Background/Aims: Ischemia-reperfusion (I/R) injury is believed to be the major cause for detriments in coronary heart diseases, but few effective therapies for prevention or treatment of I/R injury are available. Gypenoside (GP) is the predominant effective component of Gynostemma pentaphyllum and possesses capacities against inflammation and oxidation. In the present study, the role of GP in ameliorating myocardial I/R injury was investigated. Methods: effect GP on the cardiac structure of I/R injured rats was assessed by H&E and TTC staining. Then the influence of GP on the cardiac function of rat model was determined by measuring hemodynamics parameters, levels of lactate dehydrogenase (LDH) and creatine kinase (CK). Thereafter, effect of GP on apoptotic process was evaluated with both rat and cell models. The production of molecules related to ER stress and apoptosis was quantified for revelation of pathways involved in the myocardial protective effect of GP. Results: Impairments in cardiac structure due to I/R injury was ameliorated by GP treatment. And it was evidently demonstrated that administration of GP not only effectively decreased the apoptotic rates in both rat and cell models but also markedly improved the cardiac function of I/R injured rats. In addition, results of western blotting revealed that the GP inhibited ER-stress and apoptosis through the blockade of CHOP pathway and activation of PI3K/Akt pathway. Conclusion: the current study showed the potential of GP to alleviate myocardial I/R injury and preliminarily uncovered the underling mechanism driving this treatment.

Gypenosides (GP) are the predominant components of Gynostemma pentaphyllum, a Chinese herb medicine that has been widely used for the treatment of chronic inflammation, hyperlipidemia, and cardiovascular disease. GP has been demonstrated to exert protective effects on the liver and brain against ischemia-reperfusion (I/R) injury, yet whether it is beneficial to the heart during myocardial I/R is unclear. In this study, we demonstrate that pre-treatment with GP dose-dependently limits infarct size, alleviates I/R-induced pathological changes in the myocardium, and preserves left ventricular function in a rat model of cardiac I/R injury. In addition, GP pre-treatment reduces oxidative stress and protects the intracellular antioxidant machinery in the myocardium. Further, we show that the cardioprotective effect of GP is associated with the preservation of mitochondrial function in the cardiomyocytes, as indicated by ATP level, enzymatic activities of complex I, II, and IV on the mitochondrial respiration chain, and the activity of citrate synthase in the citric acid cycle for energy generation. Moreover, GP maintains mitochondrial membrane integrity and inhibits the release of cytochrome c from the mitochondria to the cytosol. The cytoprotective effect of GP is further confirmed in vitro in H9c2 cardiomyoblast cell line with oxygen-glucose deprivation and reperfusion (OGD/R), and the results indicate that GP protects cell viability, reduces oxidative stress, and preserves mitochondrial function. In conclusion, our study suggests that GP may be of clinical value in cytoprotection during acute myocardial infarction and reperfusion.

Gypenoside (GP) is the major effective component of Gynostemma pentaphyllum and has been shown to encompass a variety of pharmacological activities. In this study, we investigated whether GP is able to protect cardiomyocytes against injury myocardial ischemia–reperfusion (I/R) injury by using in vitro oxygen-glucose deprivation–reoxygenation (OGD/R) H9c2 cell model and in vivo myocardial I/R rat model. We found that GP pre-treatment alleviated the impairments on the cardiac structure and function in I/R injured rats. Moreover, pre-treatment with GP significantly inhibited IκB-α phosphorylation and nuclear factor (NF)-κB p65 subunit translocation into nuclei. GP and the MAPK pathway inhibitors also reduced the phosphorylation of ERK, JNK, and p38 in vitro. Specific inhibition of ERK, JNK, and p38 increased the cell viability of OGD/R injured cells. Taken together, our data demonstrated that GP protects cardiomyocytes against I/R injury by inhibiting NF-κB p65 activation via the MAPK signaling pathway both in vitro and in vivo. These findings suggest that GP may be a promising agent for the prevention or treatment of myocardial I/R injury.

Triptolide is a bioactive component of Chinese herbal plant Tripterygium wilfordii Hook F that has recently been noted to attenuate hepatic and cerebral ischemia/reperfusion (I/R) injuries in rodents. To investigate whether triptolide could protect against myocardial I/R injuries, triptolide (25, 50 or 100 μg/kg) was administrated in Wistar rats that underwent left anterior descending coronary artery ligation in this study. Our data showed that triptolide pretreatment could attenuate myocardial infarction, increase the fractional shortening and left ventricular systolic pressure and decrease the left ventricular end-diastolic pressure in ischemic rats. Also, triptolide was noted to inhibit the activities of lactate dehydrogenase and creatine kinase in I/R rats. Moreover, triptolide administration suppressed macrophage infiltration, inhibited the overproduction of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and malondialdehyde (MDA) in reperfused myocardium tissues and upregulated the activities of antioxidative superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GPx). In addition, nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the activity of its downstream target Heme oxygenase-1 (HO-1) in ischemic myocardium tissues were enhanced by triptolide pretreatment. In addition, the HO-1 inhibitor, zinc protoporphyrin-IX, abrograted the cardiac protection mediated by triptolide. Our study reveals a novel cardioprotective effect of triptolide in rats with I/R injuries, wherein the activation of Nrf2/HO-1 signaling was involved.

Background/AimsGastrointestinal (GI) symptoms may develop when we fail to adapt to various stressors of our daily life. Central oxytocin (OXT) can counteract the biological actions of corticotropin-releasing factor (CRF), and in turn attenuates stress responses. Administration (intracerebroventricular) of OXT significantly antagonized the inhibitory effects of chronic complicated stress (CCS) on GI dysmotility in rats. However, intracerebroventricular administration is an invasive pathway. Intranasal administration can rapidly deliver peptides to the brain avoiding stress response. The effects of intranasal OXT on hypothalamus-pituitary-adrenal axis and GI motility in CCS conditions have not been investigated.Methods A CCS rat model was set up, OXT 5, 10, or 20 μg were intranasal administered, 30 minutes prior to stress loading. Central CRF and OXT expression levels were analyzed, serum corticosterone and OXT concentrations were measured, and gastric and colonic motor functions were evaluated by gastric emptying, fecal pellet output, and motility recording system. ResultsRats in CCS condition showed significantly increased CRF expression and corticosterone concentration, which resulted in delayed gastric emptying and increased fecal pellet output, attenuated gastric motility and enhanced colonic motility were also recorded. OXT 10 μg or 20 μg significantly reduced CRF mRNA expression and the corticosterone concentration, OXT 20 μg also helped to restore GI motor dysfunction induced by CCS. ConclusionIntranasal administration of OXT has an anxiolytic effect and attenuates the hypothalamus-pituitary-adrenal axis in response to CCS, and gave effects which helped to restore GI dysmotility, and might be a new approach for the treatment of stress-induced GI motility disorders. Motil 2019;25:611-622) (J Neurogastroenterol