Carnosic acid protects against pressure overload‑induced cardiac remodelling by inhibiting the AKT/GSK3β/NOX4 signalling pathway

Abstract

Oxidative stress and apoptosis serve an important role in the development of pressure overload-induced cardiac remodelling. Carnosic acid (CA) has been found to exert antioxidant and anti-apoptotic effects. The present study investigated the underlying mechanism of CA protection and whether this effect was exerted against pressure overload-induced cardiac remodelling. Aortic banding (AB) surgery was performed to induce cardiac remodelling. Mice were randomly divided into four groups (n=15/group): i) Sham + vehicle; ii) sham + CA; iii) AB + vehicle; and iv) AB + CA. After 2 days of AB, 50 mg kg CA was administered orally for 12 days. Echocardiography, histological analysis and molecular biochemistry techniques were performed to evaluate the roles of CA. CA treatment decreased cardiac hypertrophy, fibrosis, oxidative stress and apoptosis in mice challenged with pressure overload. CA also decreased the cross-sectional area of cardiomyocytes and the mRNA and protein expression levels of hypertrophic markers. Furthermore, CA treatment decreased collagen deposition, α-smooth muscle actin expression and the mRNA and protein expression of various fibrotic markers. Additionally, CA reversed the AB-mediated increase in NAPDH oxidase (NOX) 2, NOX4 and 4-hydroxynonenal levels. The number of apoptotic cells was decreased following CA treatment following under conditions of pressure overload. CA also suppressed the activation of AKT and glycogen synthase kinase 3 β (GSK3β) in mice challenged with AB. The present results suggested that CA could inhibit pressure overload-induced cardiac hypertrophy and fibrosis by suppressing the AKT/GSK3β/NOX4 signalling pathway. Therefore, CA may be a promising therapy for cardiac remodelling.

Protective Effects of Carnosic Acid on Lipopolysaccharide-Induced Acute Kidney Injury in Mice

“…NOX4 plays a major role in ROS production in LPS-induced AKI [29,30]. Although the detailed molecular mechanism is not yet fully understood, several studies have shown the inhibitory action of carnosic acid on NOX4 expression [17,48,49]. In addition, upregulation of antioxidant enzymes by carnosic acid was observed in cisplatininduced nephrotoxicity [14].…”

“…Many studies have shown that the compound induces apoptosis in cancer cells [54] However, some studies have revealed the anti-apoptotic effect of carnosic acid on normal cells in inflammatory conditions [55][56][57][58][59]. In animal models of several inflammatory diseases, carnosic acid inhibited apoptosis to ameliorate inflammation and tissue injury [48,59,60]. Thus, the cytoprotective effect of carnosic acid may contribute to its therapeutic action on LPS-induced AKI.…”

Role of Terpenophenolics in Modulating Inflammation and Apoptosis in Cardiovascular Diseases: A Review

“…A study by Wei et al [ 47 ] demonstrated that carnosic acid exerted its cardioprotective effect by alleviating the progression of cardiac hypertrophy in overload pressure-induced myocardial hypertrophy in rats. Carnosic acid reduced the rise of protein and gene expression of hypertrophic markers, i.e., ANP, BNP and β-MHC.…”

Carnosic acid protects against doxorubicin-induced cardiotoxicity through enhancing the Nrf2/HO-1 pathway

“…14 As well, CA has been reported to protect against pressure overload-induced cardiac remodeling by inhibiting the AKT/GSK3β/NOX4 signaling pathway. 15 Thus, the present study aimed to determine whether carnosic acid has a therapeutic effect on cardiotoxicity induced by DOX.…”