Abstract
8-gingerol (8-Gin) is the series of phenolic substance that is extracted from ginger. Although many studies have revealed that 8-Gin has multiple pharmacological properties, the possible underlying mechanisms of 8-Gin against myocardial fibrosis (MF) remains unclear. The study examined the exact role and potential mechanisms of 8-Gin against isoproterenol (ISO)-induced MF. Male mice were intraperitoneally injected with 8-Gin (10 and 20 mg/kg/d) and concurrently subcutaneously injected with ISO (10 mg/kg/d) for 2 weeks. Electrocardiography, pathological heart morphology, myocardial enzymes, reactive oxygen species (ROS) generation, degree of apoptosis, and autophagy pathway-related proteins were measured. Our study observed 8-Gin significantly reduced J-point elevation and heart rate. Besides, 8-Gin caused a marked decrease in cardiac weight index and left ventricle weight index, serum levels of creatine kinase and lactate dehydrogenase (CK and LDH, respectively), ROS generation, and attenuated ISO-induced pathological heart damage. Moreover, treatment with 8-Gin resulted in a marked decrease in the levels of collagen types I and III and TGF-β in the heart tissue. Our results showed 8-Gin exposure significantly suppressed ISO-induced autophagosome formation. 8-Gin also could lead to down-regulation of the activities of matrix metalloproteinases-9 (MMP-9), Caspase-9, and Bax protein, up-regulation of the activity of Bcl-2 protein, and alleviation of cardiomyocyte apoptosis. Furthermore, 8-Gin produced an obvious increase in the expressions of the PI3K/Akt/mTOR signaling pathway-related proteins. Our data showed that 8-Gin exerted cardioprotective effects on ISO-induced MF, which possibly occurred in connection with inhibition of ROS generation, apoptosis, and autophagy via modulation of the PI3K/Akt/mTOR signaling pathway.
Highlights
Myocardial fibrosis (MF) refers to excessive accumulation of collagen fibers and a significant increase in collagen concentration in the myocardium (Lu et al, 2018)
Oxygen deficiency occurrence leads to the excessive production of reactive oxygen species (ROS), causes up-regulation of the expression of Bax followed by release of cytochrome c, and cleaves Caspase-9 leading to activation of the mitochondrial apoptosis pathway, regulating the process of apoptosis (Gatica et al, 2015; Hu et al, 2015)
Effects of 8-Gingerol on Gross Examination and Cardiac Function In Figure 2A, macroscopic observations showed a significant increase in mice heart size and a deeper color after continuous injection of ISO for 14 days compared to the CON group
Summary
Myocardial fibrosis (MF) refers to excessive accumulation of collagen fibers and a significant increase in collagen concentration in the myocardium (Lu et al, 2018). Autophagy is a mechanism of cell self-protection, which is essential for maintaining the homeostasis of the intracellular environment (Li et al, 2018a). Many researchers have found that reactive oxygen species (ROS) form one of the main intracellular signal transducers in the autophagy process (Cabral-Pacheco et al, 2020). Excessive generation of ROS causes oxidative damage in the myocardium and leads to the hyperactivation of autophagy followed by cardiomyocyte apoptosis (Li et al, 2014). Oxygen deficiency occurrence leads to the excessive production of ROS, causes up-regulation of the expression of Bax followed by release of cytochrome c, and cleaves Caspase-9 leading to activation of the mitochondrial apoptosis pathway, regulating the process of apoptosis (Gatica et al, 2015; Hu et al, 2015)
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