An in Silico Approach Reveals the Potential Function of Cyanidin-3-o-glucoside of Red Rice in Inhibiting the Advanced Glycation End Products (AGES)-Receptor (RAGE) Signaling Pathway.

Abstract

Introduction:Advanced glycation end products (AGEs) contribute to the pathogenesis of chronic inflammation, diabetes, micro and macrovascular complications, and neurodegenerative diseases through the binding with RAGE. Natural compounds can act as an alternative in disease therapy related to the AGEs-RAGE interactions. Cyanidin-3-O-glucoside is one of the potential anthocyanins found in red rice. Cyanidin-3-O-glucoside in red rice may interfere with the AGEs-RAGE signaling so that the potential mechanism of their interaction needs to be elucidated.Aim:This study aimed to investigate the potency of cyanidin-3-O-glucoside in red rice as an inhibitor of AGE-RAGE signaling pathway through in silico analysis.Methods:Our study used the 3D structures of AGEs and Cyanidin-3-O-glucoside compounds from PubChem and Receptor for AGEs (RAGE) from the RCSB Protein Data Bank (PDB) database. The molecular interactions of those compounds and RAGE were established using Hex 8.0 software, then visualized using Discovery Studio 2016 software.Results:Argypirimidine, pentosidine, pyrralline, and imidazole bound to the ligand-binding domain of RAGE with the binding energy of -247 kcal/mol, -350.4 kcal/mol, -591.1 kcal/mol, and -100.4 kcal/mol, respectively. The presence of cyanidin-3-O-glucoside in the imidazole-RAGE-cyanidin-3-O-glucoside complex could inhibit the interaction of imidazole-RAGE with a binding energy of -299 kcal/mol, which was lower than of imidazole-RAGE complex. The establishment of AGEs-Cyanidin-3-O-glucoside-RAGE complex showed that cyanidin-3-O-glucoside, which bound first to Argypirimidine and Pyrralline, could bound to RAGE at the same residue as those two AGEs did with the binding energy of -411.8 kcal/mol and -1305 kcal/mol, respectively. Based on the binding site location and energy, cyanidin-3-O-glucoside might have a biological function as an inhibitor of AGEs-RAGE interactions, which was more likely through the establishment of AGEs-cyanidin-3-O-glucoside-RAGE.Conclusion:This study suggests that cyanidin-3-O-glucoside in red rice can be a potential AGEs-RAGE inhibitor, leading to the regulation of the pro-inflammatory and oxidative damage in the cellular pathway.