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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\u2019s 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\u2013reperfusion 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 \u22121.16 \u00b1 0.01) and chemically stable. FA-Glu prevented pBR322 plasmid DNA cleavage induced via \u2022OH 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 \u03bcM) and inhibited excessive cell ROS generation (45.67% at 100 \u03bcM). 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&amp;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.<\/jats:p>","DOI":"10.3390\/antiox14080953","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:58:26Z","timestamp":1754564306000},"page":"953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Novel Glycosylated Ferulic Acid Conjugate: Synthesis, Antioxidative Neuroprotection Activities In Vitro, and Alleviation of Cerebral Ischemia\u2013Reperfusion Injury (CIRI) In Vivo"],"prefix":"10.3390","volume":"14","author":[{"given":"Jian","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Agro-Products Processing Science and Technology (Institute of Food Nutrition and Health), Sichuan Academy of Agricultural Sciences, Chengdu 610066, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9935-0275","authenticated-orcid":false,"given":"Litao","family":"Tong","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences\/Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manyou","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Agro-Products Processing Science and Technology (Institute of Food Nutrition and Health), Sichuan Academy of Agricultural Sciences, Chengdu 610066, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Agro-Products Processing Science and Technology (Institute of Food Nutrition and Health), Sichuan Academy of Agricultural Sciences, Chengdu 610066, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Food and Bioengineering, Xihua University, Chengdu 610039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junling","family":"Deng","sequence":"additional","affiliation":[{"name":"Institute of Agro-Products Processing Science and Technology (Institute of Food Nutrition and Health), Sichuan Academy of Agricultural Sciences, Chengdu 610066, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengzhang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences\/Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoya","family":"Xiang","sequence":"additional","affiliation":[{"name":"Institute of Agro-Products Processing Science and Technology (Institute of Food Nutrition and Health), Sichuan Academy of Agricultural Sciences, Chengdu 610066, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Xia","sequence":"additional","affiliation":[{"name":"Institute of Agro-Products Processing Science and Technology (Institute of Food Nutrition and Health), Sichuan Academy of Agricultural Sciences, Chengdu 610066, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155335","DOI":"10.1016\/j.phymed.2023.155335","article-title":"Multiomics profiling of the therapeutic effect of Dan-deng-tong-nao capsule on cerebral ischemia-reperfusion injury","volume":"128","author":"Shi","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"110807","DOI":"10.1016\/j.brainresbull.2023.110807","article-title":"Multi-parametric MRI assessment of melatonin regulating the polarization of microglia in rats after cerebral ischemia\/reperfusion injury","volume":"204","author":"Li","year":"2023","journal-title":"Brain Res. 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