Panax quinquefolium saponin attenuates cardiomyocyte apoptosis and opening of the mitochondrial permeability transition pore in a rat model of ischemia/reperfusion.

Opening of the mitochondrial permeability transition pore (mPTP) is a critical event during ischemia/reperfusion (I/R) injury. Recently, we showed that Panax quinquefolium saponin (PQS) alleviates apoptosis of cardiomyocytes by suppressing excessive endoplasmic reticulum stress (ERS) during I/R injury. Here, we hypothesized that this anti-apoptotic effect might be mediated through inhibition of mPTP and the mitochondrial apoptotic pathway. Ninety-six healthy male Sprague-Dawley rats were randomly divided into sham, I/R, I/R+PQS (200 mg/kg/d), Cyclosporine A (CsA, 10 mg/kg), I/R+CsA (10 mg/kg), and I/R+PQS+CsA. I/R was modeled in rats by ligating the left anterior descending artery (LAD) for 30 min followed by 120 min of reperfusion. To evaluate the cardioprotective function of PQS, we measured hemodynamics, serum content of creatine kinase-MB (CK-MB), myocardial infarct size, and myocardial apoptotic index (AI). We investigated the underlying mechanism by examining changes in the mitochondrial ultrastructure and membrane potential (ΔΨm), dynamics of mPTP opening, expression of cleaved caspase-3, cleaved caspase-9 in the myocardium, Bcl-2 and Bax in the mitochondria versus cytosol, and translocation of cytochrome c. Administration of PQS to I/R rats significantly reduced serum CK-MB level, infarct size and AI. In addition, PQS protected the mitochondrial structure, markedly inhibited mPTP opening and ΔΨm depolarization, led to upregulation of Bcl-2 and downregulation of Bax in the mitochondria compared to the cytosol, and suppressed the expression of cleaved caspase-9 and cleaved caspase-3, as well as I/R induced translocation of cytochrome c to the cytoplasm. Our results show that PQS can alleviate apoptosis of cardiomyocytes during I/R injury, possibly due to repressed mitochondrial apoptotic pathway associated with the opening of mPTP induced by myocardial I/R injury.

Li D ，Liu M ，Tao TQ ，Song DD ，Liu XH ，Shi DZ ... -  《-》

Clematichinenoside (AR) Attenuates Hypoxia/Reoxygenation-Induced H9c2 Cardiomyocyte Apoptosis via a Mitochondria-Mediated Signaling Pathway.

Ding H ，Han R ，Chen X ，Fang W ，Liu M ，Wang X ，Wei Q ，Kodithuwakku ND ，Li Y ... -  《MOLECULES》

Nutritional preconditioning induced by astragaloside Ⅳ on isolated hearts and cardiomyocytes against myocardial ischemia injury via improving Bcl-2-mediated mitochondrial function.

Ischemic preconditioning and pharmacological preconditioning are common strategies to prevent lethal myocardial injury, especially nutritional preconditioning (NPC). In this study, we investigated the effects of astragaloside IV (Ast), as an NPC agent, on myocardium suffered anoxia/reoxygenation (A/R) injury. Rats received 5 mg/kg Ast daily for 3 weeks by intragastric administration. Then, hearts were harvested and underwent A/R treatment using a Langendorff apparatus. Ast- pretreatment significantly promoted functional recovery of the myocardium, reduced infarct size, and oxidative stress, and decreased the apoptotic index. Similar findings were demonstrated in H9c2 cardiomyocytes that were pretreated with Ast for 24 h. Moreover, Ast-pretreatment significantly upregulated Bcl-2 expression, especially in mitochondria. The effects of Ast treatment against A/R injury were also reflected by increased antioxidant potential, inhibited reactive oxygen species (ROS) burst, increased oxygen consumption rate, maintained mitochondrial membrane potential (MMP), inhibited mitochondrial permeability transition pore (mPTP) opening, and prevented apoptosis. Selective inhibition of Bcl-2 by ABT-737 decreased myocardial injury protection of Ast. Ast-pretreatment resulted in NPC- related effects against A/R, and mitochondria may be the target of a cascade of events elicited by upregulating Bcl-2 expression, promoting translocation of Bcl-2 into mitochondria, maintaining MMP, inhibiting ROS bursts, thereby leading to recovery of mitochondrial respiration, preventing mPTP opening, decreasing cytochrome C release, preventing apoptosis, and ultimately alleviating myocardial injury.

Luo Y ，Wan Q ，Xu M ，Zhou Q ，Chen X ，Yin D ，He H ，He M ... -  《-》

Febuxostat pretreatment attenuates myocardial ischemia/reperfusion injury via mitochondrial apoptosis.

Wang S ，Li Y ，Song X ，Wang X ，Zhao C ，Chen A ，Yang P ... -  《Journal of Translational Medicine》

Curculigoside attenuates myocardial ischemia‑reperfusion injury by inhibiting the opening of the mitochondrial permeability transition pore.

Zhao Y ，Guo Y ，Chen Y ，Liu S ，Wu N ，Jia D ... -  《-》