Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Daucosterol pretreatment ameliorates myocardial ischemia reperfusion injury via ROS-mediated NLRP3 inflammasome activation

Guixiang Zhao¹, Xiaoyun Ma², Juledezi Hailati², Zhen Bao², Maerjiaen Bakeyi², Zhiqiang Liu²

¹Department of Cardiology, The Sixth Affiliated Hospital of Xinjiang Medical University; ²Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830054, China.

For correspondence:- Zhiqiang Liu Email: ZhiqiangLiudjk@163.com Tel:+869914366851

Accepted: 29 April 2020 Published: 31 May 2020

Citation: Zhao G, Ma X, Hailati J, Bao Z, Bakeyi M, Liu Z. Daucosterol pretreatment ameliorates myocardial ischemia reperfusion injury via ROS-mediated NLRP3 inflammasome activation. Trop J Pharm Res 2020; 19(5):1031-1036 doi: 10.4314/tjpr.v19i5.18

© 2020 The authors.
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Abstract

Purpose: To determine the involvement of NLRP3 signaling pathway in the preventive role of daucosterol in acute myocardial infarction (AMI).

Methods: H9C2 cells were pretreated with daucosterol before hypoxia/reoxygenation (HR) injury. Myocardial ischemia reperfusion (IR) was established in male SD rats, followed by reperfusion. Myocardial infarct size was measured. The serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were determined using commercial kits. NLRP3 inflammasome activation was assessed by western blotting.

Results: Myocardial infarct size was smaller after IR injury in rats pretreated with daucosterol (10 and 50 mg/kg) than that pretreated with daucosterol (0 and 1 mg/kg). The increase in LDH, CK, and MDA levels after IR injury was reduced following daucosterol pretreatment. Reactive oxygen species (ROS) production increased, whereas T-SOD activity decreased after IR injury. These changes were prevented by pretreatment of daucosterol (10 and 50 mg/kg). Protein expression of NLRP3 inflammasome increased after IR injury in H9C2 cells while pretreatment with daucosterol inhibited the upregulation of NLRP3 inflammasome.

Conclusion: The cardioprotective effect of daucosterol pretreatment appears to be mediated via the inactivation of ROS-related NLRP3 inflammasome, suggesting that daucosteol might be a potential therapeutic drug for AMI.

Keywords: Daucosterol, Myocardial ischemia, Reperfusion injury, Reactive oxygen species, NLRP3 inflammasome