Salvianolic acid B inhibits myocardial I/R-induced ROS generation and cell apoptosis by regulating the TRIM8/GPX1 pathway

Abstract

Context Salvianolic acid B (SalB) can attenuate myocardial ischemia/reperfusion (I/R) injury, but the mechanisms are not entirely known. Objective Our study investigates if SalB protects cardiomyocytes against I/R injury by regulating Tripartite motif (TRIM) protein. Materials and methods AC16 cardiomyocytes were treated with I/R, and then with SalB (10, 25 and 50 μM) for 24 h, while control cells were cultured under normal conditions. Female Sprague-Dawley rats were subjected to I/R injury, and then intravenously injected with 20, 40, or 60 mg/kg SalB or saline, as a control, rats received sham operation and saline injection. Results Upon treatment, apoptotic rate, reactive oxygen species (ROS), and malondialdehyde (MDA) were increased 10-, 3.8-, and 1.3-fold, respectively, while superoxide dismutase (SOD) activity was reduced by 62.1% compared to control cells. I/R treatment elevated the mRNA and protein expression of TRIM8. SalB treatment remarkably abolished the above-mentioned effects of I/R treatment. TRIM8 knock-down could partially alleviate I/R-induced myocardial injury. TRIM8 overexpression promoted cardiomyocyte injury, which was alleviated by SalB. Moreover, TRIM8 negatively regulated protein expression of antioxidant enzyme glutathione peroxidase 1 (GPX1). TRIM8 protein interacted with GPX1 and TRIM8 overexpression promoted GPX1 ubiquitnation. GPX1 knock-down abolished the protective effects of SalB on I/R-injured cardiomyocytes. Our in vivo experiments confirmed the effects of SalB on I/R-induced myocardial injury. Discussion and conclusions SalB protected cardiomyocytes from I/R-induced apoptosis and oxidative stress in vitro and in vivo , which was partly mediated by the TRIM8/GPX1 axis. This suggests that down-regulation of TRIM8 expression may ameliorate I/R-induced myocardial injury.

Investigating the mechanism of action of Danhong injection and its components against myocardial ischemia-reperfusion injury

“…Further, we explored the different pharmacodynamic effects of DHI, PM, and SM on MI/RI. Studies have widely reported the anti-inflammatory and antioxidant effects of the secondary metabolite fractions that were primarily composed of phenolic acids, including salvianolic acid B [34][35] , lithospermic acid [36] , rosmarinic acid [37] , salvianolic acid A [38] , and protocatechuic aldehyde [39] . However, the effects and material basis of the primary metabolites with low polarity, mainly consisting of sugars and amino acids, have not been studied in depth.…”

Salvianolic acids and its potential for cardio-protection against myocardial ischemic reperfusion injury in diabetes

“…SAB has been shown to effectively attenuate cardiovascular injuries by reducing the expression of related inflammatory factors, inhibiting apoptosis, and reducing oxidative stress in experimental settings (117). Numerous studies have demonstrated the cardiomyocyte protective effects of SAB during myocardial ischemia-reperfusion injury (MIRI) and its ability to reduce oxidative stress-induced damage (118). Similar to SAA, SAB also reduces post-ischemic LDH leakage (119).…”

Research progress of glutathione peroxidase family (GPX) in redoxidation

“…For example, in the study of traumatic brain injury in mice, the lack of GPX1 increased the attack of ROS on hippocampal neurons, causing damage to post-traumatic memory function (Kim et al, 2022). In studies of myocardial ischemia-reperfusion injury, GPX1 KO exacerbated oxidative stress injury during myocardial ischemia-reperfusion (Lu et al, 2022). In addition, in the study of oxidative stress injury in cochlear spiral ganglion neuronal cells (SGNs), it was found that when GPX1 is knocked out, the oxidative stress damage of SGNs by peroxynitrite is aggravated, resulting in loss of SGNs and loss of hearing (Wang et al, 2022).…”