Cardioprotective effect exerted by Timosaponin BⅡ through the regulation of endoplasmic stress-induced apoptosis.

Background: Timosaponin BⅡ (TBⅡ), one of the primary bioactive compounds from Anemarrhena asphodeloides Bunge, possesses potential cardioprotective effects. However, the mechanism underlying TBⅡ-mediated cardioprotection, especially the involvement of endoplasmic reticulum stress, remains largely unknown.

Purpose: This study was designed to evaluate the role of TBⅡ in myocardial injury protection and explore its possible mechanisms.

Methods: In vivo models of isoproterenol-induced myocardial injury and HO-induced cytotoxicty were established to investigate the effect of anti-myocardial injury of TBⅡ. The potential mechanisms were investigated in vitro and in vivo using multiple detection methods like electrocardiography, histo-pathological examination, JC-1 staining, TUNEL staining, ELISA technology, and western blot analysis.

Results: In vivo study revealed that TBⅡ improved electrocardiography and heart vacuolation, reduced myocyte apoptosis, and improved the antioxidant potential. In vitro investigation demonstrated that TBⅡ pretreatment inhibited ER stress-mediated apoptosis pathways. Further investigation of the underlying mechanisms revealed that TBⅡ prevented HO-induced H9c2 cardiomyocytes injury by the PI3K/Akt pathways, whereas the addition of LY294002, the pharmacologic antagonist of PI3K, attenuated TBⅡ-induced expression of apoptotic protein and cytoprotective effects.

Conclusion: These results suggested that TBⅡ protects against myocardial injury in vitro and enhances cellular defense capacity by inhibiting ER stress-mediated apoptosis pathways in vivo by activating the PI3K/Akt pathways.