Jia Sun , Keke Zhao , Wenyue Zhang , Chen Guo , Hua Liu
{"title":"蜕皮激素通过 ACSL4 抑制神经元中的铁氧化，从而改善急性缺血性中风诱发的氧化损伤","authors":"Jia Sun , Keke Zhao , Wenyue Zhang , Chen Guo , Hua Liu","doi":"10.1016/j.jep.2024.118204","DOIUrl":null,"url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><p>Acute ischemic stroke (AIS) is a prominent cause of disability and mortality around the world. <em>Achyranthes bidentata</em> Blume, a regularly prescribed traditional Chinese herb, plays a significant role in traditional Chinese stroke therapy due to its ability to promote blood circulation and remove stasis. Ecdysterone (EDS) is one of the key active components in <em>Achyranthes bidentata</em> Blume, which exhibits antioxidant and anti-cerebral hypoxia properties. However, whether EDS improves AIS and the mechanism of action of AIS is still unclear.</p></div><div><h3>Aim of the study</h3><p>The objective of this study was to observe whether EDS ameliorates oxidative damage caused by AIS by inhibiting ferroptosis in neurons via ACSL4.</p></div><div><h3>Materials and methods</h3><p><em>In vivo</em>, the Middle cerebral artery occlusion (MCAO) rat model was established for research. After treatment with EDS, Neurologic score, TTC, HE and FJC staining were performed, followed by measurements of oxidative stress-related indicators, the content of Fe<sup>2+</sup>, iron deposition levels and expression of ACSL4, NCOA4 and FTH1 in brain tissue. <em>In vitro</em>, oxygen-glucose deprivation and reperfusion (OGD/R) cell model was established. After treatment with EDS, cell viability, oxidative stress-related indicators, the content of Fe<sup>2+</sup> and expression of ACSL4, NCOA4 and FTH1 were detected. In addition, the overexpression of ACSL4 and CETSA technology further elucidated that EDS improves AIS through ACSL4.</p></div><div><h3>Results</h3><p>The results showed that the treatment of EDS could improve the oxidative damage of MCAO rats by inhibiting ferroptosis, and then improve AIS. Importantly, EDS inhibited ferroptosis via ACSL4, thereby inhibiting oxidative stress in MCAO rats or OGD/R-induced PC12 cells.</p></div><div><h3>Conclusions</h3><p>These results provide evidence that EDS ameliorates oxidative damage caused by AIS by inhibiting ferroptosis via ACSL4, and provide new insights into the potential use of EDS as an effective drug development candidate for AIS.</p></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"331 ","pages":"Article 118204"},"PeriodicalIF":5.4000,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ecdysterone improves oxidative damage induced by acute ischemic stroke via inhibiting ferroptosis in neurons through ACSL4\",\"authors\":\"Jia Sun , Keke Zhao , Wenyue Zhang , Chen Guo , Hua Liu\",\"doi\":\"10.1016/j.jep.2024.118204\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Ethnopharmacological relevance</h3><p>Acute ischemic stroke (AIS) is a prominent cause of disability and mortality around the world. <em>Achyranthes bidentata</em> Blume, a regularly prescribed traditional Chinese herb, plays a significant role in traditional Chinese stroke therapy due to its ability to promote blood circulation and remove stasis. Ecdysterone (EDS) is one of the key active components in <em>Achyranthes bidentata</em> Blume, which exhibits antioxidant and anti-cerebral hypoxia properties. However, whether EDS improves AIS and the mechanism of action of AIS is still unclear.</p></div><div><h3>Aim of the study</h3><p>The objective of this study was to observe whether EDS ameliorates oxidative damage caused by AIS by inhibiting ferroptosis in neurons via ACSL4.</p></div><div><h3>Materials and methods</h3><p><em>In vivo</em>, the Middle cerebral artery occlusion (MCAO) rat model was established for research. After treatment with EDS, Neurologic score, TTC, HE and FJC staining were performed, followed by measurements of oxidative stress-related indicators, the content of Fe<sup>2+</sup>, iron deposition levels and expression of ACSL4, NCOA4 and FTH1 in brain tissue. <em>In vitro</em>, oxygen-glucose deprivation and reperfusion (OGD/R) cell model was established. After treatment with EDS, cell viability, oxidative stress-related indicators, the content of Fe<sup>2+</sup> and expression of ACSL4, NCOA4 and FTH1 were detected. In addition, the overexpression of ACSL4 and CETSA technology further elucidated that EDS improves AIS through ACSL4.</p></div><div><h3>Results</h3><p>The results showed that the treatment of EDS could improve the oxidative damage of MCAO rats by inhibiting ferroptosis, and then improve AIS. Importantly, EDS inhibited ferroptosis via ACSL4, thereby inhibiting oxidative stress in MCAO rats or OGD/R-induced PC12 cells.</p></div><div><h3>Conclusions</h3><p>These results provide evidence that EDS ameliorates oxidative damage caused by AIS by inhibiting ferroptosis via ACSL4, and provide new insights into the potential use of EDS as an effective drug development candidate for AIS.</p></div>\",\"PeriodicalId\":15761,\"journal\":{\"name\":\"Journal of ethnopharmacology\",\"volume\":\"331 \",\"pages\":\"Article 118204\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2024-04-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of ethnopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378874124005038\",\"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/S0378874124005038","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Ecdysterone improves oxidative damage induced by acute ischemic stroke via inhibiting ferroptosis in neurons through ACSL4
Ethnopharmacological relevance
Acute ischemic stroke (AIS) is a prominent cause of disability and mortality around the world. Achyranthes bidentata Blume, a regularly prescribed traditional Chinese herb, plays a significant role in traditional Chinese stroke therapy due to its ability to promote blood circulation and remove stasis. Ecdysterone (EDS) is one of the key active components in Achyranthes bidentata Blume, which exhibits antioxidant and anti-cerebral hypoxia properties. However, whether EDS improves AIS and the mechanism of action of AIS is still unclear.
Aim of the study
The objective of this study was to observe whether EDS ameliorates oxidative damage caused by AIS by inhibiting ferroptosis in neurons via ACSL4.
Materials and methods
In vivo, the Middle cerebral artery occlusion (MCAO) rat model was established for research. After treatment with EDS, Neurologic score, TTC, HE and FJC staining were performed, followed by measurements of oxidative stress-related indicators, the content of Fe2+, iron deposition levels and expression of ACSL4, NCOA4 and FTH1 in brain tissue. In vitro, oxygen-glucose deprivation and reperfusion (OGD/R) cell model was established. After treatment with EDS, cell viability, oxidative stress-related indicators, the content of Fe2+ and expression of ACSL4, NCOA4 and FTH1 were detected. In addition, the overexpression of ACSL4 and CETSA technology further elucidated that EDS improves AIS through ACSL4.
Results
The results showed that the treatment of EDS could improve the oxidative damage of MCAO rats by inhibiting ferroptosis, and then improve AIS. Importantly, EDS inhibited ferroptosis via ACSL4, thereby inhibiting oxidative stress in MCAO rats or OGD/R-induced PC12 cells.
Conclusions
These results provide evidence that EDS ameliorates oxidative damage caused by AIS by inhibiting ferroptosis via ACSL4, and provide new insights into the potential use of EDS as an effective drug development candidate for AIS.
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.
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