Resveratrol is widely known for its antiaging properties and exerts cardiovascular protective effects in different experimental models. The role of resveratrol in regulating mitochondrial functions and dynamics during the cardiac aging process remains poorly understood. In this study, the effects of resveratrol on mitochondrial morphology and mitochondrial depolarization and on expressions of Drp1, parkin, PINK1, and LC3 were investigated in H9c2 cells after D-galactose treatment that induced senescent-like cardiomyocytes. The results show that downregulation of Drp1 markedly increased mitochondrial elongation. Senescent-like cardiomyocytes were more resistant to CCCP-induced mitochondrial depolarization, which was accompanied by suppressed expression of parkin, PINK1, and LC3-II. Resveratrol treatment significantly increased Drp1 expression, ameliorated mitochondrial elongation, and increased the mitochondrial translocations of parkin and PINK1. In addition, resveratrol significantly enhanced LC3-II expression and decreased TOM20-labeled mitochondrial content. Resveratrol also suppressed the phosphorylation of parkin and PINK1, which may relate to its abilities to degrade the impaired mitochondria in senescent-like cardiomyocytes. These findings show that suppressing mitochondrial elongation in a Drp1-dependent manner is involved in the effect of resveratrol on attenuating the development of aging cardiomyocytes. Activation of parkin and PINK1 may be a potential mechanism of resveratrol for treating cardiovascular complications related to aging.

Rg1 through modulation of GDH and MFN2 maintained mitochondrial dynamics that resulted in protection against H/R-induced cardiomyocyte injury. All these results put forward a new protective mechanism of Rg1 on the therapeutic potential in cardiac I/R disorders.

Background and Objective: Ischemic heart disease (IHD) has been the major issue of public health. Panax ginseng (ginseng) has been verified as an effective traditional Chinese medicines and exerted cardioprotective effect. This study aimed to investigate the polysaccharide fraction of ginseng on hypoxia/reoxygenation (H/R) injury in cardiomyocytes and the underlying mechanisms.Methods: Ginseng was extracted by ethanol and fractionated by high-speed counter current chromatography (HSCCC) and column separation. The cardioprotective effect was evaluated in H9c2 cardiomyocytes underwent H/R treatment. The cell viability, apoptosis and mitochondrial respiration were examined.Results: An acid polysaccharides fraction of ginseng (AP1) was identified the most effective fraction in protecting cardiomyocytes from H/R injury. AP1 restored the mitochondrial function by maintaining mitochondrial membrane potential (MMP), blocking the release of cytochrome C, and increasing the ATP generation and oxygen consumption rate (OCR) of cardiomyocytes. Meanwhile, AP1 induced the expression of glucocorticoid receptor (GR) and estrogen receptor (ER) which further activated reperfusion injury salvage kinase (RISK) pathway. Finally, AP1 increased nitric oxide (NO) production and regulated endothelial function by increasing endothelial NO synthase (eNOS) expression and decreasing inducible NOS (iNOS) expression in H/R injury.Conclusion: The results suggested that AP1 exerted a protective effect in myocardial H/R injury mainly through maintaining myocardial mitochondrial function, thereby inhibiting myocardial H/R caused apoptosis and increasing the expressions of GR and ER, which in turn mediated the activation of RISK pathway and eNOS-dependent mechanism to resist the reperfusion injury.

Background: The secreted glycoprotein Slit2, previously known as an axon guidance cue, has recently been found to protect tissues in pathological conditions; however, it is unknown whether Slit2 functions in cardiac ischemia-reperfusion (IR) injury. Methods: Langendorff-perfused isolated hearts from Slit2-overexpressing (Slit2-Tg) mice and C57BL/6J mice (background strain) were subjected to 20 min of global ischemia followed by 40 min of reperfusion. We compared Slit2-Tg with C57BL/6J mice in terms of left ventricular function and infarct size of post-IR hearts along with tissue histological and biochemical assessments (mRNA and protein expression, phosphorylation status, and myofilament contractile properties). Results: Slit2 played cardioprotective roles in maintaining contractile function and reducing infarct size in post-IR hearts. IR increased the expression of the Slit2 receptor Robo4 and the membrane receptor Slamf7, but these increases were suppressed by Slit2 overexpression post IR. This suppression was associated with inhibition of the nuclear translocation of NFκB p65 and reductions in IL-1β and IL-18 release into perfusates. Furthermore, Slit2 overexpression attenuated the increases in myofilamentassociated PKCs and phosphorylation of cTnI at Ser43 in the post-IR myocardium. The myofilament calcium sensitivity and actomyosin MgATPase activity were preserved in the post-IR Slit2 myocardium. Conclusion: Our work demonstrates that Slit2 inhibits inflammatory responses and maintains myofilament contractile properties, thus contributing, at least in part, to the prevention of structural and functional damage during IR.

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Erigeron multiradiatus (Lindl.) Benth. has been used in Tibet folk medicine to treat various inflammatory diseases. The aim of this study was to investigate antimyocardial ischemia and reperfusion (I/R) injury effect of caffeoylquinic acids derivatives of E. multiradiatus (AE) in vivo and to explain underling mechanism. AE was prepared using the whole plant of E. multiradiatus and contents of 6 caffeoylquinic acids determined through HPLC analysis. Myocardial I/R was induced by left anterior descending coronary artery occlusion for 30 minutes followed by 24 hours of reperfusion in rats. AE administration (10, 20, and 40 mg/kg) inhibited I/R-induced injury as indicated by decreasing myocardial infarct size, reducing of CK and LDH activities, and preventing ST-segment depression in dose-dependent manner. AE decreased cardiac tissue levels of proinflammatory factors TNF-α and IL-6 and attenuated leukocytes infiltration. AE was further demonstrated to significantly inhibit I-κB degradation, nuclear translocation of p-65 and phosphorylation of JNK. Our results suggested that cardioprotective effect of AE could be due to suppressing myocardial inflammatory response and blocking NF-κB and JNK activation pathway. Thus, caffeoylquinic acids might be the active compounds in E. multiradiatus on myocardial ischemia and be a potential natural drug for treating myocardial I/R injury.

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