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Original Research Article | OPEN ACCESS

Down-modulation of endoplasmic reticulum stress-initiated apoptosis by huperzine A in isoproterenol-provoked myocardial infarction rat model: Role of Nrf2/HO-1 signaling axis

Zhongkui Li1 , Wenbo Liu2, Lufang Gao1, Daokang Xiang4

1Department of Cardiac Surgery, Guizhou Provincial People's Hospital; 2Guizhou Blood Center, Guiyang, Guizhou 550002, China.

For correspondence:-  Zhongkui Li   Email: lizhongkui999@qq.com   Tel:+868515922979

Accepted: 16 July 2020        Published: 31 August 2020

Citation: Li Z, Liu W, Gao L, Xiang D. Down-modulation of endoplasmic reticulum stress-initiated apoptosis by huperzine A in isoproterenol-provoked myocardial infarction rat model: Role of Nrf2/HO-1 signaling axis. Trop J Pharm Res 2020; 19(8):1685-1691 doi: 10.4314/tjpr.v19i8.17

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the myocardial protective effect of huperzine A (HPA), a sesquiterpene alkaloid, in a rat model of isoproterenol (ISP)-provoked MI and ER stress.
Methods: Three groups of rats were used: control, ISP and ISP+HPA groups. The following indices were assayed using standard protocols: oxidative stress parameters, including NADPH oxidase 4 (NOX4), reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1); indices of calcium homeostasis, namely, sarcoplasmic and endoplasmic reticulum calcium ATPase isoform 2a (SERCA2a); ER stress parameters, viz, protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), glucose-regulated protein 78 (GRP78), and C/EBP homologous protein (CHOP); and indices of apoptosis, i.e.,  B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-12].
Results: Oxidative/ER stress and cardiomyocyte apoptosis were up-modulated (p < 0.05), while SERCA2a, a key calcium handling channel, was downmodulated in the ISP group (p < 0.05). In contrast, HPA treatment ameliorated these ISP-induced myocardial aberrations. (p < 0.05).
Conclusion: These results indicate that HPA might be a potential therapeutic candidate for MI and associated cardiac problems.

Keywords: Caspase-12, ER stress, Huperzine A, Myocardial infarction, SERCA2a

Impact Factor
Thompson Reuters (ISI): 0.523 (2021)
H-5 index (Google Scholar): 39 (2021)

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