Therapeutic Potential of Polyphenols in Cardiac Fibrosis

Abstract

Cardiac fibrosis, in response to injury and stress, is central to a broad constellation of cardiovascular diseases. Fibrosis decreases myocardial wall compliance due to extracellular matrix (ECM) accumulation, leading to impaired systolic and diastolic function and causing arrhythmogenesis. Although some conventional drugs, such as β-blockers and renin-angiotensin-aldosterone system (RAAS) inhibitors, have been shown to alleviate cardiac fibrosis in clinical trials, these traditional therapies do not tend to target all the fibrosis-associated mechanisms, and do not hamper the progression of cardiac fibrosis in patients with heart failure. Polyphenols are present in vegetables, fruits, and beverages and had been proposed as attenuators of cardiac fibrosis in different models of cardiovascular diseases. Together with results found in the literature, we can show that some polyphenols exert anti-fibrotic and myocardial protective effects by mediating inflammation, oxidative stress, and fibrotic molecular signals. This review considers an overview of the mechanisms of cardiac fibrosis, illustrates their involvement in different animal models of cardiac fibrosis treated with some polyphenols and projects the future direction and therapeutic potential of polyphenols on cardiac fibrosis.

Date Palm Pollen Extract Avert Doxorubicin-Induced Cardiomyopathy Fibrosis and Associated Oxidative/Nitrosative Stress, Inflammatory Cascade, and Apoptosis-Targeting Bax/Bcl-2 and Caspase-3 Signaling Pathways

“…DOX also interferes with iron regulation [ 24 ], up-regulates NF-κB expression, which consequently causes the release of pro-inflammatory cytokines, i.e., tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), and triggers vascular and cardiac inflammatory reaction [ 25 ] and exaggerates their downstream apoptotic pathways [ 26 ]. In addition, oxidative stress activates several pro-fibrogenic factors, which enhances the accumulation of extracellular matrix and development of cardiac fibrosis [ 27 ], remodeling [ 28 ], and eventual cardiac dysfunction [ 29 ]. DOX is still in use.…”

Effects of Isorhamnetin in Human Amniotic Epithelial Stem Cells in vitro and Its Cardioprotective Effects in vivo

“…Previously, we have reported that ISO, a flavonol, alleviates hepatic fibrosis in NASH model mice (Ganbold et al, 2019). Although several flavonols have been reported to improve cardiac dysfunction and fibrosis (Suzuki et al, 2007;Li et al, 2013;Geetha et al, 2014;Guo et al, 2015;Zhang et al, 2018), very little is known about the effect of ISO on cardiac hypertrophy and fibrosis. Microarray analysis of ISO-treated hAESCs revealed that ISO has strong antifibrotic effects as well as anti-inflammatory and antioxidative functions.…”

Hydrogen Sulfide as a Potential Alternative for the Treatment of Myocardial Fibrosis

“…The activation of the β-adrenergic nervous system and RAAS has been commonly found in fibrotic HF patients, and β-blockers and RAAS inhibitors have been suggested as a first-line treatment to correct the underlying cardiac dysfunction and reduce morbidity [7,118]. The overstimulation of β-adrenoceptor may result in the impairment of the negative modulation of H 2 S on the β-adrenoceptor system, resulting in a calcium overload, leading to the impairment of cardiac contractility and, ultimately, to cardiomyocyte death [119].…”