Paeoniae Radix Rubra extract attenuates cerebral ischemia injury by inhibiting ferroptosis and activating autophagy through the PI3K/Akt signalling pathway

IF 4.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of ethnopharmacology Pub Date : 2023-05-11 DOI:10.1016/j.jep.2023.116567

Fengyan Zhao , Caiwang Peng , Hengli Li , Haodong Chen , Yantao Yang , Qidi Ai , Naihong Chen , Fang Liu

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引用次数: 1

Abstract

Ethnopharmacological relevance

Paeoniae Radix Rubra (PRR), the root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch, has been widely used to promote blood circulation and eliminate blood stasis in Chinese clinical practice, but its effect on cerebral ischemia is still rarely reported.

Aim of the study

The present study aimed to assess the potential therapeutic possibilities of the extract of PRR (PRRE) on cerebral ischemia, further exploring the underlying mechanism, and preliminary screening of the corresponding active components.

Materials and methods

The neuroprotective effects of PRRE in Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO) injury and mouse hippocampal neuronal cells (HT22 cell line) following oxidative stress were confirmed. The mechanism was investigated using immunohistochemical staining, western blotting, transmission electron microscopy (TEM), and immunofluorescence. The active components of PRRE were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and molecular docking.

Results

The in vivo study showed that PRRE reduced infarct volume and improved neurological deficits in rats, and the expression of GPX4, FTH1, Beclin1, LC3 II, and p-Akt was upregulated in the rat hippocampi. In addition, the vitro research indicated that PRRE can also alleviate H₂O₂-induced HT22 cell damage by regulating cytokines such as malondialdehyde (MDA), reduced glutathione (GSH) and reactive oxygen species (ROS), and the expressions of GPX4 and Beclin1 were observed to be elevated. The PI3K/Akt signalling pathway was inhibited by LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K). Furthermore, the effective components of PRRE in regulating ferroptosis and autophagy are mainly defined as albiflorin, paeoniflorin, benzoyl paeoniflorin, oleanolic acid, and hederagenin.

Conclusion

PRRE exerts neuroprotective effects against cerebral ischaemic injury by inhibiting ferroptosis and activating autophagy through the PI3K/Akt signalling pathway. This study provides an experimental basis for the potential application of PRRE as a novel therapeutic drug, and PI3K/Akt-associated ferroptosis and autophagy as therapeutic targets for cerebral ischemia.

Abstract Image

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赤芍提取物通过PI3K/Akt信号通路抑制铁凋亡，激活自噬，减轻脑缺血损伤

芍药根芍药的民族药理学意义。黄芍在我国临床已广泛应用于活血化瘀，但其对脑缺血的治疗作用仍鲜有报道。本研究旨在评估PRRE提取物(PRRE)治疗脑缺血的潜在可能性，进一步探讨其作用机制，并初步筛选相应的活性成分。材料和方法证实PRRE对脑中动脉闭塞(MCAO)损伤SD大鼠和氧化应激后小鼠海马神经元细胞(HT22细胞系)的神经保护作用。采用免疫组织化学染色、免疫印迹、透射电镜(TEM)和免疫荧光等方法研究其作用机制。采用液相色谱-串联质谱(LC-MS/MS)和分子对接技术对PRRE的有效成分进行分析。结果体内研究显示，PRRE可减少大鼠梗死体积，改善神经功能缺损，并上调大鼠海马组织中GPX4、FTH1、Beclin1、lc3ii和p-Akt的表达。此外，体外研究表明，PRRE还可通过调节丙二醛(MDA)、还原谷胱甘肽(GSH)、活性氧(ROS)等细胞因子，减轻h2o2诱导的HT22细胞损伤，GPX4、Beclin1表达升高。PI3K/Akt信号通路被磷酸肌苷激酶(PI3K)抑制剂LY294002抑制。此外，PRRE调节铁凋亡和自噬的有效成分主要为芍药苷、芍药苷、苯甲酰芍药苷、齐ole果酸和hederagenin。结论prre通过PI3K/Akt信号通路抑制铁凋亡，激活自噬，对脑缺血损伤具有神经保护作用。本研究为PRRE作为一种新型治疗药物的潜在应用，以及PI3K/ akt相关的铁凋亡和自噬作为脑缺血的治疗靶点提供了实验基础。

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 ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.