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Background/aims: A series of reports revealed that autophagy and apoptosis exerted detrimental effects on the pathology of cardiac ischemia/reperfusion (I/R) injury. Ginsenoside compound K (CK), a major intestinal metabolite underlying the pharmacological actions of orally administered ginseng, has a protective effect against myocardial I/R injury. However, the molecular mechanisms by which CK protects against I/R injury remain unclear. In this study, we hypothesized that the cardioprotective effects of CK against I/R injury are mediated by inhibiting autophagy/apoptosis-related signaling pathways in H9c2 cardiomyocyte cells., Methods: H9c2 cells were incubated with CK and exposed to I/R. Cell viability and damage was analyzed by MTT and lactate dehydrogenase assays. Reactive oxygen species (ROS) generation, mitochondrial damage, and cell apoptosis were analyzed by flow cytometry and TUNEL staining. The expression of autophagy, apoptosis, and related signaling proteins was analyzed by Western blotting and immunofluorescence staining., Results: CK pretreatment promoted cell viability and attenuated ROS accumulation and intracellular mitochondrial damage induced by I/R injury Moreover, CK reduced autophagy by regulating the formation of phagocytic precursors to autophagosomes and also inhibited apoptosis through a mitochondrial-mediated pathway. Additionally the cardioprotective effect of CK against I/R injury was mainly through the activation of the PI3K-Akt signaling pathway., Conclusions: CK pretreatment inhibits autophagy-mediated apoptosis induced by I/R injury through the activation of the PI3K-Akt signaling pathway, which reveals that CK may be one of the key bioactive ingredients of ginseng for the treatment of myocardial I/R injury., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Oxygen and glucose deprivation and reperfusion (OGD/R) injury contributes to the pathophysiology after ischemic stroke, which needs to urgently develop treatment strategies. Previous studies have demonstrated that autophagy in reperfusion period exerted adverse effects on the cerebral ischemic injury. Ginsenoside monomer compound K (CK) is the main intestinal metabolite of ginseng that exerts the pharmacological activities and has a protective effect against cerebral OGD/R injury. However, the specific molecular mechanism of CK protects against OGD/R injury in neurons is still unclear. In this study, cell viability, reactive oxygen species (ROS) generation, Ca2+ overload, mitochondrial membrane potential depolarization, autophagy and apoptosis were investigated in OGD/R-induced neuronal cells injury after pretreatment with CK and in combination with BML-275 or rapamycin. Our study found that pretreatment with CK protected neurons against OGD/R injury by increasing cell viability and decreasing the ROS generation, mitochondrial damage, and Ca2+ overload. Moreover, CK cut down autophagy-mediated apoptosis via promoting the process of forming autophagosomes into phagocytic precursors. Furthermore, our study clarified the neuroprotective of CK against OGD/R-induced neural autophagy and apoptosis through the regulation of the AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathway. Taken together, our study provides credible experimental evidence and explains the potential molecular mechanism of CK as one of the main bioactive ingredients of ginseng for the treatment of cerebral ischemia/reperfusion injury. Unlabelled Image • Compound K decreased the ROS generation, mitochondrial damage and Ca2+ overload. • Compound K reduced apoptosis and autophagy by regulating the formation of phagocytic precursors to autophagosomes. • Compound K regulated the AMPK-mTOR pathway in OGD/R-induced neuronal cells injury. • Compound K is the key bioactive ingredients of ginseng for the treatment of cerebral ischemia stoke. [ABSTRACT FROM AUTHOR]

ZhiShiXiaoPi Tang (ZSXPT) is a Chinese traditional medicine formula that contains 10 Chinese traditional medicine substances. It has been widely used to treat patients with functional dyspepsia (FD). However, the protective effect of ZSXPT and its molecular mechanisms in FD still remain elusive. To investigate the protective effect of ZSXPT on autophagy induced by Corticosterone (Cort) in PC12 cells which have typical neuron characteristics and have been widely used as a model system for depression studies and FD rats, and explore its underlying mechanisms. In this study, high-performance liquid chromatography fingerprint analysis was performed to characterize the chemical composition of ZSXPT. Depression-induced autophagy, ROS generation, and changes in mitochondrial membrane potential (MMP) were investigated in Cort-induced PC12 cells and in FD rats to evaluate the protective effects of ZSXPT. Our results show that ZSXPT treatment protects neurons against Cort-induced damage and apoptosis by increasing cell viability and reducing the release of lactate dehydrogenase. ZSXPT decreased Cort-induced ROS generation, increased MMP, and accelerated autophagy through the blockade of the mammalian target of rapamycin (mTOR) pathway. Moreover, we observed similar findings when we studied ZSXPT in a rat model of FD. Our in vitro and in vivo results indicate that the neuroprotective effect of ZSXPT against autophagy-induced damage and apoptosis occurs mainly by blocking the mTOR pathway in Cort-induced PC12 cells and in FD rats. Taken together, these data provide reliable experimental evidence and explain the molecular mechanism by which ZSXPT ameliorates FD. Image 1 [ABSTRACT FROM AUTHOR]