异环大肾改善大鼠睡眠剥夺引起的神经化学破坏和神经炎症中的海马铁下垂。

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-01-01 DOI:10.1016/j.phymed.2024.156306

Ao Yan , Zhejin Li , Yuanwei Gao , Fanglong Hu , Shuo Han , Fengjie Liu , Zhongcheng Liu , Jinting Chen , Chunmao Yuan , Chengyan Zhou

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引用次数: 0

摘要

背景：睡眠剥夺（SLD）是一种广泛存在的疾病，它会破坏生理功能，并可能增加死亡风险。缬草（Valeriana officinalis）是一种以镇静和催眠特性而闻名的传统草药，它含有一种新分离的活性化合物异环大肾（IG）。然而，关于IG治疗SLD的潜力的研究仍然有限。方法：本研究从缬草中提取IG并对其进行表征，采用对氯苯丙氨酸（PCPA）建立大鼠SLD模型。通过行为试验和病理研究来评估IG对SLD的影响，并利用转录组学和代谢组学分析来研究其潜在机制。结果：IG显著改善了大鼠行为测试中的认知能力，改善了海马和大脑皮层的组织学损伤。IG处理增加了SLD大鼠脑源性神经营养因子（BDNF）和神经递质如血清素（5-HT）的水平。此外，IG直接作用于TFRC，从而改善海马体内的铁代谢。综合转录组学和代谢组学分析显示，IG的改善源于铁代谢、胆固醇代谢和谷胱甘肽代谢异常的缓解，从而减少了SLD引起的海马氧化应激、铁下沉和神经炎症。结论：总的来说，这些发现表明IG有可能改善SLD引起的神经损伤和认知障碍，为防止SLD的不良反应提供了一种新的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Isobicyclogermacrenal ameliorates hippocampal ferroptosis involvement in neurochemical disruptions and neuroinflammation induced by sleep deprivation in rats

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Isobicyclogermacrenal ameliorates hippocampal ferroptosis involvement in neurochemical disruptions and neuroinflammation induced by sleep deprivation in rats

Background

Sleep deprivation (SLD) is a widespread condition that disrupts physiological functions and may increase mortality risk. Valeriana officinalis, a traditional medicinal herb known for its sedative and hypnotic properties, contains isobicyclogermacrenal (IG), a newly isolated active compound. However, research on the therapeutic potential of IG for treating SLD remains limited.

Methods

In this study, IG was extracted and characterized from Valeriana officinalis, and an SLD model was established in rats using p-chlorophenylalanine (PCPA). Behavioral tests and pathological studies were conducted to assess the effects of IG on SLD, and transcriptomic and metabolomic analyses were utilized to investigate its underlying mechanisms.

Results

IG administration significantly improved the cognitive performance of SLD rats in behavioral tests and ameliorated histological injuries in the hippocampus and cerebral cortex. IG treatment increased the levels of brain-derived neurotrophic factor (BDNF) and neurotransmitters such as serotonin (5-HT) in SLD rats. Additionally, IG directly targets TFRC, thereby improving iron metabolism in the hippocampus. Comprehensive transcriptomic and metabolomic analyses revealed that the improvements from IG stemmed from the mitigation of abnormalities in iron metabolism, cholesterol metabolism, and glutathione metabolism, leading to reduced oxidative stress, ferroptosis, and neuroinflammation in the hippocampus caused by SLD.

Conclusions

Collectively, these findings suggest that IG has the potential to ameliorate neurological damage and cognitive impairment caused by SLD, offering a novel strategy for protection against the adverse effects of SLD.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.