Naringin protects against anoxia/reoxygenation-induced apoptosis in H9c2 cells via the Nrf2 signaling pathway

Abstract

Naringin (Nar) is a major and active flavanone glycoside derivative of several citrus species. The antioxidant properties of Nar have an important function in its cardioprotective effects in various models. However, the effects of Nar on Nrf2 activation and the expression of its downstream genes in myocardial cells are yet to be elucidated. This study was designed to investigate the protective effects of Nar against anoxia/reoxygenation (A/R)-induced injury in H9c2 cells and determine its effects on the activity of Nrf2 and the expression of phase II antioxidant enzymes. H9c2 cells were pretreated with Nar for 6 h before exposure to A/R. A/R treatment severely injured the H9c2 cells, which was accompanied by apoptosis. Nar also suppressed the A/R-induced mitochondrial membrane depolarization and caspase-3 activation. Nar pretreatment significantly reduced the apoptotic rate by enhancing the endogenous anti-oxidative activity of superoxide dismutase, glutathione peroxidase, and catalase, thereby inhibiting intracellular reactive oxygen species generation. Moreover, the presence of Nar alone in H9c2 cells increased the nuclear translocation of Nrf2 in a dose- and time-dependent manner, as well as consistently increased the protein levels of heme oxygenase (HO-1) and glutamate cysteine ligase (GCLC). Nar increased the phosphorylation of ERK1/2, PKCδ, and AKT. However, the Nar-mediated Nrf2 activation and cardioprotection were abolished through the genetic silencing of Nrf2 by siRNA and partially inhibited by specific inhibitors of ERK1/2, PKCδ, and AKT. Therefore, Nar provided cardioprotection by inducing the phosphorylation of ERK1/2, PKCδ, and AKT, which subsequently activated Nrf2 and its downstream genes.

Naringin abates adverse effects of cadmium‐mediated hepatotoxicity: An experimental study using HepG2 cells

“…Also, NIN gets converted to naringenin, which has been shown to impart health‐promoting properties like including anti‐inflammatory and antioxidant activities . A number of reports advocate the ability of NIN to exert its antioxidant and cytoprotective property via activating Nrf2, which aids in the activation of various antioxidants such as GSH, Glutathione S‐transferase (GST) and downstream molecules that help in ameliorating against oxidative stress . Hence, we put forward that plant‐derived polyphenolic compounds will help in reducing the adverse effects of cadmium‐mediated hepatotoxicity.…”

Potential Protective Effects of Bioactive Constituents from Chinese Propolis against Acute Oxidative Stress Induced by Hydrogen Peroxide in Cardiac H9c2 Cells

“…MDA is recognized as an indirect oxidative stress marker of cellular injury due to itself is one of the end products of lipid peroxidation [29]. SOD and GSH-Px are known as main endogenous antioxidant enzymes which can neutralize free radicals and protect cells from ROS insults [30]. In our hands, we found that H9c2 cells exposed to H 2 O 2 showed a significant increase in MDA levels (Figure 4(a)), which was ameliorated by pretreatment with 5 and 10  μ M caffeate derivatives (BZC, CAPE, and CNC).…”

Naringin Decreases TNF-α and HMGB1 Release from LPS-Stimulated Macrophages and Improves Survival in a CLP-Induced Sepsis Mice

“…Its therapeutic potential has been reported d for various diseases including atherosclerosis, cardiovascular disorders, and cancers [ 15 ]. Previous studies have shown that naringin protects against LPS-induced endotoxin shock in mice and RAW264.7 macrophages [ 16 , 18 , 24 ], and upregulates HO-1 expression via phosphatidylinositol 3-kinase/Akt, ERK1/2, protein kinase C-α, and NF-E2-related factor-2 in H9C2 myoblast cells [ 25 ]. However, the precise mechanism underlying naringin’s anti-septic action in macrophages remained unclear.…”