Preconditioning L6 Muscle Cells with Naringin Ameliorates Oxidative Stress and Increases Glucose Uptake

Abstract

Enhanced oxidative stress contributes to pathological changes in diabetes and its complications. Thus, strategies to reduce oxidative stress may alleviate these pathogenic processes. Herein, we have investigated Naringin mediated regulation of glutathione (GSH) & intracellular free radical levels and modulation of glucose uptake under oxidative stress in L6 cell lines. The results from the study demonstrated a marked decrease in glutathione with a subsequent increase in free radical levels, which was reversed by the pretreatment of Naringin. We also observed that the increased malondialdehyde level, the marker of lipid peroxidation on induction of oxidative stress was retrieved on Naringin pretreatment. Addition of Naringin (100 μM) showed approximately 40% reduction in protein glycation in vitro. Furthermore, we observed a twofold increase in uptake of fluorescent labeled glucose namely 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2 - NBDG) on Naringin treatment in differentiated L6 myoblast. The increased uptake of 2-NBDG by L6 myotubes may be attributed due to the enhanced translocation of GLUT4. Our results demonstrate that Naringin activate GSH synthesis through a novel antioxidant defense mechanism against excessive Reactive Oxygen Species (ROS) production, contributing to the prevention of oxidative damage in addition to its effect on glycemic control.

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

“…Second, we observed that NRG could exert remarkable antihyperglycemic effects (Table 1) in STZ-induced diabetic rats. Its mechanism has multiple components: (i) NRG activates glutathione (GSH) synthesis through a novel antioxidant defense mechanism against excessive ROS production, which contributes to the prevention of oxidative damage in addition to its effect on glycemic control (Dhanya et al 2015); (ii) NRG plays important roles in preventing the progression of hyperglycemia, partly by binding to starch by increasing hepatic glycolysis and the glycogen concentration and lowering hepatic gluconeogenesis (Shen et al 2012); (iii) NRG exhibits antidiabetic effects in a rat model of type 2 diabetes mellitus (T2DM) by potentiating the antioxidant defense system and suppressing pro-inflammatory cytokine production (Mahmoud et al 2012). Third, this study demonstrates the inhibitory effect of NRG on myocardial remodeling and cardiac fibrosis in STZinduced diabetic rats by inhibiting the NF-κB pathway.…”

Therapeutic potential of naringin: an overview

“…In L6 myoblast cells subjected to oxidative stress, pretreatment with naringin (3 or 24 h) reversed the decrease in glutathione (GSH) and increases in both intracellular free radicals and glucose uptake. Naringin (100 lM) also led to a reduction (40%) in protein glycation (Dhanya et al 2015). In the rat glomerular mesangial cell line HBZY-1, naringin (10 lM) obviously activated the Nrf2 signalling pathway and enhanced the expression and activity of its downstream target, HO-1 .…”

Comparative investigation of phytochemicals among ten citrus herbs by ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight mass spectrometry and evaluation of their antioxidant properties

“…Liu et al found hesperidin could block the ROS; improve the activities of SOD, CAT, and GSH; recover glutathione levels; and inhibit high glucose-induced cell apoptosis in RGC-5 cells [28]; hesperidin was also similarly effective in human RPE cells (ARPE-19) [29]. Dhanya et al reported that naringin could promote GSH synthesis by a new antioxidant defense mechanism, which inhibited plenty of ROS generation and improved oxidative damage and glycemic control in L6 Muscle Cells [30]. Lu et al also reported that naringin and nobiletin could prevent ROS formation, and increased SOD and GSH activity in H 2 O 2 -induced PC12 cells [31].…”