Cardioprotective effect of notoginsenoside R1 in a rabbit lung remote ischemic postconditioning model via activation of the TGF-ß1/TAK1 signaling pathway.

Pharmacological postconditioning using cardioprotective agents is able to reduce myocardial infarct size. Notoginsenoside R1 (NG-R1), a phytoestrogen isolated from Panax notoginseng saponins (PNS), is considered to have anti-oxidative and anti-apoptotic properties. However, its cardioprotective properties and underlying mechanisms remain largely unknown. The aim of the present study was to determine the cardioprotective and anti-apoptotic effects of NG-R1 in an ischemia-reperfusion (IR)-induced myocardial injury rabbit model. A total of 45 Japanese big-ear rabbits were equally randomized to three groups: Control group, remote ischemic postconditioning (RIP) group and NG-R1 intervention group. At the endpoint of the experiment, the animals were sacrificed to remove myocardial tissues for the detection of transforming growth factor (TGF)-ß1-TGF-ß activated kinase 1 (TAK1) pathway-related proteins by immunohistochemistry and western blot analysis, the activities of caspase-3, -8 and -9 in myocardial cells by fluorometric assay, and the apoptosis of myocardial cells by terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling. Right and left lung tissues were stained with hematoxylin and eosin (H&E) to observe the severity of injury. NG-R1 treatment reduced the activity of superoxide dismutase, increased the content of malondialdehyde, reduced the activities of caspase-3, -8 and -9, and inhibited the apoptosis of myocardial cells in rabbits undergoing RIP. In addition, the expression of TGF-ß1-TAK1 signaling pathway-related proteins was downregulated following NG-R1 intervention. H&E staining of bilateral lung tissues showed that cell morphology was generally intact without significant alveolar congestion, and there was no significant difference among the three groups. These results indicate that NG-R1 protects the heart against IR injury, possibly by inhibiting the activation of the TGF-ß1-TAK1 signaling pathway and attenuating apoptotic stress in the myocardium.

miR-103 Regulates Oxidative Stress by Targeting the BCL2/Adenovirus E1B 19 kDa Interacting Protein 3 in HUVECs.

Oxidative stress plays a critical role in cardiovascular diseases. Salidroside, a glycoside from Rhodiola rosea, has been used as an antioxidative therapy for oxidative injury in cardiac diseases. However, the mechanism underlying its antioxidant effect needs to be elucidated. Treatment of HUVECs with H2O2 significantly decreased the expression of miR-103 in a dose- and time-dependent manner, whereas pretreatment with salidroside significantly inhibited this decrease. Subsequent analysis showed that overexpression of miR-103 abrogated cell activity and ROS production induced by H2O2. Bcl2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) was determined to be a novel miR-103 target in HUVECs. Interestingly, H2O2 treatment upregulated BNIP3 expression; in turn, this effect was inhibited by pretreatment with salidroside. Further studies confirmed that the knockdown of BNIP3 enhanced cell activity and suppressed the ROS production induced by H2O2. These results demonstrated for the first time that salidroside protects HUVECs in part by upregulating the expression of miR-103, which mediates BNIP3 downregulation and plays an important role in the cytoprotective actions.

Pressure overload-induced cardiac hypertrophy response requires janus kinase 2-histone deacetylase 2 signaling.

Pressure overload induces cardiac hypertrophy through activation of Janus kinase 2 (Jak2), however, the underlying mechanisms remain largely unknown. In the current study, we tested whether histone deacetylase 2 (HDAC2) was involved in the process. We found that angiotensin II (Ang-II)-induced re-expression of fetal genes (Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)) in cultured cardiomyocytes was prevented by the Jak2 inhibitor AG-490 and HDAC2 inhibitor Trichostatin-A (TSA), or by Jak2/HDAC2 siRNA knockdown. On the other hand, myocardial cells with Jak2 or HDAC2 over-expression were hyper-sensitive to Ang-II. In vivo, pressure overload by transverse aorta binding (AB) induced a significant cardiac hypertrophic response as well as re-expression of ANP and BNP in mice heart, which were markedly reduced by AG-490 and TSA. Significantly, AG-490, the Jak2 inhibitor, largely suppressed pressure overload-/Ang-II-induced HDAC2 nuclear exportation in vivo and in vitro. Meanwhile, TSA or HDAC2 siRNA knockdown reduced Ang-II-induced ANP/BNP expression in Jak2 over-expressed H9c2 cardiomyocytes. Together, these results suggest that HDAC2 might be a downstream effector of Jak2 to mediate cardiac hypertrophic response by pressure overload or Ang-II.

Salidroside protects against hydrogen peroxide-induced injury in HUVECs via the regulation of REDD1 and mTOR activation.

Antioxidative therapy is considered an effective strategy for treating oxidative stress-induced apoptosis in cardiovascular diseases. Salidroside has been used as an antioxidative therapy for oxidative injury in cardiac diseases. However, the mechanism underlying its antioxidant effect is poorly understood. The present study aimed to investigate the pharmacological effects of salidroside on cultured human umbilical vein endothelial cells (HUVECs) under conditions of oxidative injury induced by hydrogen peroxide (H2O2) and the underlying mechanisms in vitro. HUVECs pretreated with or without salidroside for 24 h were exposed to H2O2-induced oxidative stress conditions for 6 h and then cell viability, apoptosis, HIF-1α, regulated in development and DNA damage responses-1 (REDD1) and the PI3K/Akt/mTOR pathway were investigated. The results demonstrated that salidroside effectively attenuated H2O2-impaired cell viability and the production of reactive oxygen species (ROS) in a concentration-dependent manner. Reduced H2O2-induced apoptosis and activation of the cellular PI3K/Akt/mTOR pathway were demonstrated in HUVECs pretreated with salidroside. Furthermore, the level of REDD1, a direct regulator of mitochondrial metabolism, significantly increased in parallel with the level of HIF-1α following pretreatment with salidroside. The antioxidative effect of salidroside was abrogated in REDD1 knockdown cells. However, LY294002, a PI3K inhibitor, attenuated the anti-apoptotic effect of salidroside and blocked the increase of Akt and mTOR; however, did not affect the antioxidative effect of salidroside. These findings suggested that salidroside was capable of protecting HUVECs against H2O2-induced apoptosis by activating the PI3K/Akt/mTOR-dependent pathway and inhibiting ROS production by activating REDD1.

Salidroside attenuates myocardial ischemia-reperfusion injury via PI3K/Akt signaling pathway.

To investigate the cardioprotective effects of salidroside on myocardial ischemia-reperfusion injury (IRI) in rabbits and the underlying action mechanisms in PI3K/Akt signaling pathway, a rabbit ischemia/reperfusion model was created by ligating the left anterior descending coronary arterial branch for 30 min and by releasing the ligature to allow reperfusion for 120 min. Salidroside or salidroside+PI3K inhibitor (LY294002) was administered via intracoronary injections at the onset of reperfusion. Apoptosis of cardiomyocytes was assessed by terminal dUTP nick-end labeling assay, and the expression of apoptosis-related proteins was observed by immunohistochemistry. The expressions of total Akt and phosphorylated Akt (p-Akt) were detected by western blot analysis. The results showed that intracoronary injection of salidroside at the onset of reperfusion markedly reduced the apoptosis of cardiomyocytes, significantly increasing Bcl-2 and p-Akt proteins expressions and decreasing Bax and caspase-3 expressions in the hearts subjected to ischemia followed by 120-min reperfusion. However, the anti-apoptotic effect induced by salidroside was inhibited by LY294002, which blocked the activation of Akt. These results suggested that intracoronary administration of salidroside at the onset of reperfusion could significantly reduce the IRI-induced apoptosis of cardiomyocytes, and this protective mechanism seemed to be mediated by the PI3K-Akt signaling pathway.

[Diagnostics of atmospheric-pressure radio-frequency capacitively coupled Ar/N2 plasma by optical emission spectroscopy].

An atmospheric-pressure Ar/N2 glow discharge was achieved in a mode stricken between bare metal plate electrodes by radio-frequency power supply at 13.56 MHz. The rotational temperature was determined by using the Boltzmann plot of the OH (A 2sigma+ --> X 2pi) radical and the variation tendency of the gas temperature versus the input power was obtained. Furthermore, the measurement of the sequences of vibrational bands of N2 second positive system (C 3 pi(u) --> B 3 pi(g)) is made and the vibrational temperature was determined correspondingly. The experiment results showed that the emission peaks of N2 (C3 pi(u)) reached the maximum at the nitrogen flow rate of 80 mL x min(-1) with increasing addition of nitrogen, the gas temperature increased from 342 to 523 K when the input power increased from 30 to 210 W, and the vibrational temperature changed slightly when the gas flow rate of nitrogen increased from 30 to 140 mL x min(-1).