Cardioprotective effect of ethanol extracts of Sugemule-3 decoction on isoproterenol-induced heart failure in Wistar rats through regulation of mitochondrial dynamics.

Cardioprotective effect of ethanol extracts of Sugemule-3 decoction on isoproterenol-induced heart failure in Wistar rats through regulation of mitochondrial dynamics.
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Sugemule-3 煎剂乙醇提取物通过调节线粒体动力学对异丙肾上腺素诱导的 Wistar 大鼠心力衰竭的心脏保护作用。

DOI:
10.1016/j.jep.2021.114669
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发表时间:
2021-09
影响因子:
5.4
通讯作者:
Yu LiJun
Yu LiJun
中科院分区:
医学2区
文献类型:
--
作者:
Zhen Dong;Na RiSong;Wang Yu;Bai Xue;Fu DanNi;Wei ChengXi;Liu MingJie;Yu LiJun

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舒格木勒-3汤(Sugemule-3汤剂,SD-3)是蒙医常用方剂,主要由白豆蔻(Amomumumulatum Sol.)ex Maton)、白菊生(Lactucasativa L.)和Biba(Piper longumL.)。SD-3对心血管疾病有显著疗效,本研究旨在探讨SD-3乙醇提取物对异丙肾上腺素(ISO)诱导的大鼠心力衰竭(HF)的保护作用及其可能机制。雄性Wistar大鼠100只,随机分为5组:对照组、ISO(HF)组和SD-3不同剂量组(0.4,0.2,0.1g/kg/d)。腹腔注射异丙肾上腺素建立心衰大鼠模型。超声心动图评价左室功能。HE染色和Masson染色观察心肌损伤和纤维化情况。Western-blot分析各组细胞凋亡蛋白表达及线粒体动力学变化。此外,心肌细胞线粒体的结构变化,也观察了通过透射电镜。Results 15化合物检测到SD-3的乙醇提取物,包括胡椒碱,胡椒碱等。大鼠与ISO管理显示出显着的左心室功能下降。ISO组心肌组织病理学改变为局部坏死、间质水肿、心肌纤维化。SD-3处理显著抑制ISO的这些作用。结果发现,ISO可增加Bax、cleaved-PARP和cleaved-caspase-3、-7-9蛋白的表达,破坏线粒体融合与分裂的平衡,改变线粒体形态。SD-3的乙醇提取物可以重新平衡线粒体的融合和分裂,并改善由ISO诱导的线粒体形态异常。结论本研究表明,SD-3的乙醇提取物改善异丙肾上腺素诱导的心肌肥厚和纤维化,通过抑制心肌细胞凋亡和调节线粒体动力学。
Ethnopharmacological relevanceSugemule-3 decoction (SD-3) is a commonly used prescription in Mongolian medicine which composed of the herbs Baidoukou (the fruit ofAmomumcompactumSol. ex Maton), Baijusheng (the fruit ofLactucasativaL.) and Biba (Piper longumL.). SD-3 has remarkable effect on the cardiovascular diseases, but its pharmacological mechanism has not been elucidated.Aim of this studyTo evaluate the cardioprotective effects and the potential mechanisms of the ethanol extracts of SD-3 against isoproterenol (ISO)-induced heart failure (HF) in rats.Material and methodsThe ethanol extracts of SD-3 were prepared and analyzed by LC-ESI-MS/MS. One hundred male Wistar rats were randomly divided into five groups: control, ISO (HF) and different doses of SD-3 (0.4, 0.2, 0.1 g/kg/d) groups. HF model rats were established by intraperitoneal injecting of ISO. The left ventricular function was evaluated by echocardiography. Myocardial injury and fibrosis were examined by hematoxylin-eosin (HE) and Masson staining. Western-blot analysis was performed to determine the protein expression of apoptosis and mitochondrial dynamics in all the groups. Moreover, the structural changes in the mitochondria of cardiomyocytes were also observed by transmission electron microscopy.ResultsFifteen compounds were detected in the ethanol extracts of SD-3, include piperine, piperanine, etc. Rats administered with ISO showed a significant decline in the left ventricular function. The cardiac histopathological changes such as local necrosis, interstitial edema, and cardiac fibrosis were also observed in the ISO group. The treatment with SD-3 significantly inhibited these effects of ISO. ISO was found to increase the protein expression of Bax, cleaved-PARP and cleaved-caspase-3, -7 -9, destroy the balance between mitochondrial fusion and fission, and alter the mitochondrial morphology. The ethanol extracts of SD-3 could rebalance mitochondrial fusion and fission, and ameliorates the morphological abnormalities induced by ISO in mitochondria.ConclusionThe current study demonstrated that ethanol extracts of SD-3 improved isoprenaline-induced cardiac hypertrophy and fibrosis through inhibiting cardiomyocyte apoptosis and regulating the mitochondrial dynamics.
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