Protocatechuic acid reverses myocardial infarction mediated by β‐adrenergic agonist via regulation of Nrf2/HO‐1 pathway, inflammatory, apoptotic, and fibrotic events

Abstract

Myocardial infarction (MI) is an instant ischemic death of cardiomyocytes that remains a major global cause of mortalities. MI is accompanied by oxidative, inflammatory, apoptotic, and fibrotic insults. Protocatechuic acid (PCA) is a polyphenolic compound with various potent biological activities. In this study, we explored the possible cardioprotective role of PCA against isoproterenol (ISO)-mediated MI. Rats were either injected with ISO (85 mg/kg, subcutaneously) or pretreated with PCA (100 or 200 mg/kg, orally). PCA supplementation markedly normalized ISO-induced disturbed cardiac function markers (creatine kinase-MB, lactate dehydrogenase, and troponin T). Notably, PCA administration exerted remarkable increases in glutathione and its derived enzymes, superoxide dismutase, and catalase, as well as decreases in malondialdehyde and nitric oxide levels in the injured cardiac tissue. The molecular findings validated the augmented cellular antioxidative capacity by PCA via increasing the gene expressions of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1. The cardioprotective efficacy of PCA extended to suppress cardiac inflammation as demonstrated by the decreased levels of tumor necrosis factor-alpha, interleukin-1 beta, and nuclear factor kappa B. Additionally, PCA prevented cardiomyocyte loss and fibrosis by decreasing Bax, caspase-3, transforming growth factor-β1 and matrix metalloproteinase-9, and enhancing B-cell

Inflammatory Forms of Cardiomyocyte Cell Death in the Rat Model of Isoprenaline-Induced Takotsubo Syndrome

“…The pathological increase in the concentration of circulating catecholamines and their excessive release from the cardiac sympathetic nerve endings lead to direct damage to the cardiomyocytes [30]. The pathophysiological mechanisms involved in catecholamineinduced myocardial injury include increased oxygen demand of the cardiomyocytes with insufficient supply, oxidative stress, calcium overload, myofibril over-contraction, and upregulation of the expression and release of inflammatory cytokines [31][32][33][34][35][36][37][38][39][40][41][42]. Indeed, histopathological examinations of the myocardium of rats treated with supraphysiological doses of catecholamines showed focal necrosis and degeneration of the cardiomyocytes, disordered myofibrils, advanced cytoplasmic vacuolization, myocardial infiltration with inflammatory cells, and tissue fibrosis [43][44][45].…”

Cocoa Shell Extract Reduces Blood Pressure in Aged Hypertensive Rats via the Cardiovascular Upregulation of Endothelial Nitric Oxide Synthase and Nuclear Factor (Erythroid-Derived 2)-like 2 Protein Expression

“…Several of the bioactive components from CSE, namely, protocatechuic acid, gallic acid, and flavan-3-ols, can participate in the observed increase. Protocatechuic acid and other hydroxybenzoic acids activate the Nrf2 signaling pathway [ 44 ], and in a rat model of myocardial infarction treatment with protocatechuic-acid-stimulated Nrf2, it increases GSH and several antioxidant enzymes [ 45 ]. Gallic acid, another component of CSE, has also been shown to increase Nrf2, with beneficial effects on cardiac hypertrophy [ 46 ].…”

Microbiota-Derived Natural Products Targeting Cancer Stem Cells: Inside the Gut Pharma Factory

“…The health-promoting potential of plant extracts and plant-derived secondary metabolites is widely recognised [186][187][188]. Numerous beneficial effects of polyphenols on human health, such as antioxidant [189][190][191][192][193], anti-inflammatory [194][195][196], immunomodulatory [197][198][199], cardioprotective [200][201][202], neuroprotective [203][204][205], anti-carcinogenic [206][207][208], and prebiotic properties [209], have been reported. Thanks to the plethora of chemical structures they exhibit, natural anticancer compounds may act as cytotoxic agents [210][211][212], anti-mitotic agents [213], angiogenesis inhibitors [214,215], topoisomerase inhibitors [216], apoptosis inducers [217] and cancer invasion [218], migration [219] and proliferation inhibitors [220][221][222].…”