Galanthamine improves myocardial ischemia-reperfusion-induced cardiac dysfunction, endoplasmic reticulum stress-related apoptosis, and myocardial fibrosis by suppressing AMPK/Nrf2 pathway in rats

Xiaolin Hou; Minhuan Fu; Biao Cheng; Yu Kang; Dili Xie

doi:10.21037/atm.2019.10.108

Galanthamine improves myocardial ischemia-reperfusion-induced cardiac dysfunction, endoplasmic reticulum stress-related apoptosis, and myocardial fibrosis by suppressing AMPK/Nrf2 pathway in rats

Ann Transl Med. 2019 Nov;7(22):634. doi: 10.21037/atm.2019.10.108.

Authors

Xiaolin Hou¹, Minhuan Fu², Biao Cheng², Yu Kang³, Dili Xie²

Affiliations

¹ Department of Cardiology, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu 610072, China.
² Department of Geriatric Cardiology, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu 610072, China.
³ Department of Cardiology, West China Medical College, Sichuan University, Chengdu 610065, China.

Abstract

Background: Myocardial ischemia/reperfusion (I/R) injury is an important cause of myocardial infarction and heart failure after cardiovascular surgery. Galanthamine (Gal) is an important Amaryllidaceae alkaloid with anti-acetylcholinesterase and anti-inflammatory activity. The purpose of this study was to investigate the role of Gal in myocardial I/R injury.

Methods: In this study, an animal model of myocardial I/R injury was constructed, and the rats were divided into five groups (n=10): the sham, I/R model, I/R + Gal (1 mg/kg), I/R + Gal (3 mg/kg), and I/R + Aspirin (20 mg/kg) groups. The expression of related proteins was detected by Western blotting and Immunohistochemistry, and Histological lesion was detected by HE staining.

Results: Results showed that Gal improves I/R-induced cardiac dysfunction in rats. Moreover, Gal inhibits I/R-induced endoplasmic reticulum stress (ERS)-related apoptosis by suppressing the expression of CHOP, Cleaved caspase 12, and caspase 3, and promoting the expression of CADD34 and BiP in rats. Furthermore, Gal mitigates I/R-induced myocardial fibrosis through restraining the expression of α-SMA and Collagen I in rats. Mechanically, Gal promoted the expression of AMPKα1, Nrf2 and HO-1. However, AMPK inhibitor Compound C exhibited the opposite effects. Collectively, this finding suggests that Gal improves I/R-induced cardiac dysfunction, ERS-related apoptosis, and myocardial fibrosis by activating AMPK/Nrf2 pathway in myocardial I/R rats.

Conclusions: Given this evidence, Gal may be a potential therapeutic drug for the treatment of I/R injury.

Keywords: Myocardial ischemia/reperfusion injury; adenosine-activated protein kinase; galanthamine, endoplasmic reticulum stress; nuclear factor erythroid-2-related factor 2.