Crocetin reduces expression of receptor for advanced glycation end products (RAGE) on endothelial cells induced by AGE

Abstract

Abstract: AIM: To investigate the effects of crocetin on receptor for advanced glycation end products (RAGE) mRNA expression in bovine endothelial cells (BEC) induced by advanced glycation end products (AGE) and the possible mechanisms involved.METHODS: The BEC were preincubated with crocetin(1, 0.1 and 0.01 μmol/L) for 12 h, then exposed to AGE (100 mg/L).The RAGE mRNA expression was detected by RT-PCR analysis, the intercellular adhesion molecule-1 (ICAM-1) was measured by ELISA. The extracellular superoxide ion and thiobarbituric acid reactive substances (TBARS) were assessed with superoxide ion kit and colorimetric assay, respectively. The intracellular H₂O₂ was also detected using the probe 2, 7-dichlorofluorescein (DCFH).The mitochondrial membrane potential(MMP) and mitochodrial Succinate dehydrogenase(MSDH) were analyzed by the retention of rhodamine123 (Rh123) and MTT.RESULTS: Compared with AGE Group, crocetin was able to significantly reduce RAGE mRNA expression (P<0.05), decrease the content of super anion and TBARS in supernatant media (P<0.01 or P<0.05) and H₂O₂ in cells (P<0.05).Spontaneously, the MMP and the activity of MSDH were improved.Furthermore, the expression of ICAM-1 protein was suppressed by crocetin in a time-and dose-dependant manner.CONCLUSION: These results demonstrated that crocetin could inhibit RAGE over-expression in AGEexposed BEC by suppressing the generation of reactive oxygen species active oxygen(ROS).This study suggested that crocetin might have beneficial effects in the treatment of diabetic vascular complications.

Key words: crocetin, advanced glycation end products(AGE), receptor for AGE(RAGE), reactive oxygen species(ROS), endothelial cells, ICAM-1 protein

CLC Number:

R965

XIANG Min, QIAN Zhi-yu, ZHOU Cheng-hua. Crocetin reduces expression of receptor for advanced glycation end products (RAGE) on endothelial cells induced by AGE[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(6): 663-670.

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