Ginsenoside Rb3 regulates energy metabolism and apoptosis in cardiomyocytes via activating PPARα pathway
Ginsenoside Rb3 regulates energy metabolism and apoptosis in cardiomyocytes via activating PPARα pathway
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人参皂苷 Rb3 通过激活 PPAR α 通路调节心肌细胞能量代谢和凋亡
DOI：
10.1016/j.biopha.2019.109487
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发表时间：
2019-12-01
影响因子：
7.5
通讯作者：
Wang, Yong
中科院分区：
文献类型：
--
作者：
Chen, Xu;Wang, Qiyan;Wang, Yong
心力衰竭（HF）导致全球发病率和死亡率增加。心肌细胞的能量代谢紊乱和凋亡在心力衰竭的发生发展中起着重要作用。人参皂苷Rb 3（Ginsenoside Rb 3，G-Rb 3）是人参中的一种天然产物，具有保护心脏的作用。G-Rb 3治疗HF的药理学机制仍有待阐明。本研究旨在通过体内和体外研究探讨G-Rb 3对脂肪酸氧化和细胞凋亡的调控作用。采用心肌梗死（MI）诱导的HF小鼠模型和氧糖剥夺/再灌注（OGD/R）刺激诱导的H9 C2细胞损伤模型。结果表明，G-Rb 3对心肌缺血性心力衰竭模型的心功能有保护作用。G-Rb 3处理上调了参与脂肪酸β-氧化的关键酶的表达，包括肉毒碱棕榈酰转移酶-1 α（CPT-1 α）、酰基辅酶A脱氢酶长链（ACADL）和主要的线粒体脱乙酰酶sirtuin 3（SIRT 3）。上游转录调节因子，过氧化物酶体增殖物激活受体α（PPAR α），也上调G-Rb 3治疗。体外研究表明，G-Rb 3除了调节脂肪酸氧化外，还具有保护线粒体膜完整性和抗凋亡作用。令人印象深刻的是，在与PPAR α抑制剂共同处理细胞后，G-Rb 3对能量代谢和凋亡的调节作用被废除。我们的研究表明，G-Rb 3是一种有前途的药物，PPARa是治疗HF的潜在靶点。
Heart failure (HF) leads to an increase in morbidity and mortality globally. Disorders of energy metabolism and apoptosis of cardiomyocytes are critically involved in the progression of HF. Ginsenoside Rb3 (G-Rb3) is a natural product derived from ginseng that has cardio-protective effect. The pharmacological mechanism of G-Rb3 in the treatment of HF remains to be clarified. In this study, we aimed to explore the regulative effects of G-Rb3 on fatty acids oxidation and apoptosis by in vivo and in vitro studies. Myocardial infarction (MI)-induced HF mice model and a cellular H9C2 injury model was induced by oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The results showed that G-Rb3 could protect heart functions in MI-induced HF model. G-Rb3 treatment up-regulated expressions of key enzymes involved in beta-oxidation of fatty acids, including carnitine palmitoyltransterase-1 alpha (CPT-1 alpha), acyl-CoA dehydrogenase long chain (ACADL) and the major mitochondrial deacetylase enzyme sirtuin 3 (SIRT3). The upstream transcriptional regulator, peroxisome proliferator-activated receptor alpha (PPAR alpha), was also up-regulated by G-Rb3 treatment. In vitro study demonstrated that G-Rb3 could protect mitochondrial membrane integrity and exert anti-apoptotic effects, in addition to regulating fatty acids oxidation. Impressively, after cells were co-treated with PPAR alpha inhibitor, the regulative effects of G-Rb3 on energy metabolism and apoptosis were abrogated. Our study suggests that G-Rb3 is a promising agent and PPARa is potential target in the management of HF.