Fengyan Zhao , Caiwang Peng , Hengli Li , Haodong Chen , Yantao Yang , Qidi Ai , Naihong Chen , Fang Liu
{"title":"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","authors":"Fengyan Zhao , Caiwang Peng , Hengli Li , Haodong Chen , Yantao Yang , Qidi Ai , Naihong Chen , Fang Liu","doi":"10.1016/j.jep.2023.116567","DOIUrl":null,"url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><p><span><em>Paeoniae Radix Rubra</em></span> (PRR), the root of <span><em>Paeonia</em><em> lactiflora</em></span> Pall. or <em>Paeonia veitchii</em><span> Lynch, has been widely used to promote blood circulation and eliminate blood stasis<span> in Chinese clinical practice, but its effect on cerebral ischemia is still rarely reported.</span></span></p></div><div><h3>Aim of the study</h3><p>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.</p></div><div><h3>Materials and methods</h3><p>The neuroprotective<span><span> effects of PRRE in Sprague-Dawley (SD) rats with middle cerebral artery occlusion<span> (MCAO) injury and mouse hippocampal neuronal cells (HT22 cell line) following oxidative stress were confirmed. The mechanism was investigated using immunohistochemical staining, western blotting, </span></span>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.</span></p></div><div><h3>Results</h3><p><span><span>The in vivo study showed that PRRE reduced infarct volume and improved neurological deficits in rats, and the expression of GPX4, FTH1, </span>Beclin1, LC3 II, and </span><em>p</em>-Akt was upregulated in the rat hippocampi. In addition, the vitro research indicated that PRRE can also alleviate H<sub>2</sub>O<sub>2</sub><span><span>-induced HT22 cell damage by regulating cytokines such as malondialdehyde (MDA), </span>reduced glutathione<span> (GSH) and reactive oxygen species<span><span><span><span> (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 </span>ferroptosis and autophagy are mainly defined as </span>albiflorin, </span>paeoniflorin<span>, benzoyl paeoniflorin, oleanolic acid, and hederagenin.</span></span></span></span></p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2023-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Paeoniae Radix Rubra extract attenuates cerebral ischemia injury by inhibiting ferroptosis and activating autophagy through the PI3K/Akt signalling pathway\",\"authors\":\"Fengyan Zhao , Caiwang Peng , Hengli Li , Haodong Chen , Yantao Yang , Qidi Ai , Naihong Chen , Fang Liu\",\"doi\":\"10.1016/j.jep.2023.116567\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Ethnopharmacological relevance</h3><p><span><em>Paeoniae Radix Rubra</em></span> (PRR), the root of <span><em>Paeonia</em><em> lactiflora</em></span> Pall. or <em>Paeonia veitchii</em><span> Lynch, has been widely used to promote blood circulation and eliminate blood stasis<span> in Chinese clinical practice, but its effect on cerebral ischemia is still rarely reported.</span></span></p></div><div><h3>Aim of the study</h3><p>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.</p></div><div><h3>Materials and methods</h3><p>The neuroprotective<span><span> effects of PRRE in Sprague-Dawley (SD) rats with middle cerebral artery occlusion<span> (MCAO) injury and mouse hippocampal neuronal cells (HT22 cell line) following oxidative stress were confirmed. The mechanism was investigated using immunohistochemical staining, western blotting, </span></span>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.</span></p></div><div><h3>Results</h3><p><span><span>The in vivo study showed that PRRE reduced infarct volume and improved neurological deficits in rats, and the expression of GPX4, FTH1, </span>Beclin1, LC3 II, and </span><em>p</em>-Akt was upregulated in the rat hippocampi. In addition, the vitro research indicated that PRRE can also alleviate H<sub>2</sub>O<sub>2</sub><span><span>-induced HT22 cell damage by regulating cytokines such as malondialdehyde (MDA), </span>reduced glutathione<span> (GSH) and reactive oxygen species<span><span><span><span> (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 </span>ferroptosis and autophagy are mainly defined as </span>albiflorin, </span>paeoniflorin<span>, benzoyl paeoniflorin, oleanolic acid, and hederagenin.</span></span></span></span></p></div><div><h3>Conclusion</h3><p>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.</p></div>\",\"PeriodicalId\":15761,\"journal\":{\"name\":\"Journal of ethnopharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2023-05-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of ethnopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S037887412300435X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S037887412300435X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Paeoniae Radix Rubra extract attenuates cerebral ischemia injury by inhibiting ferroptosis and activating autophagy through the PI3K/Akt signalling pathway
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.
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.