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Aims Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease and lacks for safe and effective drug to therapy completely. Ginsenoside-Rg1 is one of the main components of ginseng and has been proved to counteract a variety of diseases. However, there is currently a lack of sufficient evidence to support the efficacy of ginsenoside-Rg1 in the treatment of NAFLD. Our aim was to investigate whether Ginsenoside-Rg1 is a potential drug for NAFLD. Main methods NAFLD model in rats was established by giving a high-fat diet (HFD), ginsenoside-Rg1 was intragastrically administered 100 mg/kg/d for 8 weeks in NAFLD rat. Serum biochemical indices were measured. Liver tissues were stained with hematoxylin and eosin (HE) and oil red O. Total RNA was extracted from liver and was used for high throughput sequencing to identify the changes of transcriptome. The relevant hub genes were verified by quantitative real-time PCR and western blot. Key findings Serum biochemical analysis indicated that ginsenoside-Rg1 improved liver function. Additionally, the staining of HE and oil red O indicated ginsenoside-Rg1 could remit pathology process of NAFLD. The transcriptome changes also support this result and reveals Atf3 and Acox2 were key genes. Significance Taken together, these results suggest that the efficiency of ginsenoside-Rg1 against NAFLD and confirmed that ginsenoside-Rg1 is a potential effective drug in treatment of NAFLD.

Oxidative/nitrative stress plays an important role in myocardial ischemia/reperfusion (MI/R) injury. Notch1 participates in the regulation of cardiogenesis and cardiac response to hypertrophic stress, but the function of Notch1 signaling in MI/R has not been explored. This study aims to determine the role of Notch1 in MI/R, and investigate whether Notch1 confers cardioprotection. Notch1 specific small interfering RNA (siRNA, 20 μg) or Jagged1 (a Notch ligand, 12 μg) was delivered through intramyocardial injection. 48 h after injection, mice were subjected to 30 min of myocardial ischemia followed by 3 h (for cell apoptosis and oxidative/nitrative stress), 24 h (for infarct size and cardiac function), or 2 weeks (for cardiac fibrosis and function) of reperfusion. Cardiac-specific Notch1 knockdown resulted in significantly aggravated I/R injury, as evidenced by enlarged infarct size, depressed cardiac function, increased myocardial apoptosis and cardiac fibrosis. Downregulation of Notch1 increased expression of inducible NO synthase (iNOS) and gp(91phox), enhanced the production of NO metabolites and superoxide, as well as their cytotoxic reaction product peroxynitrite. Moreover, Notch1 blockade also reduced phosphorylation of endothelial NO synthase (eNOS) and Akt, and increased expression of PTEN, a key phosphatase involved in the regulation of Akt phosphorylation. In addition, activation of Notch1 by Jagged1 or administration of peroxynitrite scavenger reduced production of peroxynitrite and attenuated MI/R injury. These data indicate that Notch1 signaling protects against MI/R injury partly though PTEN/Akt mediated anti-oxidative and anti-nitrative effects.

Impaired mitochondrial biogenesis causes skeletal muscle damage in diabetes. However, whether and how mitochondrial biogenesis is impaired in the diabetic heart remains largely unknown. Whether adiponectin (APN), a potent cardioprotective molecule, regulates cardiac mitochondrial function has also not been previously investigated. In this study, electron microscopy revealed significant mitochondrial disorders in ob/ob cardiomyocytes, including mitochondrial swelling and cristae disorientation and breakage. Moreover, mitochondrial biogenesis of ob/ob cardiomyocytes is significantly impaired, as evidenced by reduced Ppargc-1a/Nrf-1/Tfam mRNA levels, mitochondrial DNA content, ATP content, citrate synthase activity, complexes I/III/V activity, AMPK phosphorylation, and increased PGC-1α acetylation. Since APN is an upstream activator of AMPK and APN plasma levels are significantly reduced in ob/ob mice, we further tested the hypothesis that reduced APN in ob/ob mice is causatively related to mitochondrial biogenesis impairment. One week of APN treatment of ob/ob mice activated AMPK, reduced PGC-1α acetylation, increased mitochondrial biogenesis, and attenuated mitochondrial disorders. In contrast, knocking out APN inhibited AMPK-PGC-1α signaling and impaired both mitochondrial biogenesis and function. The ob/ob mice exhibited lower survival rates and exacerbated myocardial injury after MI, when compared to controls. APN supplementation improved mitochondrial biogenesis and attenuated MI injury, an effect that was almost completely abrogated by the AMPK inhibitor compound C. In high glucose/high fat treated neonatal rat ventricular myocytes, siRNA-mediated knockdown of PGC-1α blocked gAd-enhanced mitochondrial biogenesis and function and attenuated protection against hypoxia/reoxygenation injury. In conclusion, hypoadiponectinemia impaired AMPK-PGC-1α signaling, resulting in dysfunctional mitochondrial biogenesis that constitutes a novel mechanism for rendering diabetic hearts more vulnerable to enhanced MI injury.

Objectives Evidence exists that the increase of TNFα is associated with reperfusion injury in patients with myocardial infarction after PCI. Adiponectin (APN) is anti-inflammatory and cardioprotective protein suppressed by TNFα, and is significantly reduced during MI/R. Whether neutralising TNFα protects against MI/R injury through upregulation of APN level has not been previously investigated. Methods and Results Adult male C57 mice were subjected to 30 min MI followed by 3h or 24h reperfusion or sham MI/R for this study. Etanercept, a TNFα neutralising drug for treating rheumatoid arthritis in clinic, was intraperitoneally injected 10 min before reperfusion. Etanercept administration ameliorated MI/R injury evidenced by increased cardiac function (1 day, 7 day, 14 day p Conclusions Overall, we have demonstrated for the first time that upregulating of adiponectin is involved in the cardioprotective effect of Etanercept, suggesting that using a single administration of Etanercept during PCI might improve the outcome of myocardial infarction patients.