Jia Siqi, Wang Ruijuan, Zhang Dongyan, Guan Zhiyu, Ding Tingting, Zhang Jingnan, Zhao Xiujuan
Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 194 Xuefu Road, Harbin, Heilongjiang 150081, China.
Food Funct. 2023 Feb 6;14(3):1726-1739. doi: 10.1039/d2fo03277e.
Depression is the most prevalent psychiatric disease, and its pathogenesis is still unclear. Currently, studies on the pathogenesis of depression are mainly focused on the brain. The liver can modulate brain function the liver-brain axis, indicating that the liver plays an important role in the development of depression. This study aims to explore the protective effect of quercetin against chronic unpredictable mild stress (CUMS)-induced metabolic changes and the corresponding mechanisms in the rat liver based on untargeted metabolomics technology. In this study, 96 male rats were divided into six groups: control, different doses of quercetin (10 mg per kg bw or 50 mg per kg bw), CUMS, and CUMS + different doses of quercetin. After 8 weeks of CUMS modeling, the liver samples were collected for metabolomics analysis. A total of 17 altered metabolites were identified, including D-glutamic acid, -adenosylmethionine, lithocholylglycine, L-homocystine, prostaglandin PGE2, leukotriene E4, cholic acid, 5-methyltetrahydrofolic acid, taurochenodeoxycholic acid, -adenosylhomocysteine, deoxycholic acid, folic acid, L-methionine, leukotriene C5, estriol-17-glucuronide, PE, and PC, indicating that methionine metabolism, bile acid metabolism, and phosphatidylcholine biosynthesis are the major pathways involved in CUMS-induced hepatic metabolic disorders. Hepatic methylation damage may play a role in the pathophysiology of depression, as evidenced by the first discovery of the abnormality of hepatic methionine metabolism. Abnormal changes in hepatic bile acids may provide stronger evidence for depression pathogenesis involving the microbiota-gut-brain axis, suggesting that the liver is involved in depression development and may be a treatment target. The quercetin treatment alleviated the CUMS-induced liver metabolism disorder, suggesting that quercetin may protect against depression by regulating liver metabolism.
抑郁症是最常见的精神疾病，其发病机制仍不清楚。目前，关于抑郁症发病机制的研究主要集中在大脑。肝脏可通过肝脑轴调节大脑功能，这表明肝脏在抑郁症的发生发展中起重要作用。本研究旨在基于非靶向代谢组学技术，探讨槲皮素对慢性不可预测温和应激（CUMS）诱导的大鼠肝脏代谢变化的保护作用及相应机制。在本研究中，96只雄性大鼠被分为六组：对照组、不同剂量槲皮素组（10mg/kg体重或50mg/kg体重）、CUMS组以及CUMS+不同剂量槲皮素组。经过8周的CUMS建模后，采集肝脏样本进行代谢组学分析。共鉴定出17种变化的代谢物，包括D-谷氨酸、S-腺苷甲硫氨酸、甘氨石胆酸、L-高半胱氨酸、前列腺素PGE2、白三烯E4、胆酸、5-甲基四氢叶酸、牛磺鹅去氧胆酸、S-腺苷同型半胱氨酸、脱氧胆酸、叶酸、L-甲硫氨酸、白三烯C5、雌三醇-17-葡萄糖醛酸、PE和PC，表明甲硫氨酸代谢、胆汁酸代谢和磷脂酰胆碱生物合成是CUMS诱导的肝脏代谢紊乱的主要途径。肝脏甲基化损伤可能在抑郁症的病理生理学中起作用，肝脏甲硫氨酸代谢异常的首次发现证明了这一点。肝脏胆汁酸的异常变化可能为涉及微生物群-肠道-脑轴的抑郁症发病机制提供更有力的证据，表明肝脏参与抑郁症的发展，可能是一个治疗靶点。槲皮素治疗减轻了CUMS诱导的肝脏代谢紊乱，表明槲皮素可能通过调节肝脏代谢来预防抑郁症。
