Hypericin Regulates Inflammation Levels and Improves Depressive Symptoms in Rats With Post-Stroke Depression Through the MEK/ERK/CREB Pathway

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-05-18 DOI:10.1002/jbt.70295

Kui Jia, Wenlong Li, Yifan Li, Lingling Qian

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引用次数: 0

Abstract

Objective

To investigate the effect of hypericin on ameliorating depressive behaviour in post-stroke depression (PSD) rats.

Methods

Rats underwent a middle cerebral artery occlusion and chronic mild stress for 28 days to create a PSD model. Behavioural tests included the open field test (OFT) and the elevated plus maze test. Hypericin at a low (100 mg/kg) and a high (400 mg/kg) dose was administered via gavage. Lipopolysaccharide (LPS) was used to establish a microglia-injury model, with hypericin treatment at 0.25, 0.5, 1, and 2 μmol/L, and ELISA was used to measure serotonin (5-HT), interleukin (IL)-6 and IL-10 levels. Additionally, Western blot analysis and immunohistochemistry analysed protein levels and the expression of iNOS and Arg-1 in the hippocampus.

Results

Following the PSD model preparation, the rats showed substantially reduced movement in the OFT and spent less time in the open arms of the elevated plus maze, whereas treatment with hypericin and fluoxetine improved depressive behaviour in these tests. In addition, hypericin decreased IL-6, increased IL-10 and 5-HT and enhanced p-MEK/MEK, p-ERK/ERK and p-CREB/CREB expression in the serum of the PSD rats and the LPS cell model. Hypericin also reduced iNOS but increased Arg-1 expression in the PSD rat hippocampus.

Conclusion

Hypericin promotes M2 microglial polarisation, reduces inflammation and improves depressive behaviour in PSD rats by activating the MEK/ERK/CREB pathway.

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金丝桃素通过MEK/ERK/CREB通路调节脑卒中后抑郁大鼠炎症水平并改善抑郁症状

目的探讨金丝桃素对脑卒中后抑郁大鼠抑郁行为的改善作用。方法大鼠大脑中动脉闭塞和慢性轻度应激28 d建立PSD模型。行为学测试包括空地测试（OFT）和高架加迷宫测试。灌胃给予低剂量（100 mg/kg）和高剂量（400 mg/kg）金丝桃素。采用脂多糖（LPS）建立小胶质细胞损伤模型，分别给予0.25、0.5、1、2 μmol/L金丝桃素处理，ELISA法检测血清素（5-HT）、白细胞介素(IL)-6、IL-10水平。Western blot和免疫组化分析海马组织中iNOS和Arg-1的表达及蛋白水平。结果在PSD模型制备后，大鼠在OFT中的运动明显减少，在高架+迷宫的张开双臂中花费的时间减少，而金丝桃素和氟西汀治疗在这些测试中改善了抑郁行为。金丝桃素可降低PSD大鼠及LPS细胞模型血清中IL-6、IL-10、5-HT的表达，提高p-MEK/MEK、p-ERK/ERK、p-CREB/CREB的表达。金丝桃素还能降低PSD大鼠海马中iNOS的表达，增加Arg-1的表达。结论金丝桃素通过激活MEK/ERK/CREB通路，促进PSD大鼠M2小胶质细胞极化，减轻炎症，改善抑郁行为。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Biochemical and Molecular Toxicology 生物-毒理学

CiteScore

5.80

自引率

2.80%

发文量

277

审稿时长

6-12 weeks

期刊介绍： The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.