Cardioprotective Effect of Taxifolin against Isoproterenol-Induced Cardiac Injury through Decreasing Oxidative Stress, Inflammation, and Cell Death, and Activating Nrf2/HO-1 in Mice
Heba M. Obeidat,
Osama Y. Althunibat,
Manal A. Alfwuaires,
Saleem H. Aladaileh,
Abdulmohsen I. Algefare,
Afaf F. Almuqati,
Fawaz Alasmari,
Hammad Khalifeh Aldal’in,
Abdulkareem A. Alanezi,
Bader Alsuwayt,
Mohammad H. Abukhalil
Affiliations
Heba M. Obeidat
Department of Medical Analysis, Princess Aisha Bint Al-Hussein College of Nursing and Health Sciences, Al-Hussein Bin Talal University, Ma’an 71111, Jordan
Osama Y. Althunibat
Department of Medical Analysis, Princess Aisha Bint Al-Hussein College of Nursing and Health Sciences, Al-Hussein Bin Talal University, Ma’an 71111, Jordan
Manal A. Alfwuaires
Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia
Saleem H. Aladaileh
Department of Medical Analysis, Princess Aisha Bint Al-Hussein College of Nursing and Health Sciences, Al-Hussein Bin Talal University, Ma’an 71111, Jordan
Abdulmohsen I. Algefare
Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia
Afaf F. Almuqati
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hafr Al-Batin, Hafr Al-Batin 31991, Saudi Arabia
Fawaz Alasmari
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Hammad Khalifeh Aldal’in
Department of Medical Support, Al-Karak University College, Al-Balqa Applied University, Al-Karak 19117, Jordan
Abdulkareem A. Alanezi
Department of Pharmaceutics, College of Pharmacy, University of Hafr Al-Batin, Hafr Al-Batin 31991, Saudi Arabia
Bader Alsuwayt
Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al-Batin, Hafr Al-Batin 31991, Saudi Arabia
Mohammad H. Abukhalil
Department of Medical Analysis, Princess Aisha Bint Al-Hussein College of Nursing and Health Sciences, Al-Hussein Bin Talal University, Ma’an 71111, Jordan
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.
