Thymoquinone Attenuates Myocardial Ischemia/Reperfusion Injury Through Activation of SIRT1 Signaling

Abstract

Background/Aims: Myocardial ischemia/reperfusion (MI/R) injury is a leading factor responsible for damage in myocardial infarction, resulting in additional injury to cardiac tissues involved in oxidative stress, inflammation, and apoptosis. Thymoquinone (TQ), the main constituent of Nigella sativa L. seeds, has been reported to possess various biological activities. However, few reports regarding myocardial protection are available at present. Therefore, this study was conducted aiming to investigate the protective effect of TQ against MI/R injury and to clarify its potential mechanism. Methods: MI/R injury models of isolated rat hearts and neonatal rat cardiomyocytes were established. The Langendorff isolated perfused heart system, triphenyltetrazolium chloride staining, gene transfection, TransLaser scanning confocal microscopy, and western blotting were employed to evaluate the cardioprotection effect of TQ against MI/R injury. Results: Compared with the MI/R group, TQ treatment could remarkably improve left ventricular function, decrease myocardial infarct size and production of lactate dehydrogenase (LDH), and attenuate mitochondrial oxidative damage by elevating superoxide dismutase (SOD) activity and reducing production of hydrogen peroxide (H₂O₂) and malonaldehyde (MDA). Moreover, the cardioprotective effect of TQ was accompanied by up-regulated expression of SIRT1 and inhibition of p53 acetylation. Additionally, TQ treatment could also enhance mitochondrial function and reduce the number of apoptotic cardiomyocytes. Nonetheless, the cardioprotective effect of TQ could be mitigated by SIRT1 inhibitor sirtinol and SIRT1 siRNA, respectively, which was achieved through inhibition of the SIRT1 signaling pathway. Conclusions: The findings in this study demonstrate that TQ is efficient in attenuating MI/R injury through activation of the SIRT1 signaling pathway, which can thus reduce mitochondrial oxidative stress damage and cardiomyocyte apoptosis.

USP22 Protects Against Myocardial Ischemia–Reperfusion Injury via the SIRT1-p53/SLC7A11–Dependent Inhibition of Ferroptosis–Induced Cardiomyocyte Death

“…During subsequent experimentation, we further uncovered that SIRT1 inhibited ferroptosis-induced myocardial cell death through the p53/SLC7A11 axis. This is noteworthy as one previous study revealed that TQ confers protection against MI/R injury through activation of the SIRT1 signaling pathway to reduce mitochondrial oxidative stress damage and cardiomyocyte apoptosis by inhibiting p53 acetylation (Lu et al, 2018). Furthermore, another study also proposed that p53 (especially acetylation-defective mutant p53) positively regulates ferroptosis FIGURE 6 | Mechanism.…”

Thymoquinone reduces ischemia and reperfusion-induced intestinal injury in rats, through anti-oxidative and anti-inflammatory effects

“…One mechanism of TQ may be that it enhances the expression of endothelial nitric oxide synthase and increases nitric oxide levels, potent antioxidant which reacts with toxic molecular radicals, along with down-regulated nitric oxide synthase expression (25). TQ may have improved effects on endoplasmic stress and mitochondrial dysfunction and anti-apoptotic effects through activation of autophagy in damaged cells following numerous I/R models (13,(26)(27)(28)(29).…”

Autophagy and cardiac diseases: Therapeutic potential of natural products

“…PI3K/Akt/mTOR pathway was found to be activated by the aforementioned natural products, except for thymoquinone and polydatin, which needs further investigation. Another study 196 suggested that thymoquinone mitigated myocardial I/R injury by promoting the activation of SIRT1 and AMPK in this process, although autophagy was not directly explored. As for Danshen extracts, salvianolic acid B 169 and salvianic acid A (danshensu), 170 autophagy initiation was inhibited while autophagic flux was increased by salvianic acid A, as evidence by reduced p62 level and increased formation of autolysosomes.…”