{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:03:51Z","timestamp":1789625031362,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"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>Background<\/jats:title>\n                    <jats:p>\n                      Hepatic fibrosis represents a critical pathological stage in the progression of chronic liver diseases, yet clinically effective and low-toxicity therapeutic options remain limited.\n                      <jats:italic>Taraxacum mongolicum<\/jats:italic>\n                      and Astragalus form a classic hepatoprotective herbal pair, and their derived polysaccharides-\n                      <jats:italic>Taraxacum mongolicum<\/jats:italic>\n                      polysaccharides (TMP) and Astragalus polysaccharides (APS)-both exhibit hepatoprotective activities. This study aimed to investigate the ameliorative effects of TMP combined with APS on CCl\n                      <jats:sub>4<\/jats:sub>\n                      -induced hepatic fibrosis in mice and the gut-liver axis-associated changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Mice were randomly assigned to the blank control, model, silybin, Lizhu Changle (live Bifidobacterium adolescentis capsules), TMP monotherapy, APS monotherapy, and combination groups. Following the establishment of fibrosis by CCl\n                      <jats:sub>4<\/jats:sub>\n                      , a 4-week intervention was administered. Serum liver function parameters and fibrosis markers were measured, and hepatic histopathological changes were observed. Intestinal function was comprehensively evaluated. Gut microbiota composition was analyzed using 16S rRNA gene sequencing, and fecal short-chain fatty acid (SCFA) levels were quantified by high-performance liquid chromatography (HPLC). The protein expression of the hepatic TLR4\/MyD88\/NF-\u03baB pathway was further assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with TMP or APS alone, the combination significantly improved multiple fibrosis-related, inflammatory, intestinal barrier, microbial diversity, and SCFA-related indices, although significant superiority was not observed for PC III and TNF-\u03b1. The combination also more strongly suppressed hepatic TLR4\/MyD88\/NF-\u03baB pathway expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TMP combined with APS exerts enhanced anti-hepatic fibrosis effects compared with either monotherapy. These effects are associated with changes in gut microbiota composition, elevated fecal short-chain fatty acid levels, reduced expression of hepatic TLR4\/MyD88\/NF-\u03baB pathway-related molecules. These findings provide an experimental basis for further investigation of this herbal pair.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1904671","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:33:20Z","timestamp":1789623200000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Taraxacum mongolicum and Astragalus polysaccharides attenuate CCl4-induced hepatic fibrosis through modulation of the TLR4\/MyD88\/NF-\u03baB signaling pathway and gut microbiota composition"],"prefix":"10.3389","volume":"17","author":[{"given":"Yingjie","family":"Ma","sequence":"first","affiliation":[{"name":"College of Pharmacy, Jiamusi University","place":["Jiamusi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoxing","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jiamusi University","place":["Jiamusi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jiamusi University","place":["Jiamusi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqing","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Jiamusi University","place":["Jiamusi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jiamusi University","place":["Jiamusi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baisong","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jiamusi University","place":["Jiamusi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenda","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jiamusi University","place":["Jiamusi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Shen","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jiamusi University","place":["Jiamusi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Jiamusi University","place":["Jiamusi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jiamusi University","place":["Jiamusi, China"]},{"name":"College of Basic Medicine, Jiamusi University","place":["Jiamusi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1364023","DOI":"10.3389\/fphar.2024.1364023","article-title":"Transcriptomic analysis reveals pharmacological mechanisms mediating efficacy of Yangyinghuoxue Decoction in CCl4-induced hepatic fibrosis in rats","volume":"15","author":"Bai","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1016\/j.ijbiomac.2019.08.161","article-title":"Optimization of extraction of polysaccharide from dandelion root by response surface methodology: structural characterization and antioxidant activity","volume":"140","author":"Cai","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"124422","DOI":"10.1016\/j.ijbiomac.2023.124422","article-title":"Effects of dietary dandelion (Taraxacum mongolicum Hand.-Mazz.) polysaccharides on the performance and gut microbiota of laying hens","volume":"240","author":"Cao","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3390\/molecules29010127","article-title":"Research progress regarding the effect and mechanism of dietary polyphenols in liver fibrosis","volume":"29","author":"Chang","year":"2023","journal-title":"Molecules"},{"key":"B5","doi-asserted-by":"publisher","first-page":"479","DOI":"10.5009\/gnl240539","article-title":"Gut-liver axis: the role of intestinal microbiota and their metabolites in the progression of metabolic dysfunction-associated steatotic liver disease","volume":"19","author":"Cui","year":"2025","journal-title":"Gut Liver"},{"key":"B6","doi-asserted-by":"publisher","first-page":"157830","DOI":"10.1016\/j.phymed.2026.157830","article-title":"Qing Hua Yu Du formula ameliorates alcoholic hepatic fibrosis by regulating MAPK\/TLR4-MyD88 inflammatory pathways, restoring hepatic metabolism and modulating gut microbiota","volume":"152","author":"Ding","year":"2026","journal-title":"Phytomedicine"},{"key":"B7","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.lfs.2017.11.047","article-title":"Lycium barbarum polysaccharides improve CCl(4)-induced liver fibrosis, inflammatory response and TLRs\/NF-kB signaling pathway expression in wistar rats","volume":"192","author":"Gan","year":"2018","journal-title":"Life Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.rvsc.2017.05.002","article-title":"Amelioration of CCl(4)-induced liver injury in rats by selenizing Astragalus polysaccharides: role of proinflammatory cytokines, oxidative stress and hepatic stellate cells","volume":"114","author":"Hamid","year":"2017","journal-title":"Res. Vet. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"119117","DOI":"10.1016\/j.jep.2024.119117","article-title":"Angelica sinensis polysaccharide could alleviate the gastrointestinal damage in alcoholic fatty liver disease mice: regulation of alcohol metabolism and enhancement of short-chain fatty acids utilization","volume":"338","author":"He","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"157798","DOI":"10.1016\/j.phymed.2026.157798","article-title":"Baoganning decoction mitigates liver fibrosis via regulating IDO1-mediated macrophage efferocytosis","volume":"151","author":"Kuang","year":"2026","journal-title":"Phytomedicine"},{"key":"B11","doi-asserted-by":"publisher","first-page":"112442","DOI":"10.1016\/j.jep.2019.112442","article-title":"Advances in anti hepatic fibrotic therapy with Traditional Chinese medicine herbal formula","volume":"251","author":"Li","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"619","DOI":"10.2147\/dddt.S98740","article-title":"Protective effect of fucoidan from Fucus vesiculosus on liver fibrosis via the TGF-\u03b21\/Smad pathway-mediated inhibition of extracellular matrix and autophagy","volume":"10","author":"Li","year":"2016","journal-title":"Drug Des. Devel Ther."},{"key":"B13","doi-asserted-by":"publisher","first-page":"962525","DOI":"10.3389\/fphar.2022.962525","article-title":"Traditional Chinese medicine: an important source for discovering candidate agents against hepatic fibrosis","volume":"13","author":"Li","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1347120","DOI":"10.3389\/fphar.2024.1347120","article-title":"Gut microbes combined with metabolomics reveal the protective effects of Qijia Rougan decoction against CCl(4)-induced hepatic fibrosis","volume":"15","author":"Li","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.3390\/ijms25031429","article-title":"Modulation of acute intestinal inflammation by dandelion polysaccharides: an In-Depth analysis of antioxidative, anti-inflammatory effects and gut microbiota regulation","volume":"25","author":"Li","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"116915","DOI":"10.1016\/j.celrep.2025.116915","article-title":"Scar-associated endothelial-stellate cellular crosstalk drives fibrosis resolution in MASH","volume":"45","author":"Li","year":"2026","journal-title":"Cell Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"747","DOI":"10.3892\/mmr.2012.1248","article-title":"Protective effect of Cordyceps polysaccharide on hydrogen peroxide-induced mitochondrial dysfunction in HL-7702 cells","volume":"7","author":"Liu","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"B18","doi-asserted-by":"publisher","first-page":"582","DOI":"10.3389\/fphar.2020.00582","article-title":"Isochlorogenic acid A attenuates the progression of liver fibrosis through regulating HMGB1\/TLR4\/NF-\u03baB signaling pathway","volume":"11","author":"Liu","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1018557","DOI":"10.3389\/fendo.2022.1018557","article-title":"Seabuckthorn polysaccharide combined with astragalus polysaccharide ameliorate alcoholic fatty liver by regulating intestinal flora","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2715","DOI":"10.2147\/dddt.S467480","article-title":"Advances in research on the effectiveness and mechanism of active ingredients from traditional Chinese medicine in regulating hepatic stellate cells autophagy against hepatic fibrosis","volume":"18","author":"Liu","year":"2024","journal-title":"Drug Des. Devel Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1186\/s13046-025-03608-z","article-title":"Colon-targeted astragalus polysaccharide nanoparticles prevent NAFLD-driven hepatocarcinogenesis via microbiota remodeling and NF-\u03baB inhibition","volume":"44","author":"Liu","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e10562","DOI":"10.1002\/advs.202510562","article-title":"p16(Ink4a)-Positive hepatocytes drive liver fibrosis through activation of LIFR family pathway","volume":"13","author":"Nishikawa","year":"2026","journal-title":"Adv. Sci. (Weinh)"},{"key":"B23","doi-asserted-by":"publisher","first-page":"19323","DOI":"10.1038\/s41598-024-70253-5","article-title":"Lactucin reverses liver fibrosis by inhibiting TGF-\u03b21\/STAT3 signaling pathway and regulating short-chain fatty acids metabolism","volume":"14","author":"Qin","year":"2024","journal-title":"Sci. Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0303924","DOI":"10.1128\/spectrum.03039-24","article-title":"Synergistic gut microbiome-mediated degradation of Astragalus membranaceus polysaccharides and Codonopsis pilosula polysaccharides into butyric acid: a metatranscriptomic analysis","volume":"13","author":"Rong","year":"2025","journal-title":"Microbiol. Spectr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1243834","DOI":"10.3389\/fimmu.2023.1243834","article-title":"Astragalus improves intestinal barrier function and immunity by acting on intestinal microbiota to treat T2DM: a research review","volume":"14","author":"Su","year":"2023","journal-title":"Front. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1407991","DOI":"10.3389\/fmicb.2024.1407991","article-title":"Potential mechanisms of traditional Chinese medicine in the treatment of liver cirrhosis: a focus on gut microbiota","volume":"15","author":"Sun","year":"2024","journal-title":"Front. Microbiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s12951-025-03940-8","article-title":"Targeted blockade of extracellular vesicles-mediated profibrotic vicious circle using EVs-based dual-drug delivery system to prevent liver fibrosis","volume":"24","author":"Sun","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.12659\/msm.909320","article-title":"A polysaccharide from amusium pleuronectes combined with praziquantel treatment ameliorates hepatic fibrosis in Schistosoma Japonicum-infected mice","volume":"24","author":"Tang","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"B29","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1080\/13880209.2018.1479868","article-title":"Effects of garlic polysaccharide on alcoholic liver fibrosis and intestinal microflora in mice","volume":"56","author":"Wang","year":"2018","journal-title":"Pharm. Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"114862","DOI":"10.1016\/j.biopha.2023.114862","article-title":"Astragalus polysaccharide ameliorated complex factor-induced chronic fatigue syndrome by modulating the gut microbiota and metabolites in mice","volume":"163","author":"Wei","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B31","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1007\/s12072-023-10534-9","article-title":"Global burden of cirrhosis and liver cancer due to alcohol: the past, present, and the future","volume":"17","author":"Xie","year":"2023","journal-title":"Hepatol. Int."},{"key":"B32","doi-asserted-by":"publisher","first-page":"351","DOI":"10.3390\/metabo14070351","article-title":"Integrated microbiome-metabolomics analysis reveals the potential mechanism of dandelion root polysaccharides to ameliorate ulcerative colitis","volume":"14","author":"Yan","year":"2024","journal-title":"Metabolites"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e410","DOI":"10.1002\/ctm2.410","article-title":"Rebalancing TGF-\u03b2\/Smad7 signaling via compound kushen injection in hepatic stellate cells protects against liver fibrosis and hepatocarcinogenesis","volume":"11","author":"Yang","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1097\/01.shk.0000225404.51320.82","article-title":"HMGB1 signals through toll-like receptor (TLR) 4 and TLR2","volume":"26","author":"Yu","year":"2006","journal-title":"Shock"},{"key":"B35","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/j.ijbiomac.2019.09.002","article-title":"Protective effects of polysaccharides on hepatic injury: a review","volume":"141","author":"Yuan","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.jtcme.2024.05.007","article-title":"Astragalus mongholicus polysaccharides alleviate insulin resistance through modulation of PI3K\/AKT, TLR4\/NF-kB signaling pathway and microbiota in rats with type 2 diabetes mellitus","volume":"15","author":"Yuan","year":"2025","journal-title":"J. Tradit. Complement. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jep.2015.12.053","article-title":"Hepatoprotective effects of Dicliptera chinensis polysaccharides on dimethylnitrosamine-induced hepatic fibrosis rats and its underlying mechanism","volume":"179","author":"Zhang","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e250293","DOI":"10.1530\/joe-25-0293","article-title":"Iron homeostasis links the association between alcohol consumption and liver steatosis\/fibrosis: a multi-cohort analysis","volume":"268","author":"Zhang","year":"2026","journal-title":"J. Endocrinol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.jphs.2022.10.001","article-title":"Aronia melanocarpa polysaccharide ameliorates liver fibrosis through TGF-\u03b21-mediated the activation of PI3K\/AKT pathway and modulating gut microbiota","volume":"150","author":"Zhao","year":"2022","journal-title":"J. Pharmacol. Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1186\/s12876-014-0224-8","article-title":"The influence of astragalus polysaccharide and \u03b2-elemene on LX-2 cell growth, apoptosis and activation","volume":"14","author":"Zheng","year":"2014","journal-title":"BMC Gastroenterol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1142\/s0192415x24500666","article-title":"Research progress of Chinese medicine in the regulation of liver fibrosis-related signaling pathways","volume":"52","author":"Zheng","year":"2024","journal-title":"Am. J. Chin. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2688","DOI":"10.3390\/foods10112688","article-title":"Astragalus polysaccharides and saponins alleviate liver injury and regulate gut microbiota in alcohol liver disease mice","volume":"10","author":"Zhou","year":"2021","journal-title":"Foods"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1273031","DOI":"10.3389\/fcimb.2023.1273031","article-title":"Convergent application of traditional Chinese medicine and gut microbiota in ameliorate of cirrhosis: a data mining and Mendelian randomization study","volume":"13","author":"Zhou","year":"2023","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"4120","DOI":"10.3390\/nu15194120","article-title":"Dandelion polysaccharides ameliorate high-fat-diet-induced atherosclerosis in mice through antioxidant and anti-inflammatory capabilities","volume":"15","author":"Zhou","year":"2023","journal-title":"Nutrients"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1904671\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:33:21Z","timestamp":1789623201000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1904671\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":44,"alternative-id":["10.3389\/fphar.2026.1904671"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1904671","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"article-number":"1904671"}}