Protective Effect of Natural Medicinal Plants on Cardiomyocyte Injury in Heart Failure: Targeting the Dysregulation of Mitochondrial Homeostasis and Mitophagy

Figure 2

Myocardial injury and mitochondrial homeostasis disorder in heart failure. Mitochondria play an important role in energy production, oxidative stress, maintaining constant intracellular Ca²⁺ concentration, and preserving cellular structural integrity. Moreover, their dysfunction is related to the mechanisms of myocardial injury. Mitophagy can remove damaged mitochondria over time and thus, avoid the ROS-mediated oxidative stress damage and production of certain toxic effects on cells, and effectively maintain homeostasis of the internal cardiomyocyte environment. Cardiomyocyte mitophagy is substantially decreased during the pathological course of heart failure. Impaired mitophagy accelerates the progression of heart failure after myocardial infarction. Damaged mitochondrial DNA induces the mitochondrial fission mechanism, inhibits mitochondrial fusion, and leads to myocardial intracellular calcium overload, inflammatory injury, necrosis, apoptosis, and myocardial fibrosis; it promotes heart failure. The mitochondrial damage mechanism caused by various factors may be one of the pathological mechanisms behind heart failure. The effect of the SOD-led antioxidant defense system is reduced, free radical metabolism is distorted, and oxidative stress levels are enhanced. Mitochondria are the metabolic centers of cellular supply and the preferred targets for cytotoxicity and hypoxia-ischemia damage. Therefore, free radical attack on the mitochondrial membrane may lead to dysregulated mitophagy and excessive mitochondrial fission. This ultimately leads to a “vicious cycle” of enhanced mitochondrial oxidative stress and dysregulation of cellular homeostasis. ROS-mediated oxidative stress is closely associated with mitochondrial damage.