Si-Miao-Yong-An Decoction Maintains the Cardiac Function and Protects Cardiomyocytes from Myocardial Ischemia and Reperfusion Injury

Abstract

Objective. The aim of this study was to determine whether Si-Miao-Yong-An decoction (SMYAD) could protect cardiomyocytes from ischemia/reperfusion (I/R) injury and its underlying mechanisms. Methods. C57BL/6 mice were used to establish a model of myocardial infarction by I/R injury and treated by SMYAD for 4 weeks. Then, the cardiac functions of mice were evaluated by cardiac magnetic resonance (CMR). Histopathological analysis for the heart remodeling was detected by H&E and Masson staining. The protein expression of collagen I, MMP9, and TNFα was detected by western blot in the heart tissues. H9C2 cells were used to establish the hypoxia/reoxygenation (H/R) model and SMYAD intervention. MTT assays detected the cell viability of myocardial cells. The expression level of IL-1β was evaluated by ELISA. The expression levels of LC3B-II/LC3B-I, p-mTOR, mTOR, NLRP3, procaspase 1, and cleaved-caspase 1 in H9C2 cells were evaluated by Western blot. Results. SMYAD improved cardiac functions such as ventricular volume and ejection fraction of the rats with ischemia/reperfusion injury. Morphological assay indicated that SMYAD reduced the scar size and inhibited fibrosis formation. It was found that SMYAD could regulate collagen I, MMP9, and TNFα protein expression levels in the heart tissues. SMYAD improved the survival rate of H9C2 cardiomyocytes in the H/R injury model. SMYAD elevated the rate of LC3B-II/LC3B-I protein expression, decreased the rate of p-mTOR/mTOR protein expression, and reduced expressions of caspase 1, NLRP3, and IL-1β in H/R cardiomyocytes. Conclusion. SMYAD exerted protective effects on ischemia/reperfusion injury in myocardial cells by activating autophagy and inhibiting pyroptosis. This might be the reason why SMYAD protected myocardial tissue and improved cardiac function in mice with ischemia/reperfusion.

HJ11 decoction restrains development of myocardial ischemia-reperfusion injury in rats by suppressing ACSL4-mediated ferroptosis

“…Thus, HJ11 decoction might intensify the metabolic rate of rats with myocardial I/R injury, which further resulted in a higher ROS level than that in rats of the Sham group. Mitochondrial damage is the main morphological characteristic feature of ferroptosis, such as shrinkage of the mitochondria and broken mitochondrial cristae (Cui et al, 2021). The mitochondrion is a major organelle involved in ATP production to provide the necessary cellular energy.…”

The crosstalk among autophagy, apoptosis, and pyroptosis in cardiovascular disease

“…In addition, a study showed that Simiaoyong An Decoction (SMYAD) had a protective effect on myocardial ischemia/reperfusion injury by activating autophagy and inhibiting pyroptosis, and improving the cardiac function of cardiomyocytes. The mechanism is that SMYAD increases the protein expression rate of LC3B-II/LC3B-I in H/R cardiomyocytes, reduces the protein expression rate of p-mTOR/mTOR, and downregulates the expression of Caspase-1, NLRP3, and IL-1β ( 105 ).…”

The Role of Pyroptosis and Autophagy in Ischemia Reperfusion Injury

“…In vitro experiments showed that SMYAD protected H9C2 cardiomyoblast cells from hyperoxia/reoxygenation (H/R). The in-depth experiment revealed that SMYAD upregulated the expression rate of LC3B-II/LC3B-I, reduced the expression rate of p-mTOR/mTOR, and downregulated the expression of NLRP3, caspase 1, and IL-1β in H/R cardiomyocytes, indicating that SMYAD activated autophagy and inhibited pyroptosis [ 83 ]. Our previous studies have shown that autophagy can be activated through the AMPK/mTOR pathway [ 84 ].…”