Abstract
Myocardial ischemia is a high-risk disease among middle-aged and senior individuals. After thrombolytic therapy, heart tissue can potentially suffer further damage, which is called myocardial ischemia-reperfusion injury (MIRI). At present, the treatment methods and drugs for MIRI are scarce and cannot meet the current clinical needs. The mechanism of MIRI involves the interaction of multiple factors, and the current research hotspots mainly include oxidative stress, inflammation, calcium overload, energy metabolism disorders, pyroptosis, and ferroptosis. Traditional Chinese medicine (TCM) has multiple targets and few toxic side effects; clinical preparations containing Panax ginseng C. A. Mey., Panax notoginseng (Burk.) F. H. Chen, Aralia chinensis L., cardioprotection, and other Chinese herbal medicines have been used to treat patients with coronary heart disease, angina pectoris, and other cardiovascular diseases. Studies have shown that saponins are the main active substances in TCMs containing Panax ginseng C. A. Mey., Panax notoginseng (Burk.) F. H. Chen, Aralia chinensis L., and Radix astragali. In the present review, we sorted the saponin components with anti-MIRI effects and their regulatory mechanisms. Each saponin can play a cardioprotective role via multiple mechanisms, and the signaling pathways involved in different saponins are not the same. We found that more active saponins in Panax ginseng C. A. Mey. are mainly dammar-type structures and have a strong regulatory effect on energy metabolism. The highly active saponin components of Aralia chinensis L. are oleanolic acid structures, which have significant regulatory effects on calcium homeostasis. Therefore, saponins in Chinese herbal medicine provide a broad application prospect for the development of highly effective and low-toxicity anti-MIRI drugs.
Highlights
To date, revascularization, such as thrombolysis, is an effective method for the treatment of ischemic cardiomyopathy in patients with acute myocardial infarction (Yang et al, 2018)
Improving intracellular calcium handling via regulating sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) Recovering mitochondrial respiration, preventing mPTP opening, decreasing cytochrome C release and preventing apoptosis; regulating KATP channel Regulating PI3K/Akt/HO-1 signaling pathway Inhibiting CaSR/ERK1/2 and the related apoptotic signaling pathways; regulating energy metabolism Preventing cardiomyocyte apoptosis by reducing the release of LDH and CK Inhibiting oxidative stress and apoptosis by Nrf2/HO-1, p38 and JNK pathways Inhibiting the activation of NF-κb
Recent studies have revealed the important roles of pyroptosis and ferroptosis in the pathogenesis of myocardial ischemia-reperfusion injury (MIRI) (Wang Z. et al, 2018; Li W. et al, 2020)
Summary
Revascularization, such as thrombolysis, is an effective method for the treatment of ischemic cardiomyopathy in patients with acute myocardial infarction (Yang et al, 2018). Ginseng total saponins can enhance myocardial energy metabolism by regulating the tricarboxylic acid cycle pathway as well as reduce MIRI by inhibiting inflammation and oxidative damage (Wang et al, 2012). Panax notoginseng saponins were found to have a protective effect against rat MIRI and cardiomyocyte hypoxia-reoxygenation (HR) by regulating autophagy and apoptosis via the HIF-1α/BNIP3 and PI3K/Akt pathways (Chen et al, 2011) (Table 1) Ginsenosides, such as ginsenoside Rb1, ginsenoside Rg1, ginsenoside Rb3, ginsenoside Rg3, ginsenoside Rd, and ginsenoside Re, are mainly dammarane-type structures, with different types and positions of glycosides that result in unique physicochemical and biological activities (Aravinthan et al, 2015; Liu X.-W. et al, 2019) (Figure 2).
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