Loganin protects against myocardial ischemia-reperfusion injury by modulating oxidative stress and cellular apoptosis via activation of JAK2/STAT3 signaling

  • Int J Cardiol. 2023 Oct 9:131426. doi: 10.1016/j.ijcard.2023.131426.
Boyu Xia  1 ,  Jiaqi Ding  1 ,  Qi Li  1 ,  Koulong Zheng  2 ,  Jingjing Wu  3 ,  Chao Huang  4 ,  Kun Liu  1 ,  Qingsheng You  5 ,  Xiaomei Yuan  6
Affiliations
  • 1. Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
  • 2. Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
  • 3. Department of Cardiology, Suzhou Kowloon Hospital of Shanghai Jiaotong University School of Medicine, Suzhou, Jiangsu, China.
  • 4. Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
  • 5. Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. Electronic address: [email protected].
  • 6. Department of Cardiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. Electronic address: [email protected].
PMID: 37813285 DOI: 10.1016/j.ijcard.2023.131426
Abstract

Background: Myocardial ischemia-reperfusion injury (MIRI) is a pathological process that follows immediate revascularization of myocardial infarction and is characterized by exacerbation of cardiac injury. Loganin, a monoterpene iridoid glycoside derived from Cornus officinalis Sieb. Et Zucc, can exert cardioprotective effects in cardiac hypertrophy and atherosclerosis. However, its role in ischemic heart disease remains largely unknown.

Methods: Considering that Janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) has a protective effect on the heart, we developed a mouse model of MIRI to investigate the potential role of this pathway in loganin-induced cardioprotection.

Results: Our results showed that treatment with loganin (20 mg/kg) prevented the enlargement of myocardial infarction, myocyte destruction, serum markers of cardiac injury, and deterioration of cardiac function induced by MIRI. Myocardium subjected to I/R treatment exhibited higher levels of oxidative stress, as indicated by an increase in malondialdehyde (MDA) and dihydroethidium (DHE) density and a decrease in total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD), whereas treatment with loganin showed significant attenuation of I/R-induced oxidative stress. Loganin treatment also increased the expression of anti-apoptotic Bcl-2 and reduced the expression of Caspase-3/9, Bax, and the number of TUNEL-positive cells in ischemic cardiac tissue. Moreover, treatment with loganin triggered JAK2/STAT3 phosphorylation, and AG490, a JAK2/STAT3 Inhibitor, partially abrogated the cardioprotective effects of loganin, indicating the essential role of JAK2/STAT3 signaling in the cardioprotective effects of loganin.

Conclusions: Our data demonstrate that loganin protects the heart from I/R injury by inhibiting I/R-induced oxidative stress and cellular Apoptosis via activation of JAK2/STAT3 signaling.

Keywords
Apoptosis; Ischemia reperfusion injury; JAK2; Loganin; Oxidative stress; STAT3.
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