过增加血管脂质积聚和导致斑块不稳定而发挥关键作用。人参皂苷Rb 1（Ginsenoside Rb 1，Rb 1）是人参中含量最丰富的活性成分，具有促进脂质代谢、抑制脂质蓄积的作用。然而，其潜在机制仍不清楚。在这项研究中，Rb 1对脂质积累和斑块稳定性的影响，在体外和体内通过使用从C57 BL/6小鼠分离的原代腹腔巨噬细胞和AS模型在ApoE-/-小鼠。结果表明，Rb 1减少巨噬细胞泡沫细胞和动脉粥样硬化斑块中的脂质积聚。Rb 1治疗促进斑块的稳定性，通过修改斑块组成，通过激活自噬在体外和体内。透射电子显微镜进一步显示，在Rb 1处理的巨噬细胞泡沫细胞的自噬溶酶体的积累增加。然而，Rb 1对脂质积累的调节通过使用自噬相关基因5（Atg 5）小干扰RNA（siRNA）在体外进行自噬阻断而减弱。此外，Rb 1在体外和体内均显著增加AMPK磷酸化，AMPK抑制剂化合物C消除了Rb 1诱导的巨噬泡沫细胞自噬。总之，抗脂蛋白Rb 1通过诱导巨噬细胞自噬减少巨噬细胞泡沫细胞中的脂质积聚并增强动脉粥样硬化斑块的稳定性。我们的研究为Rb 1在预防和治疗AS中的可能应用提供了新的证据。
Atherosclerosis (AS) is a lipid-driven disease in which macrophage foam cells play a critical role by increasing vascular lipid accumulation and contributing to plaque instability. Ginsenoside Rb1 (Rb1), the most abundant active component of ginseng, has been found potently to promote lipid metabolism and attenuate lipid accumulation. However, the underlying mechanisms remain unclear. In this study, the effects of Rb1 on lipid accumulation and plaque stability were investigated both in vitro and in vivo by using primary peritoneal macrophages isolated from C57BL/6 mice and an AS model in ApoE-/- mice. The results showed that Rb1 reduced lipid accumulation both in macrophage foam cells and atherosclerotic plaques. Rb1 treatment promoted plaque stability by modifying plaque composition via the activation of autophagy both in vitro and in vivo. Transmission electron microscopy further showed an increased accumulation of autophagolysosomes in Rb1-treated macrophage foam cells. However, the modulation of lipid accumulation by Rb1 was attenuated by autophagy blockage using autophagy-related gene 5 (Atg5) small interfering RNA (siRNA) in vitro. In addition, Rb1 notably increased AMPK phosphorylation both in vitro and in vivo, and the AMPK inhibitor compound C abolished the Rb1-induced autophagy in macrophage foam cells. In conclusion, ginsenoside Rb1 reduced lipid accumulation in macrophage foam cells and enhanced atherosclerotic plaque stability by the induction of macrophage autophagy. Our study provides new evidence for the possible use of Rb1 in the prevention and treatment of AS.
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影响因子：
4.6
作者：
Cui YC;Pan CS;Yan L;Li L;Hu BH;Chang X;Liu YY;Fan JY;Sun K;-Li Q;Han JY
通讯作者：
Han JY
DOI：
10.1038/nri3520
发表时间：
2013-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1016/s1357-2725(97)00141-6
发表时间：
1998-03-01
影响因子：
4
作者：
Kim, YS;Kim, DS;Kim, SI
通讯作者：
Kim, SI
通过自噬调节脂质液滴。
影响因子：
10.9
作者：
Dong, Hanqing;Czaja, Mark J.
通讯作者：
Czaja, Mark J.
影响因子：
64.8
作者：
Singh, Rajat;Kaushik, Susmita;Wang, Yongjun;Xiang, Youqing;Novak, Inna;Komatsu, Masaaki;Tanaka, Keiji;Cuervo, Ana Maria;Czaja, Mark J.
通讯作者：
Czaja, Mark J.