Abstract
Cardiac remodelling refers to a series of changes in the size, shape, wall thickness and tissue structure of the ventricle because of myocardial injury or increased pressure load. Studies have shown that cardiac remodelling plays a significant role in the development of heart failure. Zingerone, a monomer component extracted from ginger, has been proven to possess various properties including antioxidant, anti‐inflammatory, anticancer and antidiabetic properties. As oxidative stress and inflammation contribute to acute and chronic myocardial injury, we explored the role of zingerone in cardiac remodelling. Mice were subjected to aortic banding (AB) or sham surgery and then received intragastric administration of zingerone or saline for 25 days. In vitro, neonatal rat cardiomyocytes (NRCMs) were treated with zingerone (50 and 250 μmol/L) when challenged with phenylephrine (PE). We observed that zingerone effectively suppressed cardiac hypertrophy, fibrosis, oxidative stress and inflammation. Mechanistically, Zingerone enhanced the nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2)/antioxidant response element (ARE) activation via increasing the phosphorylation of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production. Additionally, we used Nrf2‐knockout (KO) and eNOS‐KO mice and found that Nrf2 or eNOS deficiency counteracts these cardioprotective effects of zingerone in vivo. Together, we concluded that zingerone may be a potent treatment for cardiac remodelling that suppresses oxidative stress via the eNOS/Nrf2 pathway.
Highlights
Pathological cardiac remodelling is defined by the structural and func‐ tional changes in the left ventricle (LV) in response to internal or external cardiovascular damage or influence such as hypertension, myocardial ischaemia, metabolic‐related heart disease and valvular heart disease, and it is a precursor of clinical heart failure (HF).[1]
Because of the potent antioxidant and anti‐inflammatory proper‐ ties of zingerone, we further investigated the effect of zingerone on cardiac oxidative stress and inflammation, and we found that the CD45‐labelled leucocytes, CD68‐labelled macrophage infil‐ tration and 4‐hydroxynonenal (4‐HNE) production decreased and that the activity of superoxide dismutase (SOD) increased in the hearts of the zingerone‐ treated mice subjected to aortic banding (AB) (Figure 3A‐E)
We found decreased protein expression levels of nucleus‐ Nrf[2] (N‐nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2)), heme oxygenase‐1 (HO‐1) and SOD and increased protein expression levels of Kelch‐like ECH‐associated protein and NOX2/gp[91] phox after AB surgery in vivo and after PE challenge in vitro
Summary
Pathological cardiac remodelling is defined by the structural and func‐ tional changes in the left ventricle (LV) in response to internal or external cardiovascular damage or influence such as hypertension, myocardial ischaemia, metabolic‐related heart disease and valvular heart disease, and it is a precursor of clinical heart failure (HF).[1]. Zingerone is a nontoxic and inexpensive compound extracted from a common seasoning in Chinese food, dried ginger, with var‐ ied pharmacological activities including antioxidant, anti‐inflamma‐ tory, anticancer and antidiabetic activities.[7] Numerous studies have found that zingerone is a potent antioxidant It protects DNA against stannous chloride‐induced ROS oxidative damage,[8] prevents oxida‐ tive stress in intestine smooth muscles[9] and reduces mitochondrial injury and lipid peroxidation.[10] zingerone has higher antioxidant activity than ascorbic acid[8] and exerts a scavenging ef‐ fect against peroxynitrite formed from the reaction of superoxide and nitric oxide.[11] Recently, accumulating evidence has suggested that zingerone protects the heart from myocardial infarction in‐ jury via its antioxidant and free radical scavenging properties.[12,13,14] Another study revealed that pretreatment with zingerone relieves hyperlipidaemia and cardiac hypertrophy in isoproterenol‐induced myocardial infarcted rats.[15] it is not clear whether zing‐ erone exerts protective effects in AB‐induced cardiac remodelling. This investigation was designed to clarify the role of zing‐ erone in cardiac remodelling induced by AB surgery
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