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Although pharmacologic inhibition is promising, clinically usable inhibitors remain limited, including the classical ferrostatin-1 (Fer-1). Ginsenoside Rb1 (Rb1), a major active component of Panax ginseng, has shown ferroptosis suppression in non-renal tissues, motivating evaluation of its role and mechanism in AKI.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/ginsenoside-rb1-targets-the-nrf2-ppar-acsl4-axis-to-inhibit-ptecs-ferroptosis/458691/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/ginsenoside-rb1-targets-the-nrf2-ppar-acsl4-axis-to-inhibit-ptecs-ferroptosis/458691.png","ImageObject",300,407,{"name":92,"@type":93},"Aran","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-09","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",16,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What role does ferroptosis play in acute kidney injury (AKI)?","Question",{"text":113,"@type":114},"Ferroptosis is described as a predominant driver of acute tubular necrosis in AKI, driven by iron-dependent accumulation of lethal lipid peroxides.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Why are ferroptosis inhibitors such as ferrostatin-1 limited clinically?",{"text":118,"@type":114},"Fer-1 is noted to have limitations including poor pharmacokinetics and incomplete pathway coverage.",{"name":120,"@type":111,"acceptedAnswer":121},"How does Rb1 inhibit ferroptosis according to the described mechanism?",{"text":122,"@type":114},"Rb1 is reported to suppress lipid peroxidation by activating the NRF2-PPARγ-ACSL4 axis, with NRF2 verified as a direct target.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},458691,1791037661,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},137455076865,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Tan et al. Chinese Medicine (2026) 21:19 [https://doi.org/10.1186/s13020-025-01292-x](https://doi.org/10.1186/s13020-025-01292-x)  \nChinese Medicine  \n RESEARCH Open Access  \nGinsenoside Rb1  \ntargets  \nthe NRF2-PPARγ-ACSL4 axis to inhibit PTECs ferroptosis  \nBinghong Tan1†, Zhifen Wu1†, Suwei Wang1, Wei Tan1, Lirong Lin1, Xujia Yang1, Luquan Zheng1, Jing Li2, Ke Li3, Jurong Yang1* and Li Li4*  \nAbstract  \nBackground Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a critical pathological mechanism in acute kidney injury (AKI) . While pharmacologic targeting offerroptosis holds therapeutic potential, clinically applicable inhibitors remain elusive, with even the classical inhibitor ferrostatin-1 (Fer-1) demonstrating limitations. Ginsenoside Rb1 (Rb1), a major active component of Panax ginseng, has recently been shown to inhibit ferroptosis in non-renal tissues. This study aimed to investigate the role and mechanism of Rb1 in treating AKI.  \nMethods The protective and anti-ferroptotic effects of Rb1 on AKI were evaluated by assessing renal function, tissue damage, inflammation, ferrous iron, glutathione, malondialdehyde, and ferroptosis markers in C57BL/6 mice, as well as cell viability and ferroptosis-related indicators in HK-2 cells. Network pharmacology and molecular docking were employed to identify Rb1’s target proteins. Transcriptome sequencing predicted further mechanisms underlying its anti-ferroptotic effects, which were subsequently validated through in vivo and in vitro experiments.  \nResults The experimental results demonstrated that Rb1 administration significantly ameliorated renal dysfunction, attenuated tubular necrosis and inflammatory responses, while markedly suppressing ferroptosis-related indicators. Strikingly, Rb1 exhibited superior efficacy to Fer-1 in preventing ferroptosis in proximal tubular epithelial cells (PTECs) in vitro. Nuclear factor erythroid 2-related factor 2 (NRF2) was verified as a direct target for Rb1’s ferroptosis-inhibitory effect. Mechanistic studies revealed that Rb1 selectively inhibits lipid peroxidation—the biochemical hallmark offerroptosis—by activating the NRF2-PPARγ-ACSL4 axis.  \nConclusion Given its established safety profile in human use, Rb1 represents a potential therapeutic agent for preventing and treating AKI, providing scientific evidence for its application in anti-ferroptosis therapy.  \nKeywords Ginsenoside Rb1, Ferroptosis, PTEC, NRF2, PPARγ, ACSL4  \n†Binghong Tan and Zhifen Wu contributed equally.  \n*Correspondence:  \nJurong Yang [650230@hospital.cqmu.edu.cn](650230@hospital.cqmu.edu.cn)[ ](650230@hospital.cqmu.edu.cn)Li Li  \n[guilinlily3@i.smu.edu.cn](guilinlily3@i.smu.edu.cn)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[http://creativeco](http://creativeco)[mmons.or","cbCaidz89QwFGYMO","https://ap.wps.com/l/cbCaidz89QwFGYMO","pdf",15975396,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Introduction\n## AKI and regulated cell death\n## Ferroptosis mechanisms and clinical challenges\n## Rb1 therapeutic rationale","[{\"question\":\"What role does ferroptosis play in acute kidney injury (AKI)?\",\"answer\":\"Ferroptosis is described as a predominant driver of acute tubular necrosis in AKI, driven by iron-dependent accumulation of lethal lipid peroxides.\"},{\"question\":\"Why are ferroptosis inhibitors such as ferrostatin-1 limited clinically?\",\"answer\":\"Fer-1 is noted to have limitations including poor pharmacokinetics and incomplete pathway coverage.\"},{\"question\":\"How does Rb1 inhibit ferroptosis according to the described mechanism?\",\"answer\":\"Rb1 is reported to suppress lipid peroxidation by activating the NRF2-PPARγ-ACSL4 axis, with NRF2 verified as a direct target.\"}]","Ginsenoside Rb1 - targets the NRF2-PPARγ-ACSL4 axis to inhibit PTECs ferroptosis | PDF",1790754091,48]