Naringin inhibits high glucose-induced cardiomyocyte apoptosis by attenuating mitochondrial dysfunction and modulating the activation of the p38 signaling pathway

Abstract

Recently, naringin (NAR; 4',5,7-trihydroxyflavanone-7-rhamnoglucoside) has been shown to have cardioprotective properties. However, the specific mechanisms underlying its cardioprotective effects remain unclear. In this study, we aimed to investigate the cardioprotective effects of NAR and the possible underlying molecular mechanisms in cardiomyocytes using high glucose (HG) to induce apoptosis in H9c2 cells. The effect of NAR on apoptosis was assessed by Annexin V and propidium iodide staining, and by determining the levels of active caspase-3, -8 and -9. The effect of NAR on mitochondrial dysfunction was assessed by the loss of mitochondrial membrane potential (MMP). Our results demonstrated that exposure to HG induced apoptosis and mitochondrial dysfunction in cardiomyocytes. Treatment with NAR significantly increased MMP and inhibited the activation of caspase-3, -8 and -9. NAR attenuated the HG-induced p38 and p53 phosphorylation, decreased mitochondrial Bax and Bak expression, prevented the release of cytochrome c and increased Bcl-2 expression. Pre-treatment with SB203580, a p38 inhibitor, also suppressed p53 phosphorylation and prevented the loss of MMP, as well as apoptosis in the HG-treated H9c2 cells. Taken together, these data demonstrate that NAR inhibits HG-induced apoptosis by attenuating mitochondrial dysfunction and modulating the activation of the p38 signaling pathway.

Naringin protects cardiomyocytes against hyperglycemia-induced injuries in vitro and in vivo

“…First, consistent with the previously reported results (Huang et al 2013), we found that NRG markedly suppressed HG-triggered cytotoxicity and apoptosis, and it was suggested that NRG contributed to cardioprotection by attenuating mitochondrial dysfunction and inhibiting the activation of the p38 MAPK pathway. Our results are supported by a series of previous studies (Jagetia et al 2003, Kanno et al 2003.…”

“…NRG is recognized by more and more people due to its comprehensive physiological and pharmacological effects, including antioxidant (Jung et al 2003, Jeon et al 2004, Rajadurai & Prince 2007, Bodas et al 2011, Jain & Parmar 2011, Mahmoud et al 2012, antihypercholesterolemic (Jung et al 2003, Kim et al 2004, Jung et al 2006, anti-inflammatory (Jung et al 2003, Bodas et al 2011, Mahmoud et al 2012, cardioprotection (Huang et al 2013, Chen et al 2014a and anti-apoptotic effects (Jagetia et al 2003, Kanno et al 2003. Furthermore, Huang et al (2013) and Chen et al (2014a,b) demonstrated that NRG inhibited the MAPK pathway (p38 MAPK, ERK1/2 and JNK) in HG-induced injuries in H9c2 cardiac cells.…”

“…Furthermore, Huang et al (2013) and Chen et al (2014a,b) demonstrated that NRG inhibited the MAPK pathway (p38 MAPK, ERK1/2 and JNK) in HG-induced injuries in H9c2 cardiac cells. In recent years, many studies have shown that NRG could regulate glycolipid metabolism.…”

Protection of SAL B with H9C2 cells

“…Salvianolic acid B (Sal B, Figure 1), the most abundant water-soluble compound extracted from Danshen, has been found to exhibit potent antioxidative capability (Ho and Hong 2011) and protect cardiomyocytes (Xu et al 2011). Recently, Huang et al (2013) suggested that Sal B could inhibit symptoms of DM in rats, and these effects may partially be correlated with its antioxidant activity. However, there is little report about the mechanism of Sal B on high glucose-induced myocardial cell injury.…”

Stability-indicating densitometric high-performance thin-layer chromatographic method for the quantitative analysis of biomarker naringin in the leaves and stems ofRumex vesicariusL.

“…Naringin ( Figure 1) is widely found in grape and citrus fruits [6] and extensively used in functional foods [7]. It is reported to be an effective agent to treat breast cancer [8], progression of hyperglycemia [7], and cardiac diseases [9]. Naringin was determined in human plasma, rat plasma, food products, and different herbal formulations by liquid chromatography-mass spectrometry (LC-MS) [10], ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS) [11], LC-MS/MS [12], and ultra high-performance liquid chromatography (UHPLC) [13].…”