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Poncirin ameliorates cardiac ischemia-reperfusion injury by activating PI3K/AKT/PGC-1α signaling.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2022 Feb 15; Vol. 917, pp. 174759. Date of Electronic Publication: 2022 Jan 12. - Publication Year :
- 2022
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Abstract
- Poncirin, a flavonoid glycoside derivative extracted from the fruits of Poncirus trifoliata (trifoliate orange or Chinese bitter orange), has a variety of documented bioactivities, including anti-tumor, anti-inflammatory, and antioxidant effects. Oxidative stress is a major underlying factor in the pathogenesis of cardiac ischemia-reperfusion (I/R) injury. Therefore, we investigated the protective efficacy of poncirin on primary cardiomyocytes subjected to anoxia-reoxygenation (A/R) injury in vitro, and on rat hearts subjected to ischemia-reperfusion (I/R) injury in vivo. Poncirin pretreatment enhanced cardiomyocyte survival, inhibited A/R-induced oxidative stress by upregulating cellular antioxidant capacity, suppressed mitochondrial depolarization, and ultimately inhibited apoptosis. Similarly, systemic poncirin treatment significantly reduced cardiomyocyte apoptosis and infarct size in rat hearts. In addition, activity of the PI3K/AKT/PGC-1α pathway was significantly increased by poncirin pretreatment in both A/R and I/R injury models, while PI3K and PGC-1α inhibitors abolished all poncirin related effects, suggesting that this pathway is essential for the cardioprotective effects of poncirin. Pretreatment with the PGC-1α inhibitor reversed effects of poncirin without affecting p-AKT expression, indicating that PGC-1α is downstream of AKT. In conclusion, both in vitro and in vivo studies suggested that poncirin alleviates cardiac ischemia-reperfusion injury by mitigating oxidative stress, which is dependent on activation of the PI3K/AKT/PGC-1α signaling pathway.<br /> (Copyright © 2022. Published by Elsevier B.V.)
- Subjects :
- Animals
Male
Rats
Cardiotonic Agents pharmacology
Cardiotonic Agents therapeutic use
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Rats, Sprague-Dawley
Apoptosis drug effects
Flavonoids pharmacology
Flavonoids therapeutic use
Myocardial Reperfusion Injury drug therapy
Myocardial Reperfusion Injury metabolism
Myocardial Reperfusion Injury pathology
Myocytes, Cardiac drug effects
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
Oxidative Stress drug effects
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 917
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 35032487
- Full Text :
- https://doi.org/10.1016/j.ejphar.2022.174759