Visnagin prevents isoproterenol-induced myocardial injury by attenuating oxidative stress and inflammation and upregulating Nrf2 signaling in rats

被引:32
作者
Abukhalil, Mohammad H. [1 ,2 ]
Hussein, Omnia E. [3 ]
Aladaileh, Saleem H. [2 ,4 ]
Althunibat, Osama Y. [2 ]
Al-Amarat, Wesam [5 ]
Saghir, Sultan A. [2 ]
Alfwuaires, Manal A. [6 ]
Algefare, Abdulmohsen, I [6 ]
Alanazi, Khalid M. [7 ]
Al-Swailmi, Farhan K. [4 ]
Kamel, Emadeldin M. [8 ]
Mahmoud, Ayman M. [3 ,9 ]
机构
[1] Al Hussein Bin Talal Univ, Fac Sci, Dept Biol, Maan 71111, Jordan
[2] Al Hussein Bin Talal Univ, Princess Aisha Bint Al Hussein Fac Nursing & Hlth, Dept Med Anal, Maan, Jordan
[3] Beni Suef Univ, Fac Sci, Zool Dept, Physiol Div, Salah Salim St, Bani Suwayf 62514, Egypt
[4] Univ Hafr Al Batin, Coll Pharm, Dept Pharm Practice, Hafar al Batin, Saudi Arabia
[5] Al Balqa Appl Univ, Al Karak Univ Coll, Dept Med Support, As, Jordan
[6] King Faisal Univ, Fac Sci, Dept Biol Sci, Al Hasa, Saudi Arabia
[7] King Saud Univ, Coll Sci, Zool Dept, Riyadh, Saudi Arabia
[8] Beni Suef Univ, Fac Sci, Chem Dept, Bani Suwayf, Egypt
[9] Beni Suef Univ, Res Inst Med & Aromat Plants, Biotechnol Dept, Bani Suwayf, Egypt
关键词
isoproterenol; myocardial infarction; Nrf2; oxidative stress; visnagin; ACTIVATED RECEPTOR-GAMMA; PROTECTIVE ROLE; CELL-DEATH; INFARCTION; HEART; FAILURE; AGONIST; MARKERS; GENE; BETA;
D O I
10.1002/jbt.22906
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Oxidative tissue injury and inflammatory responses play major roles in cardiovascular diseases and heart failure. Visnagin (VIS) is a natural bioactive component of Ammi visnaga, with promising radical scavenging and anti-inflammatory activities. This study explored the protective effect of VIS against isoproterenol (ISO)-induced acute myocardial injury and oxidative stress in rats. VIS was supplemented for 14 days, and the rats received ISO (100 mg/kg) twice at an interval of 24 h. ISO-induced myocardial injury was characterized by elevated serum CK-MB, LDH, and troponin-I associated with increased heart weight and several histopathological changes. ISO increased reactive oxygen species (ROS), malondialdehyde (MDA), NF-kappa B p65, TNF-alpha, IL-6, and decreased glutathione and antioxidant enzymes in rats' hearts. VIS prevented myocardial injury and ameliorated the cardiac function markers, ROS, MDA, NF-kappa B p65, and pro-inflammatory cytokines in ISO-intoxicated rats. In addition, VIS decreased Bax mRNA and caspases, and upregulated Nrf2, HO-1, Bcl-2, and PPAR gamma. Molecular docking simulations revealed the binding method of VIS to NF-kappa B, Keap1, and PPAR gamma. In conclusion, VIS protects against ISO-induced acute myocardial injury by attenuating oxidative tissue injury and reducing key inflammatory and apoptosis markers. In vivo and in silico results showed that activation of Nrf2/HO-1 signaling and PPAR gamma mediates the cardioprotective effect of VIS.
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页数:13
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