{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T16:07:09Z","timestamp":1782490029866,"version":"3.54.5"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"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><jats:title>Introduction<\/jats:title><jats:p>Metabolic-associated fatty liver disease (MAFLD) is a liver disease syndrome. The total flavonoids of Dracocephalum moldavica L. (D. moldavica), the main active components of D. moldavica, have been demonstrated not only to have anti-inflammatory and antioxidant effects but also to regulate gut microbiota. However, the mechanism by which it improves MAFLD is unclear. So we want to investigate how the total flavonoids of D. moldavica alleviate high-fat diet (HFD)-induced MAFLD in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Firstly, MAFLD rat models were established by feeding with HFD, while the total flavonoids of D. moldavica were administered via gavage. Then, the experiments analyzed the changes of gut microbiota by the 16S rRNA sequencing and detected intestinal barrier permeability and liver inflammation to explore the mechanism of the total flavonoids of D. moldavica in the prevention and treatment of MAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that the total flavonoids of D. moldavica reduced systemic inflammation and could alleviate serum and liver lipid metabolism disorders in MAFLD rats. The results of the 16S rRNA sequencing demonstrated that the total flavonoids of D. moldavica increased the abundance and diversity of gut microbiota. Furthermore, the total flavonoids of D. moldavica have been demonstrated to enhance the intestinal mucosal barrier function, reduce LPS translocation, and inhibit the activation of hepatic TLR4\/MyD88\/NF-\u03baB pathway. This could effectively ameliorate the hepatic lesions in MAFLD rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The aforementioned outcomes indicate that the total flavonoids ofD moldavica may potentially alleviate MAFLD by modulating gut microbiota, intestinal mucosal barrier and hepatic inflammation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1549515","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T05:31:11Z","timestamp":1747287071000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Effect of the total flavonoids of Dracocephalum moldavica L. on metabolic associated fatty liver disease in rats"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaoyu","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"941","DOI":"10.3390\/plants11070941","article-title":"Chemical composition, antio xidant, and antimicrobial activity of Dracocephalum moldavica L. Essential oil and hydrolate","volume":"11","author":"A\u0107imovi\u0107","year":"2022","journal-title":"Plants (Basel)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"550","DOI":"10.3390\/biomedicines12030550","article-title":"Double trouble: how microbiome dysbiosis and mitochondrial dysfunction drive non-alcoholic fatty liver dis ease and non-alcoholic steatohepatitis","volume":"12","author":"Bahitham","year":"2024","journal-title":"biomedicines"},{"key":"B3","doi-asserted-by":"publisher","first-page":"17174","DOI":"10.3390\/ijms242417174","article-title":"Reduced lipopolysaccharide-bind ing protein (LBP) levels are associated with non-alcoholic fatty liver disea se (NAFLD) and adipose inflammation in human obesity","volume":"24","author":"Barchetta","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1002\/jcp.25435","article-title":"LPS induces hyper-permeabili ty of intestinal epithelial cells","volume":"232","author":"Bein","year":"","journal-title":"J. Cell Physiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1002\/jcp.25435","article-title":"LPS induces hyper-permeabili ty of intestinal epithelial cells","volume":"232","author":"Bein","year":"","journal-title":"J. Cell Physiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1016\/j.xphs.2015.11.018","article-title":"Reversible opening of intercell ular junctions of intestinal epithelial and brain endothelial cells with tight junction modulator peptides","volume":"105","author":"Bocsik","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of nonalcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1276790","DOI":"10.3389\/fmicb.2023.1276790","article-title":"Uncovering a causal connection between the Lachnoclostridium genus in fecal microbiota and non-alcoholic fatty liver diseas e: a two-sample Mendelian randomization analysis","volume":"14","author":"Dai","year":"","journal-title":"Front. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1276790","DOI":"10.3389\/fmicb.2023.1276790","article-title":"Uncovering a causal connection between the Lachnoclostridium genus in fecal microbiota and non-alcoholic fatty liver diseas e: a two-sample Mendelian randomization analysis","volume":"14","author":"Dai","year":"","journal-title":"Front. Microbiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/j.imbio.2017.01.003","article-title":"Hepatic interleukin-6 production is maintained during endotoxin tolerance and facilitates lipid accumulation","volume":"222","author":"Dembek","year":"2017","journal-title":"Immunobiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1039\/d2fo02463b","article-title":"Orally administered octacosanol improves liver insulin resistance in high-fat diet-fed mice through the reconstruction of the gut microbiota structure and inhibition of the TLR4\/NF-\u03baB inflammatory pathway way","volume":"14","author":"Ding","year":"2023","journal-title":"Food Funct."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e168","DOI":"10.1161\/ATV.0000000000000153","article-title":"Nonalcoholic fatty liver disease and cardiovascular risk: a scientific statement from the American heart associat ion","volume":"42","author":"Duell","year":"2022","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.3748\/wjg.v24.i27.2974","article-title":"Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: from \u201ctwo hit theory\u201d to \u201cmultiple hit model\u201d","volume":"24","author":"Fang","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"228","DOI":"10.3892\/mmr.2023.13115","article-title":"Dracocephalum moldavica L. extract alleviates experimental colitis in rats by modulating gut microbiome and inflammatory pathways athways","volume":"28","author":"Gang","year":"2023","journal-title":"Mol. Med. Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"3496","DOI":"10.3382\/ps\/pez153","article-title":"Protective effect of Salvia miltiorrhiza polys accharides on liver injury in chickens","volume":"98","author":"Han","year":"2019","journal-title":"Poult. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"106507","DOI":"10.1016\/j.phrs.2022.106507","article-title":"Toll-like receptors and metabolic (dysfuncti on)-associated fatty liver disease","volume":"185","author":"Khanmohammadi","year":"","journal-title":"Pharmacol. Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"106507","DOI":"10.1016\/j.phrs.2022.106507","article-title":"Toll-like receptors and metabolic (dysfuncti on)-associated fatty liver disease","volume":"185","author":"Khanmohammadi","year":"","journal-title":"Pharmacol. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3185","DOI":"10.3390\/molecules28073185","article-title":"Persistent lipid accumulation leads to persi stent exacerbation of endoplasmic reticulum stress and inflammation in progre ssive NASH via the IRE1\u03b1\/TRAF2 complex","volume":"28","author":"Lei","year":"2023","journal-title":"Molecules"},{"key":"B20","doi-asserted-by":"publisher","first-page":"6918","DOI":"10.3390\/molecules28196918","article-title":"Glucosamine improves non-alcoholic fatty Li ver disease induced by high-fat and high-sugar diet through regulating intes tinal barrier function, liver inflammation, and lipid metabolism","volume":"28","author":"Li","year":"2023","journal-title":"Molecules"},{"key":"B21","doi-asserted-by":"publisher","first-page":"105420","DOI":"10.1016\/j.phrs.2021.105420","article-title":"The role of short-chain fatty acids in intesti nal barrier function, inflammation, oxidative stress, and colonic carcinogenesis","volume":"165","author":"Liu","year":"","journal-title":"Pharmacol. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2 13","DOI":"10.1016\/j.freeradbiomed.2022.10.270","article-title":"The gut microbiota metabolite glycochenodeoxy cholate activates TFR-ACSL4-mediated ferroptosis to promote the development of environmental toxin-linked MAFLD","volume":"193","author":"Liu","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"109019","DOI":"10.1016\/j.abb.2021.109019","article-title":"Luteolin alleviates non-alcoholic fatty liver disea se in rats via restoration of intestinal mucosal barrier damage and microbiota i mbalance involving in gut-liver axis","volume":"711","author":"Liu","year":"","journal-title":"Arch. Biochem. Biophys."},{"key":"B24","doi-asserted-by":"publisher","first-page":"121614","DOI":"10.1016\/j.lfs.2023.121614","article-title":"Gut-liver axis in the progression of nonalcoholic fatty liver disease: from the microbial derivatives-centered perspective","volume":"321","author":"Luo","year":"2023","journal-title":"Life Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"6911","DOI":"10.3748\/wjg.v19.i40.6911","article-title":"Effects of probiotics on nonalcoholic fatty live r disease: a meta-analysis","volume":"19","author":"Ma","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1002\/hep.22399","article-title":"Beyond insulin resistance: innate immunity in nonalcoholic steatohepatitis","volume":"48","author":"Maher","year":"2008","journal-title":"Hepatology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3278","DOI":"10.3390\/ijms25063278","article-title":"Inflammatory bowel diseases and No n-alcoholic fatty liver disease: piecing a complex puzzle together","volume":"25","author":"Maresca","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"112680","DOI":"10.1016\/j.phytochem.2021.112680","article-title":"Abietane diterpenoids from Dracocephalum mo ldavica L. and their anti-inflammatory activities in vitro","volume":"1","author":"Nie","year":"2021","journal-title":"Phytochemistry"},{"key":"B29","doi-asserted-by":"publisher","first-page":"426","DOI":"10.3390\/ijms23010426","article-title":"Role of microbiota-derived metabolites i n alcoholic and non-alcoholic fatty liver diseases","volume":"23","author":"Park","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"116848","DOI":"10.1016\/j.jep.2023.116848","article-title":"Zanthoxylum bungeanum amides ameliorates nonalcoholic fatty liver via regulating gut microbiota and activating AMPK\/Nrf 2 signaling","volume":"318","author":"Peng","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1159\/000535524","article-title":"Mechanisms and therapeutic strategies for MA FLD targeting TLR4 signaling pathways","volume":"16","author":"Ren","year":"","journal-title":"J. Innate Immun."},{"key":"B32","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1159\/000535524","article-title":"Mechanisms and therapeutic strategies for MA FLD targeting TLR4 signaling pathways","volume":"16","author":"Ren","year":"","journal-title":"J. Innate Immun."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1007\/s00018-019-03011-w","article-title":"The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD)","volume":"76","author":"Safari","year":"2019","journal-title":"Cell Mol. Life Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.3390\/ijms23052764","article-title":"Natural compounds for counteracting nonalcoholic fatty liver disease (NAFLD): advantages and limitations of the suggested candidates","volume":"23","author":"Salvoza","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"G270","DOI":"10.1152\/ajpgi.00304.2014","article-title":"Hepatic TLR4 signaling in obese NAFLD","volume":"309","author":"Sharifnia","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1080\/13880209.2022.2126503","article-title":"Gypenosides counteract hepatic steatosis and intestinal barrier injury in rats with metabolic associated fatty liver disease by modulating the adenosine monophosphate activated protein kinase and Toll-like receptor 4\/nuclear factor kappa B pathways","volume":"60","author":"Shen","year":"2022","journal-title":"Pharm. Biol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"3042","DOI":"10.1080\/15384101.2020.1829800","article-title":"Gypenosides improves nonalcoholic fatty liver disease induced by high-fat diet induced through regulating LPS\/TLR4 signaling pathway ng pathway","volume":"19","author":"Shen","year":"2020","journal-title":"Cell Cycle"},{"key":"B38","doi-asserted-by":"publisher","first-page":"524","DOI":"10.3390\/biomedicines10030524","article-title":"The role of gut-liver Axis in gut microbiome dysbios is associated NAFLD and NAFLD-HCC","volume":"10","author":"Song","year":"2022","journal-title":"Biomedicines"},{"key":"B39","doi-asserted-by":"publisher","first-page":"3460","DOI":"10.3390\/nu12113460","article-title":"The relationship between prebiotic supplementation and anthropometric and biochemical parameters in patients with NAFLD-A systematic review and meta-analysis of randomized controlled trials","volume":"12","author":"Stachowska","year":"2020","journal-title":"Nutrients"},{"key":"B40","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1080\/17474124.2019.1569513","article-title":"Gut microbiota: novel therapeutic target for nonalcoholic fatty liver disease","volume":"13","author":"Suk","year":"2019","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1136\/gutjnl-2023-330595","article-title":"MASLD: a systemic metabolic disorder with cardiovascular and malignant complications","volume":"73","author":"Targher","year":"2024","journal-title":"Gut"},{"key":"B42","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/s41575-018-0011-z","article-title":"The gut-liver axis and the inters ection with the microbiome","volume":"15","author":"Tripathi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1136\/gutjnl-2021-324915","article-title":"Epidemiological trends and t rajectories of MAFLD-associated hepatocellular carcinoma 2002-2033. The ITA. LI.CA database","volume":"72","author":"Vitale","year":"2023","journal-title":"Gut"},{"key":"B44","doi-asserted-by":"publisher","first-page":"902","DOI":"10.5152\/tjg.2020.19568","article-title":"Berberine inhibits liver damage in rats with non-alcoholic fatty liver disease by regulating TLR4\/MyD88\/NF-\u03baB pathway","volume":"31","author":"Wang","year":"2020","journal-title":"Turk J. Gastroenterol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41423-020-00592-6","article-title":"Gut microbiome, liver immunology, and liver diseases","volume":"18","author":"Wang","year":"2021","journal-title":"Cell Mol. Immunol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/978-981-10-8684-7_12","article-title":"Current prevention and treatment options for NAFLD","volume":"1061","author":"Wong","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1998","DOI":"10.1111\/jgh.15025","article-title":"Regulation of lipid-induced macrophage pol arization through modulating peroxisome proliferator-activated receptor-gamma a ctivity affects hepatic lipid metabolism via a Toll-like receptor 4\/NF-\u03baB signal ing pathway","volume":"35","author":"Wu","year":"2020","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2221450","DOI":"10.1080\/19490976.2023.2221450","article-title":"Resynchronized rhythmic oscillations of gut mi crobiota drive time-restricted feeding induced nonalcoholic steatohepatitis allevia tion","volume":"15","author":"Xia","year":"2023","journal-title":"Gut Microbes"},{"key":"B49","doi-asserted-by":"publisher","first-page":"3592","DOI":"10.3748\/wjg.v13.i26.3592","article-title":"Dynamic changes and mechanism of intestinal endotoxemia in partially hepatectomized rats","volume":"13","author":"Xu","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"166480","DOI":"10.1016\/j.bbadis.2022.166480","article-title":"Macrophage-specific MyD88 deletion and pharmacological inhibition prevents liver damage in non-alcoholic fatty liver dis ease via reducing inflammatory response","volume":"1868","author":"Yang","year":"2022","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"112309","DOI":"10.1016\/j.foodres.2022.112309","article-title":"Inulin intervention attenuates hepatic steatosis i n rats via modulating gut microbiota and maintaining intestinal barrier function","volume":"163","author":"Yang","year":"2023","journal-title":"Food Res. Int."},{"key":"B52","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1159148","DOI":"10.3389\/fendo.2023.1159148","article-title":"Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study","volume":"14","author":"Zhang","year":"","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1117644","DOI":"10.3389\/fmicb.2023.1117644","article-title":"Vitamin D alleviates non-alcoholic fatty l iver disease via restoring gut microbiota and metabolism","volume":"14","author":"Zhang","year":"","journal-title":"Front. Microbiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"e0004722","DOI":"10.1128\/spectrum.00047-22","article-title":"Longitudinal 16S rRNA sequencing reveals R elationships among alterations of gut microbiota and nonalcoholic fatty liver disease progression in mice","volume":"10","author":"Zhuge","year":"2022","journal-title":"Microbiol. Spectr."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1549515\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T05:31:12Z","timestamp":1747287072000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1549515\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":55,"alternative-id":["10.3389\/fphar.2025.1549515"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1549515","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,15]]},"article-number":"1549515"}}