数字农科院2.0

Cyanidin-3-O-Glucoside Mitigates Hepatotoxicity Induced by 2-Amino-3-Methylimidazo[4,5-f]Quinoline via Endogenous and Exogenous Apoptotic Signaling Pathways: Evidence From In Vivo and In Silico Studies

文献类型： 外文期刊

作者： Wang, Shaoxuan;Pan, Fei;Xu, Xinyan;Fan, Qian;Wang, Yangyang;Zhao, Lei;Zhao, Liang

作者机构：

关键词： 2-amino-3-methylimidazo[4,5-f]quinoline;apoptosis;cyanidin-3-O-glucoside;liver;molecular dynamics simulations

期刊名称： MOLECULAR NUTRITION & FOOD RESEARCH

ISSN： 1613-4125

年卷期： 2025 年 70 卷 1 期

页码：

收录情况： SCIE（2025版）

摘要： Heterocyclic aromatic amines (HAAs), potential carcinogens formed in processed meats, have been linked to liver injury. This study evaluated whether cyanidin-3-O-glucoside (C3G, 100 mg/kg) protects against liver injury by the representative HAA 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 20 mg/kg) in mice, and explored mechanisms by integrated approaches: biochemical assays, histology, Western blot, and molecular dynamics (MD) simulations. Results demonstrated that C3G significantly ameliorated IQ-induced liver injury, as indicated by reduced serum AST and ALT and inflammatory cytokines (IL-6, IL-1 beta, TNF-alpha) levels. Additionally, C3G restored redox homeostasis by inhibiting lipid peroxidation and protein carbonylation, while enhancing antioxidant defenses (GSH, GSH-Px, and SOD). Mechanistically, C3G exerted its protective effects via multiple anti-apoptotic pathways. Specifically, it attenuated mitochondrial apoptosis by lowering the Bax/Bcl-2 ratio and inhibiting cytochrome c-caspase-9/3 activation. It also alleviated endoplasmic reticulum (ER) stress by downregulating GRP78/ATF4/CHOP and caspase-12. Furthermore, C3G interfered with death receptor signaling by reducing Fas/FasL/FADD activation and caspase-8, while upregulating CFLAR. MD simulations further demonstrated that C3G binds to the hydrophobic pocket of BAX and weakens BAX-BIM interactions. These results conclusively identify C3G as a multi-target agent against IQ-induced liver damage, highlighting its promise for development into a novel dietary strategy to counteract the toxicological risks of processed meat consumption.

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