School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China.
School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China.
Biomed Pharmacother. 2019 Dec;120:109487. doi: 10.1016/j.biopha.2019.109487. Epub 2019 Sep 29.
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 β-oxidation of fatty acids, including carnitine palmitoyltransterase-1α (CPT-1α), acyl-CoA dehydrogenase long chain (ACADL) and the major mitochondrial deacetylase enzyme sirtuin 3 (SIRT3). The upstream transcriptional regulator, peroxisome proliferator-activated receptor α (PPARα), 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 PPARα 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 PPARα is potential target in the management of HF.
心力衰竭（HF）导致全球发病率和死亡率增加。能量代谢紊乱和心肌细胞凋亡在 HF 的进展中起着至关重要的作用。人参皂苷 Rb3（G-Rb3）是一种源自人参的天然产物，具有心脏保护作用。G-Rb3 治疗 HF 的药理机制仍需阐明。在这项研究中，我们旨在通过体内和体外研究探讨 G-Rb3 对脂肪酸氧化和细胞凋亡的调节作用。通过氧葡萄糖剥夺/再灌注（OGD/R）刺激诱导心肌梗死（MI）诱导的 HF 小鼠模型和细胞 H9C2 损伤模型。结果表明，G-Rb3 可保护 MI 诱导的 HF 模型中的心脏功能。G-Rb3 治疗可上调参与脂肪酸β氧化的关键酶的表达，包括肉碱棕榈酰转移酶-1α（CPT-1α）、长链酰基辅酶 A 脱氢酶（ACADL）和主要线粒体去乙酰化酶 SIRT3。G-Rb3 治疗还上调了上游转录调节剂过氧化物酶体增殖物激活受体α（PPARα）。体外研究表明，G-Rb3 除了调节脂肪酸氧化外，还可以保护线粒体膜的完整性并发挥抗凋亡作用。令人印象深刻的是，在用 PPARα 抑制剂共同处理细胞后，G-Rb3 对能量代谢和细胞凋亡的调节作用被消除。我们的研究表明，G-Rb3 是一种有前途的药物，PPARα 是 HF 治疗的潜在靶点。
