Protective effect of saponins extract from Panax japonicus on myocardial infarction: involvement of NF-κB, Sirt1 and mitogen-activated protein kinase signalling pathways and inhibition of inflammation.

Inflammation is widely acknowledged to increase morbidity and mortality in myocardial infarction (MI), and the ideal therapeutic methods should be aimed at the inflammation reaction triggers. The aim was to evaluate the protective effect of saponins extracted from Panax japonicus (SPJ) on MI, and based on these results investigate the possible involvement mechanism of the nuclear factor-kappa B (NF-κB), sirtuin1 (SIRT1) and mitogen-activated protein kinases (MAPKs) signalling pathways. Sprague-Dawley rats were randomly divided into sham, MI, MI + SPJ 50 and SPJ 100 mg/kg groups. After administration for 3 days, MI rats were created by ligaturing coronary artery, and then underwent the same administration for 7 days as before. Cardiac function and the expressions of pro-apoptosis protein Bax, anti-apoptosis protein Bcl-2, NF-κB, SIRT1, MAPKs signal pathway-related proteins and inflammatory factor, such as tumour necrosis factor alpha (TNF-α) and monocyte chemoattractant protein 1 (MCP-1), were assessed. SPJ might significantly improve cardiac function, decrease the serum MCP-1 and TNF-α levels, ameliorate the increased Bax protein expression and decrease Bcl-2 protein expression, and suppress the protein expressions of NF-κBp65 subunit, extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 MAPK, but have no effect on c-Jun NH2-terminal kinase, and increase the expression of SIRT1. Histopathological observations provided supportive evidence for aforementioned results, and with the dose of SPJ increasing, the aforesaid improvement became more and more strong. The studies demonstrated that SPJ exerted beneficially cardioprotective effects on MI rats, mainly inhibiting NF-κB, ERK1/2 and p38 MAPK activation, but increased the expression of SIRT1, alleviating MI injury and cardiac cell death.

Wei N ，Zhang C ，He H ，Wang T ，Liu Z ，Liu G ，Sun Z ，Zhou Z ，Bai C ，Yuan D ... -  《-》

Cardioprotective effects of saponins from Panax japonicus on acute myocardial ischemia against oxidative stress-triggered damage and cardiac cell death in rats.

To study the cardioprotective effects of saponins from Panax japonicus (SPJ) on acute myocardial ischemia injury rats induced by ligating of the left anterior descending branch (LAD), on the basis of this investigation, the possible mechanism of SPJ was elucidated. SPJ was identified by high performance liquid chromatography-evaporative light scattering detection. Male Sprague-Dawley rats (200-220g) were randomly divided into four groups: sham-operated, LAD, LAD+l-SPJ (SPJ, 50mg/kg/day, orally) and LAD+h-SPJ (SPJ, 100mg/kg/day, orally). Before operation, the foregoing groups were pretreated with homologous drug once a day for 7 days, respectively. After twelve hours in LAD, the cardioprotective effects of SPJ were evaluated by infarct size, biochemical values, hemodynamic, and histopathological observations and the antioxidative and antiapoptotic relative gene expressions. SPJ significantly improved heart function and decreased infarct size; remarkably decreased levels of serum lactate dehydrogenase, creatine kinase, xanthine oxide and malondialdehyde content, increased contents of serum total antioxidant capacity, superoxide dismutase (SOD), glutathione peroxidase, catalase; quantitative real-time PCR results showed that SPJ might markedly reverse the down-regulated mRNA expressions of the SOD1, SOD2 and SOD3, ameliorate the increased Bax and caspase-3 mRNA expressions and decreased Bcl-2 mRNA expression and ratios of Bcl-2 to Bax. Histopathological observations provided supportive evidence for biochemical analyses, and with the dose of SPJ increasing, the aforesaid improvement became more and more strong. The studies demonstrated that in ischemic myocardium, oxidative stress caused the overgeneration and accumulation of reactive oxygen species (ROS), which was central of cardiac ischemic injury. SPJ exerted beneficially cardioprotective effects on myocardial ischemia injury rats, mainly scavenging oxidative stress-triggered overgeneration and accumulation of ROS, alleviating myocardial ischemia injury and cardiac cell death.

He H ，Xu J ，Xu Y ，Zhang C ，Wang H ，He Y ，Wang T ，Yuan D ... -  《-》

[Effect of saponins extracted from Panax japonicus on inhibiting cardiomyocyte apoptosis by AMPK/Sirt1/NF-κB signaling pathway in aging rats].

To investigate the effects of saponins extracted from Panax japonicus(SPJ) on cardiomyocyte apoptosis in natural aging rats and explore its underlying mechanisms. SD male rats were randomly divided into four groups: young control group, natural aging group, SPJ low dose group and SPJ high dose group, with 10 rats in each group. The rats in natural aging group, SPJ low and high dose groups were respectively treated with normal saline, SPJ 10 and 60 mg•kg-1•d-1 from the beginning of 18 month-old, 6 days per week for 6 months till 24 month-old. Then the animals were sacrificed. Their myocardial morphology changes were observed by using haematoxylin-eoin(HE) staining; cardiomyocyte apoptosis was tested by using Tunel assays; and the protein expression levels of Bcl-2, Bax, IL-1β, TNF-α, AMPK, p-AMPK, Sirt1, and Ac-NF-κB p65 in myocardial tissues of rats were detected by Western blot. The results showed that SPJ could effectively improve the arrangement disorder of myocardial fibers, reduce the infiltration of inflammatory cells and inhibit cardiomyocyte apoptosis in natural aging rats. At the same time, SPJ could significantly inhibit the protein expression of Bax, IL-1β, TNF-α and Ac-NF-κB p65, and increase the expression of Bcl-2, Bcl-2/Bax, p-AMPK/AMPK and Sirt1 in the heart tissues of natural aging rats. SPJ can effectively inhibit cardiomyocyte apoptosis in natural aging rats, and its mechanisms may be related with the regulation of inflammatory reaction by AMPK/Sirt1/NF-κB signaling pathway.

Song YN ，Yuan D ，Zhang CC ，Wang LP ，He YM ，Wang T ，Zhou ZY ... -  《-》

Panax Notoginseng Saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NF κ B Pathway.

Ma RF ，Chen G ，Li HZ ，Zhang Y ，Liu YM ，He HQ ，Liu CY ，Xie ZC ，Zhang ZP ，Wang J ... -  《-》

Sophocarpine administration preserves myocardial function from ischemia-reperfusion in rats via NF-κB inactivation.

Li C ，Gao Y ，Tian J ，Shen J ，Xing Y ，Liu Z ... -  《-》