Mitochondrial Damage in Myocardial Ischemia/Reperfusion Injury and Application of Natural Plant Products

Abstract

Ischemic heart disease (IHD) is currently one of the leading causes of death among cardiovascular diseases worldwide. In addition, blood reflow and reperfusion paradoxically also lead to further death of cardiomyocytes and increase the infarct size. Multiple evidences indicated that mitochondrial function and structural disorders were the basic driving force of IHD. We summed up the latest evidence of the basic associations and underlying mechanisms of mitochondrial damage in the event of ischemia/reperfusion (I/R) injury. This review then reviewed natural plant products (NPPs) which have been demonstrated to mitochondria-targeted therapeutic effects during I/R injury and the potential pathways involved. We realized that NPPs mainly maintained the integrality of mitochondria membrane and ameliorated dysfunction, such as improving abnormal mitochondrial calcium handling and inhibiting oxidative stress, so as to protect cardiomyocytes during I/R injury. This information will improve our knowledge of mitochondrial biology and I/R-induced injury’s pathogenesis and exhibit that NPPs hold promise for translation into potential therapies that target mitochondria.

Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation‑induced cardiomyocyte injury based on network pharmacology and in vitro validation

“…Mitochondria are intricately involved in the complex pathological mechanisms of H/R injury. Significant factors include excessive ROS production, dysfunction in the electron transport chain, dysregulation of calcium homeostasis, abnormal opening of the mitochondrial permeability transition pore (mPTP), depolarization of MtMP and inappropriate activation of apoptosis ( 28 ). During myocardial hypoxia, there is a gradual impairment of mitochondrial electron transport system function and compromised mitochondrial energy metabolism ( 29 ).…”

Recent Advances in Natural Plant-based Treatment of Myocardial Ischemia-reperfusion Injury

“…The anti-apoptotic proteins Bcl-2 reside in the mitochondrial outer membrane and inhibit the release of Cyt c, while the pro-apoptotic Bcl-2 proteins, Bax, can reside in the cytoplasm and translocate to the mitochondria after signal transduction, where it promotes release of Cyt c [100]. In addition, the loss of MMP and the burst of ROS will also cause the loss of Cyt c from mitochondria into the cytoplasm, triggering apoptosis [101].…”

“…These factors cause damage to the myocardial intima, myocardial contractile dysfunction, and cardiomyocyte death [7]. Clinical treatment of MIRI is mainly focused on inhibiting the inflammatory response, reducing oxidative stress, preventing Ca 2+ overload, and restoring energy metabolism [8][9][10].…”

“…At present, a number of natural medicines have been found to exhibit therapeutic effects on MIRI, Review including glycosides, flavonoids, alkaloids, phenols, carbohydrates, terpenes, organic acids, amino acids and catechins. These natural substances play a vital role in decreasing MIRI by inhibiting oxidative stress and apoptosis, reducing mitochondrial damage, and improving energy metabolism [9]. This article summarizes the latest papers on the treatment of MIRI with NPPs, and discusses the intervention effect of NPPs on MIRI through inhibition of Ca 2+ overload, oxidative stress injury, mitochondrial damage, inflammatory response and other related mechanisms.…”