Comprehensive metagenomic and lipidomic analysis showed that baicalin could improve depressive behaviour in atherosclerotic mice by inhibiting nerve cell ferroptosis

作者：Peng Ren, Yulong Zhao, Xue Li, Jing Xie, Xing-Xing Liao, Qiang Luo, Xu Liu, Jiameng Li, Yu Fan, Xinyi Cheng, Xinyao Fu, Junjie Zhou, Xiaoyun Wu · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1599570 · 被引用次数：9 · 研究领域：Ferroptosis and cancer prognosis、Immune cells in cancer、Immune responses and vaccinations

Background Atherosclerosis (AS) concomitant depression is a serious clinical problem with unclear mechanisms of co-morbidity. Baicalin (BA) can resist atherosclerosis and depression by regulating intestinal flora and host lipid metabolism. Therefore, based on intestinal microorganisms and lipid metabolism, this study explored the mechanism of baicalin against AS concomitant depression. Methods 16 C57BL/6 mice were fed with normal diet as blank control group. 48 ApoE -/- mice were randomly divided into 3 groups (model group and BAL, BAH two treatment groups). The mouse model of atherosclerosis concomitant depression was established by high-fat feeding combined with restraint stimulation for 16 weeks. Behavioural experiments and biochemical indexes were used to detect the antidepressant effect and anti-atherosclerosis effect of baicalin. Metagenomic sequencing technology combined with metabolomics analysis was used to detect the effects of BA on intestinal microflora structure and brain lipids in AS co-depressed mice. Erastin was used to induce HT-22 hippocampal neurons to construct a model of ferroptosis. The inhibition of baicalin on ferrotosis was verified by detecting the cell viability, ROS production, and expression levels of glutathione, SLC7A11, GPX4 and ACSL4 in each group. Results Baicalin could effectively improve the indexes of AS co-depressed mice, and the results of metagenomics and lipidomics showed that there were disorders of intestinal flora represented by Hel...