Zingerone attenuates aortic banding‐induced cardiac remodelling via activating the eNOS/Nrf2 pathway

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.

Activation of Nrf2 by Lithospermic Acid Ameliorates Myocardial Ischemia and Reperfusion Injury by Promoting Phosphorylation of AMP-Activated Protein Kinase α (AMPKα)

“…However, LA pretreatment increased eNOS but not iNOS or nNOS levels. Our previous study suggested that eNOS/Nrf2 pathway regulates pressure overload-induced cardiac remodeling (Liu et al, 2019). In addition, previous studies reported that the transcription activity of Nrf2 depends largely on the nuclear translocation of Nrf2 (Silva-Islas and Maldonado, 2018).…”

Thymoquinone ameliorates pressure overload‐induced cardiac hypertrophy by activating the AMPK signalling pathway

“…Excessive ROS accumulation has been associated with a progression to cardiac fibrosis and end‐stage heart failure 12,13,42,43 . Targeting oxidative stress has been the subject of investigation in the preclinical setting and demonstrated highly promising results 44‐46 . As a bioactive natural compound, TQ is one of the agents that has been considered as potent antioxidants and has been extensively studied in the past decade.…”

Anti‐inflammatory activity of ginger modulates macrophage activation against the inflammatory pathway of monosodium glutamate

“…Liu et al. (2019) found that intragastric administration of zingerone to mice for 28 days at a dose of 10 or 20 mg kg −1 day −1 decreased the infiltration of CD68 positive macrophages. Zingerone is known to have potent pharmacological activities including antioxidant and anti‐inflammatory properties.…”