Effect of gypenosides on RAGE expression and oxidative stress in human mesangial cells induced by AGEs / 中草药

ABSTRACT

Objective: To observe the effect of gypenosides (GP) on the expression of receptor for advanced glycated endproducts (RAGE) and the oxidative stress status of human mesangial cells (HMCs) induced by AGEs. Methods: HMCs were cultured in DMEM of low glucose containing 13% fetal bovine serum in vitro, which were divided into six groups normal control group (DMEM of low glucose containing 13% fetal bovine serum), AGEs group (AGEs 200mg/L), GP low-dose group (25 mg/L and AGEs 200 mg/L), GP mid-dose group (75 mg/L and AGEs 200 mg/L), GP high dose group (150 mg/L and AGEs 200 mg/L), and aminoguanidine positive control group (0.1 mmol/L and AGEs 200 mg/L). The expression of RAGE mRNA levels of each group was detected using semi-quantitative RT-PCR method, protein expression levels by Western blotting after cultured 72 h. Simultaneously, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in cell supernatant, and intracellular glutathione trace (GSH) in cell were measured. Results: AGEs could significantly promote the expression of RAGE and mRNA in HMCs (P<0.01), and enhance cellular oxidative stress levels. GP could effectively inhibit the expression of RAGE and mRNA, increase the level of SOD in cell supernatant and GSH in cell, reduce the level of MDA in cell supernatant in a dose-dependent manner compared with the control group, the difference was significant (P<0.05). Conclusion: AGEs stimulation can induce the high expression of RAGE in HMCs and enhance the level of oxidative stress in vitro. GP can down the high expression of RAGE stimulated by AGEs, while improve the oxidative stress in cells, and its possible mechanism of GP may block AGEs-RAGE-oxidative stress signaling pathways mediated by RAGE, it shows the lower levels of MDA and SOD and higher levels of GSH in cell.