数字农科院2.0

A Novel Glycosylated Ferulic Acid Conjugate: Synthesis, Antioxidative Neuroprotection Activities In Vitro, and Alleviation of Cerebral Ischemia-Reperfusion Injury (CIRI) In Vivo

文献类型： 外文期刊

作者： Chen, Jian;Yuan, Yongjun;Tong, Litao;Yu, Manyou;Zhu, Yongqing;Liu, Qingqing;Deng, Junling;Wang, Fengzhang;Xiang, Zhuoya;Xia, Chen

作者机构：

关键词： ferulic acid;glycosylation conjugate;antioxidant;neuroprotection;CIRI

期刊名称： ANTIOXIDANTS

ISSN：

年卷期： 2025 年 14 卷 8 期

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收录情况： SCIE（2025版）

摘要： Antioxidative neuroprotection is effective at preventing ischemic stroke (IS). Ferulic acid (FA) offers benefits in the treatment of many diseases, mostly due to its antioxidant activities. In this study, a glycosylated ferulic acid conjugate (FA-Glu), with 1,2,3-triazole as a linker and bioisostere between glucose at the C6 position and FA at the C4 position, was designed and synthesized. The hydrophilicity and chemical stability of FA-Glu were tested. FA-Glu's protection against DNA oxidative cleavage was tested using pBR322 plasmid DNA under the Fenton reaction. The cytotoxicity of FA-Glu was examined via the PC12 cell and bEnd.3 cell tests. Antioxidative neuroprotection was evaluated, in vitro, via a H2O2-induced PC12 cell test, measuring cell viability and ROS levels. Antioxidative alleviation of cerebral ischemia-reperfusion injury (CIRI), in vivo, was evaluated using a rat middle cerebral artery occlusion (MCAO) model. The results indicated that FA-Glu was water-soluble (LogP -1.16 +/- 0.01) and chemically stable. FA-Glu prevented pBR322 plasmid DNA cleavage induced via center dot OH radicals (SC% 88.00%). It was a non-toxic agent based on PC12 cell and bEnd.3 cell tests results. FA-Glu significantly protected against H2O2-induced oxidative damage in the PC12 cell (cell viability 88.12%, 100 mu M) and inhibited excessive cell ROS generation (45.67% at 100 mu M). FA-Glu significantly reduced the infarcted brain areas measured using TTC stain observation, quantification (FA-Glu 21.79%, FA 28.49%, I/R model 43.42%), and H&E stain histological observation. It sharply reduced the MDA level (3.26 nmol/mg protein) and significantly increased the GSH level (139.6 nmol/mg protein) and SOD level (265.19 U/mg protein). With superior performance to FA, FA-Glu is a safe agent with effective antioxidative DNA and neuronal protective actions and an ability to alleviate CIRI, which should help in the prevention of IS.

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