Attenuation of ROS-mediated myocardial ischemia–reperfusion injury by morin via regulation of RISK/SAPK pathways

  • Vipin Kumar Verma
  • Salma Malik
  • Ekta Mutneja
  • Anil Kumar Sahu
  • Jagriti Bhatia
  • Dharamvir Singh AryaEmail author



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.

Graphic abstract


Ischemia–reperfusion Morin MAPK Akt/eNOS 



Protein kinase A


Creatinine kinase-MB




Endothelial nitric oxide synthase

ERK 1/2

Extracellular regulated kinase 1/2


Reduced glutathione


Heart rate






c-Jun N-terminal kinase


Left anterior descending coronary artery


Lactate dehydrogenase


Left ventricular end diastolic pressure


Mean arterial pressure


Mitogen-activated protein kinase




Myocardial infarction


Nuclear factor-kappa B


Phosphotidylinositol 3-kinase


Reperfusion-induced salvage kinase


Stress-activated protein kinase


Superoxide dismutase


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.


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Copyright information

© Maj Institute of Pharmacology Polish Academy of Sciences 2020

Authors and Affiliations

  1. 1.Cardiovascular Research Laboratory, Department of PharmacologyAll India Institute of Medical SciencesNew DelhiIndia

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