Cardioprotective Effect of Taxifolin against Isoproterenol-Induced Cardiac Injury through Decreasing Oxidative Stress, Inflammation, and Cell Death, and Activating Nrf2/HO-1 in Mice

• Published in: Biomolecules (Basel, Switzerland) Vol. 12; no. 11; p. 1546
• Main Authors: Obeidat, Heba M, Althunibat, Osama Y, Alfwuaires, Manal A, Aladaileh, Saleem H, Algefare, Abdulmohsen I, Almuqati, Afaf F, Alasmari, Fawaz, Aldal’in, Hammad Khalifeh, Alanezi, Abdulkareem A, Alsuwayt, Bader, Abukhalil, Mohammad H
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 23.10.2022; MDPI
• Subjects: Acids; Animals; Antioxidants; Apoptosis; Bcl-2 protein; Bioflavonoids; Calcium-binding protein; Cardiac glycosides; Cardiotonic agents; Cardiotoxicity; Cardiovascular diseases; Care and treatment; Caspase-3; Cell death; Creatine; Creatine kinase; Enzymes; Flavones; Flavonoids; Glutathione; Health aspects; Heart; Heart diseases; IL-1β; Inflammation; Isoproterenol; Kinases; L-Lactate dehydrogenase; Lactic acid; myocardial injury; NF-κB protein; Nrf2; Oxidative stress; Pharmaceutical research; Physiology; Signal transduction; taxifolin; Transcription factors; Troponin; Troponin I; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Jordan; United States > US
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom12111546

Oxidative stress and inflammation are key components in cardiovascular diseases and heart dysfunction. Herein, we evaluated the protective effects of (+)-taxifolin (TAX), a potent flavonoid with significant antioxidant and anti-inflammatory actions, on myocardial oxidative tissue injury, inflammation, and cell death, using a mouse model of isoproterenol (ISO)-induced acute myocardial injury. Mice were given TAX (25 and 50 mg/kg, orally) for 14 days before receiving two subsequent injections of ISO (100 mg/kg, s.c.) at an interval of 24 h on the 15th and 16th days. The ISO-induced cardiac tissue injury was evidenced by increased serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH), along with several histopathological changes. The ISO also induced increased malondialdehyde (MDA) with concomitant declined myocardial glutathione level and antioxidant enzymes activities. Moreover, ISO-induced heart injury was accompained with elevated cardiac NF-κB p65, TNF-α, IL-1β, Bax, and caspase-3, as well as decreased Bcl-2, Nrf2, and HO-1. Remarkably, TAX reduced the severity of cardiac injury, oxidative stress, inflammation, and cell death, while enhancing antioxidants, Bcl-2, and Nrf2/HO-1 signaling in ISO-injected mice. In conclusion, TAX protects against ISO-induced acute myocardial injury via activating the Nrf2/HO-1 signaling pathway and attenuating the oxidative tissue injury and key regulators of inflammatory response and apoptosis. Thus, our findings imply that TAX may constitute a new cardioprotective therapy against acute MI, which undoubtedly deserves further exploration in upcoming human trials.