Poncirin ameliorates cardiac ischemia-reperfusion injury by activating PI3K/AKT/PGC-1α signaling.

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.