Paeonol Protects Against Myocardial Ischemia/Reperfusion-Induced Injury by Mediating Apoptosis and Autophagy Crosstalk

Abstract

Many studies have shown that crosstalk exists between apoptosis and autophagy, despite differences in mechanisms between these processes. Paeonol, a major phenolic compound isolated from Moutan Cortex Radicis, the root bark of Paeonia × suffruticosa Andrews (Paeoniaceae), is widely used in traditional Chinese medicine as an antipyretic, analgesic and anti-inflammatory agent. In this study, we investigated the detailed molecular mechanisms of the crosstalk between apoptosis and autophagy underlying the cardioprotective effects of paeonol in rats subjected to myocardial ischemia/reperfusion (I/R) injury. Myocardial I/R injury was induced by occlusion of the left anterior descending coronary artery (LAD) for 1 h followed by 3 h of reperfusion. Paeonol was intravenously administered 15 min before LAD ligation. We found that paeonol significantly improved cardiac function after myocardial I/R injury and significantly decreased myocardial I/R-induced arrhythmia and mortality. Paeonol also significantly decreased myocardial infarction and plasma LDH activity and Troponin-I levels in carotid blood after I/R. Compared with vehicle treatment, paeonol significantly upregulated Bcl-2 protein expression and significantly downregulated the cleaved forms of caspase-8, caspase-9, caspase-3 and PARP protein expression in the I/R injured myocardium. Myocardial I/R-induced autophagy, including the increase of Beclin-1, p62, LC3-I, and LC3-II protein expression in the myocardium was significantly reversed by paeonol treatment. Paeonol also significantly increased the Bcl-2/Bax and Bcl-2/Beclin-1 ratios in the myocardium after I/R injury. The cardioprotective role of paeonol during I/R injury may be due to its mediation of crosstalk between apoptotic and autophagic signaling pathways, which inhibits apoptosis and autophagic cell death.

Mitochondrial Quality Control in Cardiac-Conditioning Strategies against Ischemia-Reperfusion Injury

“…Additionally, the mitochondrial anti-apoptotic protein BCL-2 regulates the autophagic process by interacting with BECLIN-1 at the OMM. Protection against I/R damage by the phenolic compound Paenol is related not only carried out with its antioxidant and anti-inflammatory properties, but with increased expression of BCL-2 and downregulation of BECLIN-1, BAX, LC3, and p62, sustaining the hypothesis of crosstalk between apoptosis and autophagy [246]. Additionally, it has been shown that vitamin D, MitoTEMPO or Mdivi-1 treatments reduced COX4 colocalization with LC3 (autophagosomes) in cardiomyocytes subjected to H/R [179].…”

Paeonol for the Treatment of Atherosclerotic Cardiovascular Disease: A Pharmacological and Mechanistic Overview

“…The result showed that paeonol significantly improved cardiac function after I/R. Compared with vehicle treatment, paeonol significantly downregulated the cleaved forms of caspase-8, caspase-9, caspase-3 protein expression, and myocardial I/R-induced autophagy was significantly reversed by paeonol treatment ( 116 ). Similar research showed that paeonol could induce VSMCs autophagy by activating the class III PI3K/Beclin-1 signaling pathway, thus ultimately inhibiting VSMCs apoptosis ( 117 ).…”

Paeonol Attenuates Quorum-Sensing Regulated Virulence and Biofilm Formation in Pseudomonas aeruginosa

“…Paeonol is one of the main compounds present in traditional Chinese medicine, including Moutan cortex, Cynanchum paniculatum , and Paeonia lactiflora Pal. Paeonol is known to exert multiple pharmacological effects, immunomodulation, and liver and kidney protection, antitumor, antipyretic, analgesic, anti-inflammatory, and antibacterial and has been widely used as a nutrient supplement ( Zhang et al, 2019 ; Tsai et al, 2020 ).…”