Attenuation of ROS-mediated myocardial ischemia–reperfusion injury by morin via regulation of RISK/SAPK pathways
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Oxidative stress plays an important role in the pathogenesis of myocardial ischemia–reperfusion (IR) injury. Morin, a bioflavonoid, has demonstrated antioxidant, anti-inflammatory and other diverse pharmacological activities in various experimental models such as isoproterenol-induced myocardial injury, doxorubicin-induced cardiotoxicity and neurotoxicity, as well as cisplatin-induced nephrotoxicity. Thus, this study aimed to evaluate the effect of morin in myocardial IR injury model and its underlying mechanisms.
To accomplish this, male albino Wistar rats were pre-treated with morin (40 and 80 mg/kg; po) for 28 days and on 29th day, rats experienced 45-min myocardial ischemia followed by 60-min reperfusion.
In comparison to IR-control group, morin pre-treatment significantly normalized hemodynamic parameters, restored antioxidant status, improved pathological changes, reduced the release of cardiac injury markers, inhibited inflammation (TNF-α/IL-6/NFκB/IKKβ) and apoptosis (increased Bcl-2, decreased Bax/Caspase-3 and TUNEL positivity) in the myocardium. This improvement in antioxidant, inflammation and anti-apoptosis markers could be due to downregulation of SAPK (p38/JNK) pathway and upregulation of survival kinase, i.e. RISK pathway (ERK/eNOS) in the myocardium.
Thus, morin attenuated myocardial IR injury in rats by regulation of RISK/SAPK pathways.
KeywordsIschemia–reperfusion Morin MAPK Akt/eNOS
Protein kinase A
Endothelial nitric oxide synthase
- ERK 1/2
Extracellular regulated kinase 1/2
c-Jun N-terminal kinase
Left anterior descending coronary artery
Left ventricular end diastolic pressure
Mean arterial pressure
Mitogen-activated protein kinase
Nuclear factor-kappa B
Reperfusion-induced salvage kinase
Stress-activated protein kinase
Tumour necrosis factor-α
All authors are grateful to the technical staff for their support. First author is obliged to DST-SERB, India (PDF/2016/003885) for providing fellowship and financial assistance to conduct the study.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 10.Yang X, Yue R, Zhang J, Zhang X, Liu Y, Chen C, et al. Gastrin protects against myocardial ischemia/reperfusion injury via activation of RISK (reperfusion injury salvage kinase) and SAFE (survivor activating factor enhancement) pathways. J Am Heart Assoc. 2018;7:e005171.PubMedPubMedCentralGoogle Scholar
- 33.Lv X, Xu T, Wu Q, Zhou Y, Huang G, Xu Y, et al. 6-Gingerol activates PI3K/Akt and inhibits apoptosis to attenuate myocardial ischemia/reperfusion injury. Evid Based Complement Altern Med. 2018;2018:9024034.Google Scholar
- 36.Xu T, Qin G, Jiang W, Zhao Y, Xu Y, Lv X. 6-Gingerol protects heart by suppressing myocardial ischemia/reperfusion induced inflammation via the PI3K/Akt-dependent mechanism in rats. Evid Based Complement Altern Med. 2018;2018:6209679.Google Scholar
- 38.Kim M, Lorinsky MK, Gold CA, Lahey SJ, Fusco DS, Rosinski DJ, et al. Usefulness of circulating caspase-3 p17 and caspase-1 p20 peptides and cardiac troponin 1 during cardioplegia to gauge myocardial preservation. Am J Cardiol. 2018;9149:32209–14.Google Scholar