{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T06:18:20Z","timestamp":1783491500154,"version":"3.55.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Liver fibrosis is a critical pathological process to irreversible cirrhosis. The valued\n                      <jats:italic>Ophiocordyceps sinensis<\/jats:italic>\n                      (Berk.) G.H. Sung, J.M. Sung, Hywel-Jones and Spatafora (Ophiocordycipitaceae, Hypocreales) fungus exhibits remarkable hepatoprotective effects, especially anti-inflammation. However, detailed metabolites with anti-inflammation activity need to be explored from this fungus. This study investigates the anti-liver fibrosis effect of cerevisterol extracted from\n                      <jats:italic>O. sinensis<\/jats:italic>\n                      fruiting bodies on TGF-\u03b21-induced LX-2 cells (a human hepatic stellate cell line) and the underlying potential mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The metabolites were extracted and purified by petroleum ether, ethanol reflux extraction and chromatographic separation technology. Their structures were identified based on extensive NMR and MS data. TGF-\u03b21-induced LX-2 cells were employed to study the anti-inflammation activity of the isolated cerevisterol. The mRNA expression of\n                      <jats:italic>Smad3, Smad4<\/jats:italic>\n                      , and\n                      <jats:italic>Collagen I<\/jats:italic>\n                      in the cells was verified by qRT-PCR and Smad3 and Smad4 proteins by Western blot.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cerevisterol, adenosine, uridine, ergosterol, 2-piperidone, L-tryptophan and (24S)-ergost-7(8)-en-3\u03b2,5\u03b1,6\u03b2-triol were obtained. In the TGF-\u03b21-induced fibrosis model, cerevisterol (10 \u03bcM) and a commercial anti-liver fibrosis drug containing Chinese cordyceps (75 ng\/mL) as positive control significantly suppressed cell proliferation at 72 and 96 hours. qRT-PCR analysis demonstrated that cerevisterol downregulated mRNA expression of Smad3, Smad4, and Collagen I. Western blot results confirmed reduced protein levels of Smad3 and Smad4 in the cerevisterol-treated cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Cerevisterol from\n                      <jats:italic>O. sinensis<\/jats:italic>\n                      fungus exerts anti-liver fibrosis effects by inhibiting hepatic stellate cell activation and proliferation, and by downregulating TGF-\u03b2\/Smad3 signaling pathway, thereby reducing excessive extracellular matrix-related gene and protein expression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1825109","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:54:47Z","timestamp":1783490087000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cerevisterol from Ophiocordyceps sinensis fruiting bodies against liver fibrosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Minting","family":"Yang","sequence":"first","affiliation":[{"name":"Qinghai Normal University","place":["Xining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Sun","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richou","family":"Han","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huichun","family":"Xie","sequence":"additional","affiliation":[{"name":"Qinghai Normal University","place":["Xining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Cao","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.carbpol.2018.05.081","article-title":"Rheological, structural and functional properties of high-pressure treated quinoa starch in dispersions","volume":"197","author":"Ahmed","year":"2018","journal-title":"Carbohyd. Polym."},{"key":"B2","doi-asserted-by":"publisher","first-page":"103356","DOI":"10.1016\/j.algal.2023.103356","article-title":"Optimization of ultrasonic-assisted extraction of polysaccharides from ulva rigida and evaluation of their antioxidant activity","volume":"77","author":"Akbal","year":"2024","journal-title":"Algal Res."},{"key":"B3","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":"Akk\u0131z","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/biom10020199Phytomedicine.75(153189","article-title":"Cerevisterol alleviates inflammation via suppression of MAPK\/NF-\u03baB\/AP-1 and activation of the Nrf2\/HO-1 signaling cascade","volume":"10","author":"Alam","year":"2020","journal-title":"Biomolecules"},{"key":"B5","doi-asserted-by":"publisher","first-page":"G245","DOI":"10.1152\/ajpgi.2000.279.2.G245","article-title":"Metalloproteinases and their inhibitors in liver fibrosis","volume":"279","author":"Arthur","year":"2000","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1111\/j.1524-4725.2012.02411.x","article-title":"Acne vulgaris: the role of oxidative stress and the potential therapeutic value of local and systemic antioxidants","volume":"11","author":"Bowe","year":"2012","journal-title":"J. Drugs Dermatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/jcm12030979","article-title":"Efficacy of submicron dispersible free phytosterols on non-alcoholic fatty liver disease: a pilot study","volume":"12","author":"Bra\u00f1es","year":"2023","journal-title":"Clin. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1615\/intjmedmushrooms.v17.i11.110","article-title":"Fruiting body production of the medicinal Chinese caterpillar mushroom, Ophiocordyceps sinensis (Ascomycetes), in artificial medium","volume":"17","author":"Cao","year":"2015","journal-title":"Int. J. Med. Mushrooms."},{"key":"B9","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.ijbiomac.2021.09.087","article-title":"Synthesis and evaluation of Grateloupia livida polysaccharides-functionalized selenium nanoparticles","volume":"191","author":"Cao","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"B10","volume-title":"Use of Fufang Biejia Ruangan Pian in Treating Chronic Hepatitis B Liver Fibrosis","author":"Chen","year":"2000"},{"key":"B11","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.jff.2012.11.013","article-title":"Properties of cordyceps sinensis: a review","volume":"5","author":"Chen","year":"2013","journal-title":"J. Funct. Foods."},{"key":"B12","doi-asserted-by":"publisher","first-page":"114678","DOI":"10.1016\/j.jpba.2022.114678","article-title":"Development of a rapid and sensitive LC-MS\/MS assay for the quantification of commonly abused drugs in Asia in a micro-segment of a single hair using microwave-assisted extraction and dansyl chloride derivatization","volume":"213","author":"Chen","year":"2022","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B13","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1142\/S0192415X14500281","article-title":"Cordyceps sinensis prevents apoptosis in mouse liver with d-galactosa mine\/lipopolysaccharide-induced fulminant hepatic failure","volume":"42","author":"Cheng","year":"2014","journal-title":"Am. J. Chin. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.phymed.2015.05.001","article-title":"Anti-hepatitis B virus activities of friedelolactones from Viola diffusa Ging","volume":"22","author":"Dai","year":"2015","journal-title":"Phytomedicine"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3038","DOI":"10.1038\/s41467-025-57616-w","article-title":"Targeting senescent hepatocytes for treatment of metabolic dysfunction-associated steatotic liver disease and multi-organ dysfunction","volume":"16","author":"Du","year":"2025","journal-title":"Nat. Commun."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e62987","DOI":"10.3791\/62987","article-title":"Brain organoid generation from induced pluripotent stem cells in home-made mini bioreactors","volume":"178","author":"Eremeev","year":"2021","journal-title":"J. Vis. Exp."},{"key":"B17","doi-asserted-by":"publisher","first-page":"461234","DOI":"10.1016\/j.chroma.2020.461234","article-title":"Simultaneous determination of nine atmospheric amines and six inorganic ions by non-suppressed ion chromatography using acetonitrile and 18-crown-6 as eluent additive","volume":"1624","author":"Feng","year":"2020","journal-title":"J. Chromatogr. A"},{"key":"B18","doi-asserted-by":"publisher","first-page":"671152","DOI":"10.3389\/fphar.2021.671152","article-title":"The novel Chinese medicine JY5 formula alleviates hepatic fibrosis by inhibiting the notch signaling pathway","volume":"15","author":"Fu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1002\/hlca.200790116","article-title":"New steryl esters of fatty acids from the mangrove fungus Aspergillus awamori","volume":"90","author":"Gao","year":"2007","journal-title":"HCA"},{"key":"B20","doi-asserted-by":"publisher","first-page":"3107","DOI":"10.1091\/mbc.e05-02-0103","article-title":"Dynein light chain 1 regulates dynamin-mediated F-actin assembly during sperm individualization in drosophila","volume":"16","author":"Ghosh-Roy","year":"2025","journal-title":"Mol. Biol. Cell."},{"key":"B21","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1186\/s12967-024-05411-4","article-title":"TGF-\u03b2 signaling: critical nexus of fibrogenesis and cancer","volume":"22","author":"Giarratana","year":"2024","journal-title":"J. Transl. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/molecules28237896","article-title":"Target screen of anti-hyperuricemia compounds from cortex fraxini in vivo based on ABCG2 and bioaffinity ultrafiltration mass spectrometry","volume":"28","author":"Huang","year":"2023","journal-title":"Molecules"},{"key":"B23","doi-asserted-by":"publisher","first-page":"0069","DOI":"10.1055\/s-0034-1379693","article-title":"Synthesis of 1,2-amino alcohols via asymmetric hydrogenation","volume":"11","author":"Lautens","year":"2015","journal-title":"Synfacts"},{"key":"B24","doi-asserted-by":"publisher","first-page":"174856","DOI":"10.1016\/j.ejphar.2022.174856","article-title":"Piperazine ferulate protects against cardiac ischemia\/reperfusion injury in rat via the suppression of NLRP3 inflammasome activation and pyroptosis","volume":"920","author":"Lei","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.coph.2019.09.006","article-title":"New and emerging anti-fibrotic therapeutics entering or already in clinical trials in chronic liver diseases","volume":"49","author":"Lemoinne","year":"2019","journal-title":"COPHAR"},{"key":"B26","doi-asserted-by":"publisher","first-page":"477","DOI":"10.3321\/j.issn:1001-2494.2003.07.007","article-title":"Chemical constituents from Cordyceps sinensis (berk.) sacc","volume":"26","author":"Li","year":"2003","journal-title":"Chin. Pharm. J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12887-024-05009-1","article-title":"Effect of dietary antioxidant quality score on tobacco smoke exposure and asthma in children and adolescents: a cross-sectional study from the NHANES database","volume":"24","author":"Lin","year":"2024","journal-title":"BMC Pediatr."},{"key":"B28","doi-asserted-by":"publisher","first-page":"529","DOI":"10.3748\/wjg.v9.i3.529","article-title":"Inhibitive effect of Cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism","volume":"9","author":"Liu","year":"2003","journal-title":"World J. Gastroenterol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"114130","DOI":"10.1016\/j.jep.2021.114130","article-title":"Immunostimulatory effects of the intracellular polysaccharides isolated from liquid culture of Ophiocordyceps sinensis (Ascomycetes) on RAW264.7 cells via the MAPK and PI3K\/Akt signaling pathways","volume":"275","author":"Liu","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13020-024-00896-z","article-title":"A novel network pharmacology strategy to decode mechanism of wuling powder in treating liver cirrhosis","volume":"19","author":"Liu","year":"2024","journal-title":"Chin. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jep.2021.114215","article-title":"Discovery of the signal pathways and major bioactive compounds responsible for the anti-hypoxia effect of Chinese cordyceps","volume":"277","author":"Long","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"114564","DOI":"10.1016\/j.phytochem.2025.114564","article-title":"Astraeusols A-E: lanostane-type triterpenes from the wild edible mushroom Astraeus asiaticus","volume":"238","author":"Maliwong","year":"2025","journal-title":"Phytochemistry"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1093\/emboj\/19.8.1745","article-title":"Transcriptional control by the TGF-beta\/Smad signaling system","volume":"19","author":"Massagu\u00e9","year":"2020","journal-title":"EMBO J."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jchromb.2008.02.021","article-title":"Size-exclusion chromatography with evaporative light scattering detection: method for determination of polydimethylsiloxanes. I. Testing dependence of molecular weight of polydimethylsiloxanes and injected mass upon the detector signal","volume":"865","author":"Mojsiewicz-Pie\u0144kowska","year":"2008","journal-title":"J. Chromatogr. B"},{"key":"B35","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods."},{"key":"B36","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1177\/1535370213480741","article-title":"Anti-fibrotic effects of Ophiocordyceps sinensis polysaccharide: inhibiting HSC activation, TGF-\u03b21\/Smad signalling, MMPs and TIMPs","volume":"38","author":"Peng","year":"2013","journal-title":"Exp. Biol. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1007\/s11033-014-3031-y","article-title":"Cultured mycelium Cordyceps sinensis protects liver sinusoidal endothelial cells in acute liver injured mice","volume":"41","author":"Peng","year":"","journal-title":"Mol. Biol. Rep."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/537234","article-title":"Ergosterol is the active compound of cultured mycelium Cordyceps sinensis on antiliver fibrosis","volume":"2014","author":"Peng","year":"","journal-title":"eCAM"},{"key":"B39","doi-asserted-by":"publisher","first-page":"153892","DOI":"10.1016\/j.jplph.2022.153892","article-title":"Mitochondrial alternative oxidase enhanced ABA-mediated drought tolerance in Solanum lycopersicum","volume":"280","author":"Qiao","year":"2023","journal-title":"J. Plant Physiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1055\/s-0029-1240897","article-title":"A new cytotoxic trichothecene macrolide from the endophyte Myrothecium roridum","volume":"76","author":"Shen","year":"2010","journal-title":"Planta. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1016\/j.ijbiomac.2017.08.065","article-title":"Optimized extraction and characterization of pectin from jackfruit (Artocarpus integer) wastes using response surface methodology","volume":"106","author":"Sundarraj","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","author":"Tsuchida","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41429-018-0135-y","article-title":"Antimicrobial anthraquinones from cultures of the ant pathogenic fungus Cordyceps morakotii BCC 56811","volume":"72","author":"Wang","year":"2019","journal-title":"J. Antibiot."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e0277873","DOI":"10.1371\/journal.pone.0277873[45","article-title":"Poria cocos compounds targeting neuropeptide Y1 receptor (Y1R) for weight management: a computational ligand- and structure-based study with molecular dynamics simulations identified beta-amyrin acetate as a putative Y1R inhibitor","volume":"18","author":"Wong","year":"2023","journal-title":"PLoS ONE"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1002\/tox.22402","article-title":"Preventive effects of Ophiocordyceps sinensis mycelium on the liver fibrosis induced by thioacetamide","volume":"32","author":"Wu","year":"2017","journal-title":"Environ. Toxicol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1369\/0022155415627681","article-title":"TGF-\u03b2\/SMAD pathway and its regulation in hepatic fibrosis","volume":"64","author":"Xu","year":"2016","journal-title":"J. Histochem. Cytochem."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2134","DOI":"10.1186\/s40104-025-01228-3","article-title":"Integrated transcriptomics and metabolomics reveal multi-target mechanisms of tannins against Clostridium perfringens and necrotic enteritis","volume":"16","author":"Xu","year":"2025","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"282","DOI":"10.21037\/atm-22-762","article-title":"Exploring the mechanisms of action of Cordyceps sinensis for the treatment of depression using network pharmacology and molecular docking","volume":"10","author":"Zhang","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"115567","DOI":"10.1016\/j.jep.2022.115567","article-title":"An optimized herbal combination for the treatment of liver fibrosis: hub genes, bioactive ingredients, and molecular mechanisms","volume":"297","author":"Zhao","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"124689","DOI":"10.1016\/j.ijbiomac.2023.124689","article-title":"Angelica sinensis aboveground part polysaccharide and its metabolite 5-MT ameliorate colitis via modulating gut microbiota and TLR4\/MyD88\/NF-\u03baB pathway","volume":"242","author":"Zou","year":"2023","journal-title":"Int. J. Biol. Macromol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1825109\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:54:49Z","timestamp":1783490089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1825109\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":50,"alternative-id":["10.3389\/fphar.2026.1825109"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1825109","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"article-number":"1825109"}}