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Functional validation with genetic manipulation shows Antro promotes DNA methylation via DNA methyltransferase activity, downregulating Tlr4 and inhibiting NF-κB signaling, resulting in reduced IL-1β production.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/antroquinonol-reduces-il-1-production-in-macrophages-through-enhancing-the-dna-methylation-of-tlr4/454859/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/antroquinonol-reduces-il-1-production-in-macrophages-through-enhancing-the-dna-methylation-of-tlr4/454859.png","ImageObject",300,407,{"name":42,"@type":43},"Adam","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-08","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the main anti-inflammatory effect of antroquinonol on macrophages?","Question",{"text":63,"@type":64},"Antroquinonol attenuates IL-1β production in macrophages by suppressing inflammatory signaling pathways.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does antroquinonol regulate Tlr4 expression?",{"text":68,"@type":64},"It enhances DNA methylation processes by increasing DNA methyltransferase activity, leading to suppression of Tlr4 expression.",{"name":70,"@type":61,"acceptedAnswer":71},"Which signaling pathway is implicated in the reduction of IL-1β?",{"text":72,"@type":64},"The study links Tlr4 downregulation to inhibition of NF-κB signaling, which ultimately reduces IL-1β 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\nEDITED BY  \nJing Gao,  \nNational Engineering Research Center for Oil Tea, China  \nREVIEWED BY  \nChi-Heng Wu,  \nDren Bio, Inc., United States Guomei Quan,  \nGansu Agricultural University, China  \n*CORRESPONDENCE  \nJiahao Mo  \n [mjh874540259@163.com](mjh874540259@163.com)[ ](mjh874540259@163.com)Kaijun Wang  \n [kj-wang@foxmail.com](kj-wang@foxmail.com)  \nRECEIVED 09 November 2025  \nREVISED 21 November 2025  \nACCEPTED 01 December 2025  \nPUBLISHED 24 December 2025  \nCITATION  \nBin P, Fu Z, Wang Z, Hung I, Liu C, Peng W, Wang K and Mo J (2025) Antroquinonol reduces IL-1β production in macrophages through enhancing the DNA methylation of Tlr4 . Front. Nutr. 12:1742566 .  \ndoi: 10.3389/fnut.2025.1742566  \nCOPYRIGHT  \n© 2025 Bin, Fu, Wang, Hung, Liu, Peng, Wang and Mo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nAntroquinonol reduces IL-1β production in macrophages through enhancing the DNA methylation of Tlr4  \nPeng Bin1 , Zhengyang Fu1 , Zixu Wang2 , Ifen Hung2 ,  \nChunxue Liu2 , Wenjin Peng1 , Kaijun Wang3* and Jiahao Mo3,4*  \n1 State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou, China, 2Anyou Biotechnology Group Co. LTD, Taicang, China,  \n3 Hunan Provincial Key Laboratory of the Traditional Chinese Medicine Agricultural Biogenomics, Changsha Medical University, Changsha, China, 4 College of Veterinary Medicine, Hunan Agricultural University, Changsha, China  \nIntroduction: Macrophages represent one of the most pivotal immune cells in the innate immune responses of weaned piglets. Emerging studies have revealed that numerous plant- or fungal-derived extracts significantly modulate macrophage functions. Antroquinonol (Antro), a characteristic triterpenoid compound isolated from Antrodia camphorata, has been extensively documented for its anti-inflammatory properties, but the precise mechanisms remain unclear.  \nMethods: In this study, we established a macrophage polarization model in vitro, and evaluated the impact of Antro on inflammatory cytokine production in M1 macrophages. The expression of inflammatory pathway components was then measured to identify the specific targets regulated by Antro, and genetic manipulation approaches were further applied to validate these targets.  \nResults: Antro enhances the enzymatic activities of DNA methyltransferases and facilitates DNA methylation-mediated suppression of Tlr4 expression, thereby inhibiting NF-κB signaling, ultimately attenuating IL-1β production in macrophages.  \nConclusion: Our study elucidates a multi-pathway for the anti-inflammatory effects of Antro, significantly enriching the theoretical framework of natural product-mediated immunomodulation (particularly plant/fungal extracts) . These findings provide critical scientific support for developing A. camphorata-derived fermentation products as novel feed additives to enhance immune function in swine production.  \nKEYWORDS  \nAntrodia camphorata, antroquinonol, macrophage, DNA methylation, IL-1β  \n1 Introduction  \nAs the key components of innate immunity, macrophages exhibit high heterogeneity and plasticity. They can polarize into classically activated (M1) or alternatively activated (M2) subtypes in response to environmental stimuli, thereby participating in immune regulation, tissue repair, and metabolic processes ( 1) . During early inflammation, M1 macrophages secrete pro-inflammatory cytokines [e.g., interleukin (IL)-1β, IL-6, IL-12, tumor necrosis facto","cbCaiqSwNdlU7zC8","https://ap.wps.com/l/cbCaiqSwNdlU7zC8","pdf",8263389,11,"English","# Introduction\n## Macrophage polarization and inflammatory cytokines\n## Epigenetic regulation and DNA methylation\n# Methods\n## Macrophage polarization model and cytokine evaluation\n## Pathway target identification and genetic validation\n# Results\n## DNA methyltransferase activity and Tlr4 methylation\n## NF-κB signaling inhibition and IL-1β reduction\n# Conclusion","[{\"question\":\"What is the main anti-inflammatory effect of antroquinonol on macrophages?\",\"answer\":\"Antroquinonol attenuates IL-1β production in macrophages by suppressing inflammatory signaling pathways.\"},{\"question\":\"How does antroquinonol regulate Tlr4 expression?\",\"answer\":\"It enhances DNA methylation processes by increasing DNA methyltransferase activity, leading to suppression of Tlr4 expression.\"},{\"question\":\"Which signaling pathway is implicated in the reduction of IL-1β?\",\"answer\":\"The study links Tlr4 downregulation to inhibition of NF-κB signaling, which ultimately reduces IL-1β production.\"}]","Antroquinonol reduces IL-1β production in macrophages through enhancing the DNA methylation of Tlr4 | PDF",1790741516,28]