Cardioprotection by combination of three compounds from ShengMai preparations in mice with myocardial ischemia/reperfusion injury through AMPK activation-mediated mitochondrial fission

Abstract

GRS is a drug combination of three active components including ginsenoside Rb1, ruscogenin and schisandrin. It derived from the well-known TCM formula ShengMai preparations, a widely used traditional Chinese medicine for the treatment of cardiovascular diseases in clinic. The present study explores the cardioprotective effects of GRS on myocardial ischemia/reperfusion (MI/R) injury compared with ShengMai preparations and investigates the underlying mechanisms. GRS treatment significantly attenuated MI/R injury and exhibited similar efficacy as Shengmai preparations, as evidenced by decreased myocardium infarct size, ameliorated histological features, the decrease of LDH production and improved cardiac function, and also produced a significant decrease of apoptotic index. Mechanistically, GRS alleviated myocardial apoptosis by inhibiting the mitochondrial mediated apoptosis pathway as reflected by inhibition of caspase-3 activity, normalization of Bcl-2/Bax levels and improved mitochondrial function. Moreover, GRS prevented cardiomyocytes mitochondrial fission and upregulated AMPKα phosphorylation. Interestingly, AMPK activation prevented hypoxia and reoxygenation induced mitochondrial fission in cardiomyocytes and GRS actions were significantly attenuated by knockdown of AMPKα. Collectively, these data show that GRS is effective in mitigating MI/R injury by suppressing mitochondrial mediated apoptosis and modulating AMPK activation-mediated mitochondrial fission, thereby providing a rationale for future clinical applications and potential therapeutic strategy for MI/R injury.

YiQiFuMai Powder Injection Protects against Ischemic Stroke via Inhibiting Neuronal Apoptosis and PKCδ/Drp1‐Mediated Excessive Mitochondrial Fission

“…Aberrant mitochondrial dynamics play critical roles in the pathological processes of ischemic stroke [ 14 ]. Previous studies have shown that YQFM protects against myocardial ischemia/reperfusion injury via AMPK pathway mediated mitochondrial fission [ 39 ] and oxygen-glucose deprivation-induced PC12 cell apoptosis through ER stress [ 36 ]. However, the effects of YQFM against mitochondrial dysfunction and excessive fission induced by ischemic stroke have not been fully elucidated.…”

“…YQFM also ameliorates blood-brain barrier (BBB) dysfunction through NF- κ B and ROCK1/MLC signaling pathways [ 37 , 38 ]. More importantly, YQFM is effective in mitigating myocardial ischemia/reperfusion injury by modulating AMPK activation-mediated mitochondrial fission [ 39 ]. However, the effects and potential mechanisms of YQFM on ischemic stroke-induced neuronal mitochondrial fission have not been fully elucidated.…”

Tnfrsf12a-Mediated Atherosclerosis Signaling and Inflammatory Response as a Common Protection Mechanism of Shuxuening Injection Against Both Myocardial and Cerebral Ischemia-Reperfusion Injuries

“…Cardiac left ventricular function and coronary blood flow were assessed non-invasively at 18 h after MIRI using an ultra-high resolution small animal ultrasound Vevo 2100 Imaging System (VisualSonics, Toronto, ON, Canada) equipped with a 30 MHz transducer ( Chen et al, 2016 ; Li et al, 2016 ). The mice were anesthetized using 1.5–2.0% isoflurane in O 2 gas.…”

<p>The Traditional Chinese Medicine Compound, GRS, Alleviates Blood–Brain Barrier Dysfunction</p>

“…17 Previous findings suggest that GRS mitigates myocardial I/R injury by suppressing mitochondria-mediated apoptosis and modulating AMP-activated protein kinase-mediated mitochondrial fission. 18 However, the effects of GRS on ischemic stroke are yet to be characterized.…”