{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:27:24Z","timestamp":1783344444749,"version":"3.54.6"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["\u7f16\u53f7 82104772"],"award-info":[{"award-number":["\u7f16\u53f7 82104772"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M721067"],"award-info":[{"award-number":["2022M721067"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018551","name":"Science and Technology Innovation Talents in Universities of Henan Province","doi-asserted-by":"publisher","award":["222102310502"],"award-info":[{"award-number":["222102310502"]}],"id":[{"id":"10.13039\/501100018551","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Taohong Siwu Decoction (THSW Decoction), a classic formula for treating blood stasis, has demonstrated significant clinical efficacy in the treatment of hepatic fibrosis. However, its primary active components and mechanisms of action remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, a carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)-induced hepatic fibrosis mouse model was established to evaluate THSW Decoction\u2019s therapeutic effects. Ultra-high performance liquid chromatography-quadrupole\/Orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap HRMS) was employed to identify the main prototype chemical components of THSW Decoction in the blood, while non-targeted metabolomics analysis was performed using a Waters Synapt G2-Si QTOF mass spectrometer (Synapt G2-Si QTOF HRMS system). Network pharmacology and metabolomic data were integrated to elucidate the therapeutic targets, differential metabolites, and signaling pathways of THSW Decoction. Molecular docking and binding affinity predictions between key targets and principal compounds were performed using PyMOL software. Furthermore, molecular dynamics simulations were conducted to evaluate the structural stability and binding interactions. Finally, core targets were validated <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>THSW Decoction effectively reduced CCl<jats:sub>4<\/jats:sub>-induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, alleviating liver inflammation and collagen deposition. Forty-five blood components were detected, with 616 corresponding drug targets identified, including 419 overlapping targets for anti-hepatic fibrosis. The core protein-protein interaction (PPI) network comprised 59 nodes and 570 edges. Enrichment analysis revealed that THSW Decoction\u2019s blood components primarily modulated biological processes such as positive regulation of response to external stimuli and oxygen content. Key signaling pathways included PI3K-Akt, estrogen, relaxin, and MAPK. Non-targeted metabolomics identified 148 differential metabolites between the model and normal groups, and 156 between the THSW Decoction and model groups. Thirty-five overlapping metabolites were enriched in cAMP, phospholipase D, and GnRH signaling pathways. Twenty intersection targets linked blood components, metabolites, and hepatic fibrosis. PPI analysis ranked JUN, PTGS2, BCL2, ESR1, and PPARG as the top five targets. A \u201cdrug-component-target-metabolite\u201d network highlighted ferulic acid, p-hydroxycinnamic acid, 3-hydroxy-4-methoxycinnamic acid, ferulaldehyde, and vanillic acid as the top five blood components. Molecular docking and molecular dynamics simulations revealed that 3-hydroxy-4-methoxycinnamic acid binds stably to the core target PPARG, exhibiting a binding free energy of \u221293.68 kJ\/mol. <jats:italic>In vivo<\/jats:italic> validation showed that THSW Decoction upregulated JUN and downregulated ESR1 expression in the liver.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study elucidates THSW Decoction\u2019s key blood components, potential targets, and mechanisms in the treatment of hepatic fibrosis, providing a foundation for further research.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmolb.2025.1614341","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T08:56:06Z","timestamp":1751273766000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Non-targeted metabolomics and network pharmacology of Taohong Siwu Decoction in hepatic fibrosis mouse model using high resolution mass spectrometry"],"prefix":"10.3389","volume":"12","author":[{"given":"Shengsheng","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglan","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongsheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyi","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suping","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhun","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"7873","DOI":"10.3390\/ijms25147873","article-title":"Liver fibrosis: from basic science towards clinical progress, focusing on the central role of hepatic stellate cells","volume":"25","author":"Akkiz","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"48","DOI":"10.5604\/16652681.1226814","article-title":"Management strategies for liver fibrosis","volume":"16","author":"Altamirano-Barrera","year":"2017","journal-title":"Ann. Hepatol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"G977","DOI":"10.1152\/ajpgi.00041.2006","article-title":"Phospholipase D and extracellular signal-regulated kinase in hepatic stellate cells: effects of platelet-derived growth factor and extracellular nucleotides","volume":"291","author":"Benitez-Rajal","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2759","DOI":"10.3390\/cells10102759","article-title":"Cellular and molecular mechanisms underlying liver fibrosis regression","volume":"10","author":"Caligiuri","year":"2021","journal-title":"Cells"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1002\/jcc.20290","article-title":"The Amber biomolecular simulation programs","volume":"26","author":"Case","year":"2005","journal-title":"J. Comput. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e21885","DOI":"10.5812\/hepatmon.21885","article-title":"Estrogen receptor alpha expression and liver fibrosis in chronic hepatitis C virus genotype 1b: a clinicopathological study","volume":"14","author":"Cengiz","year":"2014","journal-title":"Hepat. Mon."},{"key":"B7","doi-asserted-by":"publisher","first-page":"117595","DOI":"10.1016\/j.lfs.2020.117595","article-title":"The in vitro effects of phospholipase D1-mTOR axis in liver fibrogenesis","volume":"251","author":"Chang","year":"2020","journal-title":"Life Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1111\/j.1745-7270.2008.00438.x","article-title":"Epac and PKA: a tale of two intracellular cAMP receptors","volume":"40","author":"Cheng","year":"2008","journal-title":"Acta Biochim. Biophys. Sin. (Shanghai)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"15297","DOI":"10.3390\/ijms232315297","article-title":"Ferulic acid and p-coumaric acid synergistically attenuate non-alcoholic fatty liver disease through HDAC1\/PPARG-mediated free fatty acid uptake","volume":"23","author":"Cui","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"W357","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.3390\/cells10071764","article-title":"Hypoxia, hypoxia-inducible factors and liver fibrosis","volume":"10","author":"Foglia","year":"2021","journal-title":"Cells"},{"key":"B12","doi-asserted-by":"publisher","first-page":"40","DOI":"10.3892\/mmr.2024.13164","article-title":"Liver sinusoidal endothelial cells as potential drivers of liver fibrosis (Review)","volume":"29","author":"Gao","year":"2024","journal-title":"Mol. Med. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S2468-1253(19)30349-8","article-title":"The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"5","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"Genheden","year":"2015","journal-title":"Expert Opin. Drug Discov."},{"key":"B40","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1002\/hep.32163","article-title":"Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases","volume":"75","author":"Gin\u00e8s","year":"2022","journal-title":"Hepatology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2765","DOI":"10.1080\/07391102.2023.2208224","article-title":"System-level protein interaction network analysis and molecular dynamics study reveal interaction of ferulic acid with PTGS2 as a natural radioprotector","volume":"42","author":"Gollapalli","year":"2024","journal-title":"J. Biomol. Struct. Dyn."},{"key":"B16","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1248\/bpb.33.983","article-title":"Hepatoprotective effect of syringic acid and vanillic acid on CCl4-induced liver injury","volume":"33","author":"Itoh","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"B17","doi-asserted-by":"publisher","first-page":"G360","DOI":"10.1152\/ajpgi.00230.2021","article-title":"MAPK p38\/Ulk1 pathway inhibits autophagy and induces IL-1\u03b2 expression in hepatic stellate cells","volume":"322","author":"Jin","year":"2022","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"12435","DOI":"10.1096\/fj.201901046R","article-title":"Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis","volume":"33","author":"Kaftanovskaya","year":"2019","journal-title":"FASEB J."},{"key":"B19","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1053\/j.gastro.2009.09.015","article-title":"Modulation of hepatic fibrosis by c-Jun-N-terminal kinase inhibition","volume":"138","author":"Kluwe","year":"2010","journal-title":"Gastroenterology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.cellimm.2015.01.018","article-title":"Estrogen receptors regulate innate immune cells and signaling pathways","volume":"294","author":"Kovats","year":"2015","journal-title":"Cell. Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1016\/j.ajpath.2017.03.013","article-title":"Knockdown of hepatic gonadotropin-releasing hormone by Vivo-Morpholino decreases liver fibrosis in multidrug resistance gene 2 knockout mice by down-regulation of miR-200b","volume":"187","author":"Kyritsi","year":"2017","journal-title":"Am. J. Pathol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.2147\/DDDT.S310163","article-title":"The agonists of peroxisome proliferator-activated receptor-gamma for liver fibrosis","volume":"15","author":"Li","year":"2021","journal-title":"Drug Des. devel. Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1053\/j.gastro.2020.01.027","article-title":"Identification of lineage-specific transcription factors that prevent activation of hepatic stellate cells and promote fibrosis resolution","volume":"158","author":"Liu","year":"2020","journal-title":"Gastroenterology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"B25","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1055\/s-0040-1708876","article-title":"Hepatic stellate cell-macrophage crosstalk in liver fibrosis and carcinogenesis","volume":"40","author":"Matsuda","year":"2020","journal-title":"Semin. Liver Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1016\/j.biopha.2018.10.005","article-title":"Carvedilol attenuates liver fibrosis by suppressing autophagy and promoting apoptosis in hepatic stellate cells","volume":"108","author":"Meng","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B27","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s13105-020-00777-7","article-title":"Regulation of peroxisome proliferator-activated receptor-gamma activity affects the hepatic stellate cell activation and the progression of NASH via TGF-\u03b21\/Smad signaling pathway","volume":"77","author":"Ni","year":"2021","journal-title":"J. Physiol. Biochem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.jep.2015.01.024","article-title":"Anti-inflammatory activity of a new cyclic peptide, citrusin XI, isolated from the fruits of Citrus unshiu","volume":"163","author":"Noh","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2718","DOI":"10.3390\/molecules26092718","article-title":"Protective role of vanillic acid against diethylnitrosamine- and 1,2-dimethylhydrazine-induced hepatocarcinogenesis in rats","volume":"26","author":"Punvittayagul","year":"2021","journal-title":"Molecules"},{"key":"B30","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3945\/jn.108.097386","article-title":"Ferulaldehyde, a water-soluble degradation product of polyphenols, inhibits the lipopolysaccharide-induced inflammatory response in mice","volume":"139","author":"Radnai","year":"2009","journal-title":"J. Nutr."},{"key":"B31","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1038\/sj.ki.5001626","article-title":"TGF-beta1 induces COX-2 expression and PGE2 synthesis through MAPK and PI3K pathways in human mesangial cells","volume":"70","author":"Rodriguez-Barbero","year":"2006","journal-title":"Kidney Int."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"B33","doi-asserted-by":"publisher","first-page":"875","DOI":"10.3390\/cells9040875","article-title":"Liver fibrosis: mechanistic concepts and therapeutic perspectives","volume":"9","author":"Roehlen","year":"2020","journal-title":"Cells"},{"key":"B34","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1758-2946-6-13","article-title":"TCMSP: a database of systems pharmacology for drug discovery from herbal medicines","volume":"6","author":"Ru","year":"2014","journal-title":"J. Cheminform."},{"key":"B35","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1146\/annurev-pharmtox-010715-103209","article-title":"Nuclear receptors as therapeutic targets in liver disease: are we there yet?","volume":"56","author":"Rudraiah","year":"2016","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1111\/bph.13529","article-title":"Anti-fibrotic actions of relaxin","volume":"174","author":"Samuel","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"108794","DOI":"10.1016\/j.abb.2021.108794","article-title":"Insights into cellular signaling from membrane dynamics","volume":"701","author":"Sarkar","year":"2021","journal-title":"Arch. Biochem. Biophys."},{"key":"B38","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.matbio.2018.04.006","article-title":"Liver fibrosis: direct antifibrotic agents and targeted therapies","author":"Schuppan","year":"2018","journal-title":"Matrix Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1207999","DOI":"10.3389\/fphar.2023.1207999","article-title":"Molecular mechanism and research progress on pharmacology of ferulic acid in liver diseases","volume":"14","author":"Shi","year":"2023","journal-title":"Front. Pharmacol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"980","DOI":"10.2174\/1871520615666150130111120","article-title":"Anticancer agents derived from natural cinnamic acids","volume":"15","author":"Su","year":"2015","journal-title":"Anticancer Agents Med. Chem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e76346","DOI":"10.1371\/journal.pone.0076346","article-title":"TGF-\u03b21 downregulates COX-2 expression leading to decrease of PGE2 production in human lung cancer A549 cells, which is involved in fibrotic response to TGF-\u03b21","volume":"8","author":"Takai","year":"2013","journal-title":"PLoS One"},{"key":"B43","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1002\/hep4.1203","article-title":"Nuclear receptors and liver disease: summary of the 2017 basic research symposium","volume":"2","author":"Tran","year":"2018","journal-title":"Hepatol. Commun."},{"key":"B44","doi-asserted-by":"publisher","first-page":"109204","DOI":"10.1016\/j.jnutbio.2022.109204","article-title":"Attenuation of hepatic fibrosis by p-coumaric acid via modulation of NLRP3 inflammasome activation in C57BL\/6 mice","volume":"112","author":"Truong","year":"2023","journal-title":"J. Nutr. Biochem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.cellsig.2018.06.005","article-title":"Role of cAMP and phosphodiesterase signaling in liver health and disease","volume":"49","author":"Wahlang","year":"2018","journal-title":"Cell. Signal."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and testing of a general amber force field","volume":"25","author":"Wang","year":"2004","journal-title":"J. Comput. Chem."},{"key":"B47","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1007\/s11655-018-3007-1","article-title":"Angiogenesis and hepatic fibrosis: western and Chinese medicine therapies on the road","volume":"24","author":"Wang","year":"2018","journal-title":"Chin. J. Integr. Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.2147\/DDDT.S194787","article-title":"Salvianolic acid A attenuates CCl4-induced liver fibrosis by regulating the PI3K\/AKT\/mTOR, Bcl-2\/Bax and caspase-3\/cleaved caspase-3 signaling pathways","volume":"13","author":"Wang","year":"2019","journal-title":"Drug Des. devel. Ther."},{"key":"B49","doi-asserted-by":"publisher","first-page":"806","DOI":"10.21037\/apm-21-3286","article-title":"Role of the PI3K\/Akt signaling pathway in liver ischemia reperfusion injury: a narrative review","volume":"11","author":"Wang M.","year":"2022","journal-title":"Ann. Palliat. Med."},{"key":"B50","doi-asserted-by":"publisher","first-page":"633","DOI":"10.3390\/toxins14090633","article-title":"Combined hepatotoxicity and toxicity mechanism of intermedine and lycopsamine","volume":"14","author":"Wang Z.","year":"2022","journal-title":"Toxins (Basel)"},{"key":"B51","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1002\/hep.29689","article-title":"New insights into the role and mechanism of c-Jun-N-terminal kinase signaling in the pathobiology of liver diseases","volume":"67","author":"Win","year":"2018","journal-title":"Hepatology"},{"key":"B52","doi-asserted-by":"publisher","first-page":"118456","DOI":"10.1016\/j.jep.2024.118456","article-title":"Tao-Hong-Si-Wu-Tang improves thioacetamide-induced liver fibrosis by reversing ACSL4-mediated lipid accumulation and promoting mitophagy","volume":"333","author":"Wu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.jep.2016.01.030","article-title":"The effects of Tao-Hong-Si-Wu on hepatic necroinflammatory activity and fibrosis in a murine model of chronic liver disease","volume":"180","author":"Xi","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"120025","DOI":"10.1016\/j.jep.2025.120025","article-title":"Taohong Siwu Decoction modulates glutathione metabolism to suppress hepatocyte ferroptosis and demonstrates anti-fibrotic effects in the liver","volume":"350","author":"Xiao","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"18799","DOI":"10.1038\/s41598-023-46132-w","article-title":"Single-cell RNA sequencing revealed potential targets for immunotherapy studies in hepatocellular carcinoma","volume":"13","author":"Xie","year":"2023","journal-title":"Sci. Rep."},{"key":"B56","doi-asserted-by":"publisher","first-page":"250","DOI":"10.3748\/wjg.v10.i2.250","article-title":"Effects of estradiol on liver estrogen receptor-alpha and its mRNA expression in hepatic fibrosis in rats","volume":"10","author":"Xu","year":"2004","journal-title":"World J. Gastroenterol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"939631","DOI":"10.3389\/fimmu.2022.939631","article-title":"The hepatoprotective and hepatotoxic roles of sex and sex-related hormones","volume":"13","author":"Xu","year":"2022","journal-title":"Front. Immunol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.cca.2020.03.024","article-title":"COX-2 in liver fibrosis","volume":"506","author":"Yang","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"B59","doi-asserted-by":"publisher","first-page":"2689","DOI":"10.1016\/j.bmc.2009.02.057","article-title":"Phenolic compounds with radical scavenging and cyclooxygenase-2 (COX-2) inhibitory activities from Dioscorea opposita","volume":"17","author":"Yang","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"B60","doi-asserted-by":"publisher","first-page":"101267","DOI":"10.1016\/j.plipres.2023.101267","article-title":"Phosphatidic acid signaling and function in nuclei","volume":"93","author":"Yao","year":"2024","journal-title":"Prog. Lipid Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1055\/s-0036-1571295","article-title":"Antifibrotic therapies: where are we now?","volume":"36","author":"Yoon","year":"2016","journal-title":"Semin. Liver Dis."},{"key":"B62","doi-asserted-by":"publisher","first-page":"256","DOI":"10.3892\/ijmm.2020.4778","article-title":"TGF-\u03b21-induced autophagy activates hepatic stellate cells via the ERK and JNK signaling pathways","volume":"47","author":"Zhang","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"B63","doi-asserted-by":"publisher","first-page":"e34410","DOI":"10.1016\/j.heliyon.2024.e34410","article-title":"Identification of novel NLRP3 inhibitors as therapeutic options for epilepsy by machine learning-based virtual screening, molecular docking and biomolecular simulation studies","volume":"10","author":"Zulfat","year":"2024","journal-title":"Heliyon"}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2025.1614341\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T08:56:07Z","timestamp":1751273767000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2025.1614341\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":63,"alternative-id":["10.3389\/fmolb.2025.1614341"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2025.1614341","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]},"article-number":"1614341"}}