Qishen Granule alleviates endoplasmic reticulum stress-induced myocardial apoptosis through IRE-1-CRYAB pathway in myocardial ischemia.

摘要: Abstract Ethnopharmacological relevance Qishen Granule (QSG) is a prevailing traditional Chinese medicine formula that displays impressive cardiovascular protection in clinical. However, underlying mechanisms by which QSG alleviates endoplasmic reticulum (ER) stress-induced apoptosis myocardial ischemia still remain unknown. Aim of the study This aims to elucidate whether ameliorates ER protect against via inositol requiring enzyme 1 (IRE-1)-αBcrystallin (CRYAB) signaling pathway. Materials and methods Left anterior descending (LAD) ligation induced-ischemic heart model oxygen-glucose deprivation-reperfusion (OGD/R)-induced H9C2 cells injury were established clarify effects potential mechanism QSG. Ethanol extracts (2.352 g/kg) orally administered for four weeks Ginaton Tablets (100 mg/kg) was selected as positive group vivo. In vitro, (800 μg/ml) or STF080310 (an inhibitor IRE-1, 10 μM) co-cultured under OGD/R cells. Inhibition IRE-1 conducted further confirm exact mechanism. Finally, define active components anti-cardiomyocyte absorbed into blood, we furtherly used OGD/R-induced cardiomyocyte evaluate effects. Results treatment improved cardiac function, ameliorated inflammatory cell infiltration apoptosis. Similar revalidated model. Western blots demonstrated exerted anti-apoptotic regulating apoptosis-related proteins, including increasing Bcl-2 caspase 3/12, reducing expressions Bax cleaved-caspase 3/12. Mechanistically, IRE-1-CRYAB pathway significantly activated Co-treatment with STF080310, specific compromised protective vitro. Especially, Formononetin, Tanshinone IIA, I, Cryptotanshinon Harpagoside showed anti-apoptosis Conclusion protected pathway, proposed promising therapeutic target ischemia.