{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:32:13Z","timestamp":1791495133152,"version":"4.3.4"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"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>Background and purpose<\/jats:title><jats:p>As a traditional Chinese medicine formula, Yangyinghuoxue Decoction (YYHXD) is used clinically for therapy of hepatic fibrosis. The pharmacological profile of YYHXD comprises multiple components acting on many targets and pathways, but the pharmacological mechanisms underlying its efficacy have not been thoroughly elucidated. This study aimed at probing the pharmacological mechanisms of YYHXD in the treatment of hepatic fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>YYHXD aqueous extract was prepared and quality control using HPLC-MS fingerprint analysis was performed. A CCl<jats:sub>4<\/jats:sub>-induced rat model of hepatic fibrosis was established, and animals were randomly assigned to six groups: control, low-dose YYHXD (L-YYHXD), medium-dose YYHXD (M-YYHXD), high-dose YYHXD (H-YYHXD), CCl4 model, and colchicine group. Rats in the treatment groups received daily oral administration of YYHXD (5, 10, or 20\u00a0g\/kg) or colchicine (0.2\u00a0mg\/kg) for 6\u00a0weeks, while the control and model groups received distilled water. Histological analysis, including hematoxylin and eosin (HE) and Masson\u2019s trichrome staining, was performed to evaluate hepatic fibrosis. Serum biochemical markers, such as AST, ALT, HA, and LN, were measured. Inflammatory cytokines (IL-6 and TNF-\u03b1) and oxidative stress indicators (SOD, GSH-Px, and MDA) in hepatic tissue were also assessed. Additionally, transcriptomic analysis using RNA-sequencing was conducted to identify differentially expressed genes (DEGs) between the control, CCl4 model, and H-YYHXD groups. Bioinformatics analysis, including differential expression analysis, protein-protein interaction analysis, and functional enrichment analysis, were performed to probe the pharmacological mechanisms of YYHXD. The regulatory effects of YYHXD on fatty acid metabolism and biosynthesis were further confirmed by Oil Red O staining, enzyme activity assays, qPCR, and Western blotting. Western blotting and immunofluorescence staining also validated the involvement of the AMPK signaling pathway in the occurrence and progression of hepatic fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HE and Masson\u2019s trichrome staining revealed reduced collagen deposition and improved liver architecture in YYHXD groups compared to the CCl<jats:sub>4<\/jats:sub> model group. Serum biochemical markers, including AST, ALT, HA, and LN, were significantly improved in the YYHXD-treated groups compared to the CCl<jats:sub>4<\/jats:sub> model group. The levels of inflammatory cytokines (IL-6 and TNF-\u03b1) and oxidative stress indicators (decreased SOD and GSH-Px, increased MDA) in hepatic tissue were significantly ameliorated by YYHXD treatment compared to the CCl<jats:sub>4<\/jats:sub> model group. Moreover, 96 genes implicated in YYHXD therapy of hepatic fibrosis were screened from the transcriptomic data, which were principally enriched in biological pathways such as fatty acid metabolism and biosynthesis, and the AMPK signaling pathway. Oil Red O staining showed reduced hepatic lipid accumulation by YYHXD in a dose-dependent manner, along with decreased serum TG, TC, and LDL-C levels. Additionally, qPCR and Western blot analyses demonstrated upregulated mRNA and protein expression of key enzymes involved in fatty acid metabolism and biosynthesis, Fasn and Fads2, modulated by YYHXD. YYHXD also dose-dependently enhanced phosphorylation of AMPK as evidenced by Western blotting and immunofluorescence assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>YYHXD ameliorated CCl<jats:sub>4<\/jats:sub>-induced hepatic fibrosis in rats through pharmacological mechanisms that involved manifold targets and pathways, including aliphatic acid synthesis and metabolism pathways and the AMPK signaling pathway. This study provided a reference and basis for further research and clinical utilization of YYHXD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1364023","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T05:01:06Z","timestamp":1715749266000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptomic analysis reveals pharmacological mechanisms mediating efficacy of Yangyinghuoxue Decoction in CCl4-induced hepatic fibrosis in rats"],"prefix":"10.3389","volume":"15","author":[{"given":"Yanming","family":"Bai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"B1","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":"B2","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13020-016-0102-0","article-title":"Antioxidant and physiological effects of Si-Wu-Tang on skin and liver: a randomized, double-blind, placebo-controlled clinical trial","volume":"11","author":"Chiu","year":"2016","journal-title":"Chin. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3595","DOI":"10.2147\/DDDT.S179876","article-title":"Asiatic acid ameliorates CCl4-induced liver fibrosis in rats: involvement of Nrf2\/ARE, NF-\u03baB\/I\u03baB\u03b1, and JAK1\/STAT3 signaling pathways","volume":"12","author":"Fan","year":"2018","journal-title":"Drug Des. Devel Ther."},{"key":"B4","doi-asserted-by":"publisher","first-page":"154587","DOI":"10.1016\/j.phymed.2022.154587","article-title":"Glycyrrhizic acid alleviates liver fibrosis in vitro and in vivo via activating CUGBP1-mediated IFN-\u03b3\/STAT1\/Smad7 pathway","volume":"112","author":"Guo","year":"2023","journal-title":"Phytomedicine"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1002\/1873-3468.14134","article-title":"Ablation of fatty acid desaturase 2 (FADS2) exacerbates hepatic triacylglycerol and cholesterol accumulation in polyunsaturated fatty acid-depleted mice","volume":"595","author":"Hayashi","year":"2021","journal-title":"Febs. Lett."},{"key":"B6","doi-asserted-by":"publisher","first-page":"101238","DOI":"10.1016\/j.molmet.2021.101238","article-title":"Metabolic-associated fatty liver disease and lipoprotein metabolism","volume":"50","author":"Heeren","year":"2021","journal-title":"Mol. Metab."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3056","DOI":"10.1002\/hep.32066","article-title":"Salidroside activates the AMP-activated protein kinase pathway to suppress nonalcoholic steatohepatitis in mice","volume":"74","author":"Hu","year":"2021","journal-title":"Hepatology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"153739","DOI":"10.1016\/j.phymed.2021.153739","article-title":"Activation of AMPK by triptolide alleviates nonalcoholic fatty liver disease by improving hepatic lipid metabolism, inflammation and fibrosis","volume":"92","author":"Huang","year":"2021","journal-title":"Phytomedicine"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1038\/s41374-020-0457-9","article-title":"Cholestasis impairs hepatic lipid storage via AMPK and CREB signaling in hepatitis B virus surface protein transgenic mice","volume":"100","author":"Irungbam","year":"2020","journal-title":"Lab. Invest."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.3390\/cells11091500","article-title":"Recent advancements in antifibrotic therapies for regression of liver fibrosis","volume":"11","author":"Jangra","year":"2022","journal-title":"Cells"},{"key":"B11","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.cbi.2007.05.008","article-title":"Combined metadoxine and garlic oil treatment efficaciously abrogates alcoholic steatosis and CYP2E1 induction in rat liver with restoration of AMPK activity","volume":"169","author":"Ki","year":"2007","journal-title":"Chem. Biol. Interact."},{"key":"B12","doi-asserted-by":"publisher","first-page":"29423","DOI":"10.1038\/srep29423","article-title":"CHIP(-\/-)-mouse liver: adiponectin-AMPK-FOXO activation overrides CYP2E1-elicited JNK1 activation, delaying onset of NASH: therapeutic implications","volume":"6","author":"Kim","year":"2016","journal-title":"Sci. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1111\/jgh.12147","article-title":"Paeonol inhibits hepatic fibrogenesis via disrupting nuclear factor-\u03baB pathway in activated stellate cells: in vivo and in vitro studies","volume":"28","author":"Kong","year":"2013","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.16781\/j.CN31-2187\/R.20230107","article-title":"Protective effect of Jinyin Lidan capsule on carbon tetrachloride-induced hepatic fibrosis in rats","volume":"44","author":"Kong","year":"2023","journal-title":"Acad. J. Nav. Med. Univ."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.3390\/ijms22031272","article-title":"Fatty acids and a high-fat diet induce epithelial-mesenchymal transition by activating TGF\u03b2 and \u03b2-catenin in liver cells","volume":"22","author":"Kwapisz","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1080\/15548627.2020.1712108","article-title":"SQSTM1\/p62 activates NFE2L2\/NRF2 via ULK1-mediated autophagic KEAP1 degradation and protects mouse liver from lipotoxicity","volume":"16","author":"Lee","year":"","journal-title":"Autophagy"},{"key":"B17","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1080\/13880209.2020.1750658","article-title":"Emodin in Rheum undulatum inhibits oxidative stress in the liver via AMPK with Hippo\/Yap signalling pathway","volume":"58","author":"Lee","year":"","journal-title":"Pharm. Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"967623","DOI":"10.3389\/fphar.2022.967623","article-title":"Chaihu Shugan powder alleviates liver inflammation and hepatic steatosis in NAFLD mice: a network pharmacology study and in vivo experimental validation","volume":"13","author":"Lei","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"109734","DOI":"10.1016\/j.biopha.2019.109734","article-title":"Huang-Qi San improves glucose and lipid metabolism and exerts protective effects against hepatic steatosis in high fat diet-fed rats","volume":"126","author":"Li","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"B20","doi-asserted-by":"publisher","first-page":"493","DOI":"10.13621\/j.1001-5949.2022.06.0493","article-title":"Effect of Yangying huoxue decoction on TGF-\u03b21 and EMT in rats with hepatic fibrosis","volume":"44","author":"Liang","year":"2022","journal-title":"Ningxia. Med. J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"86","DOI":"10.20065\/j.cnki.btcm.20230110","article-title":"Treatment of primary liver cancer from nutreint deficiency and blood Stasis","volume":"2","author":"Liang","year":"2023","journal-title":"Basic. Tradit. Chin. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"113364","DOI":"10.1016\/j.jep.2020.113364","article-title":"An integrated network pharmacology and RNA-Seq approach for exploring the preventive effect of Lonicerae japonicae flos on LPS-induced acute lung injury","volume":"264","author":"Liu","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1021\/np300509z","article-title":"Hepatoprotective iridoid glycosides from the roots of Rehmannia glutinosa","volume":"75","author":"Liu","year":"2012","journal-title":"J. Nat. Prod."},{"key":"B24","doi-asserted-by":"publisher","first-page":"254","DOI":"10.16050\/j.cnki.issn1674-6309.2018.03.002","article-title":"Effects of Yangyinghuoxue Decoction based on Wnt\/\u03b2-catenin signaling pathway on Wnt1, \u03b2-catenin and TGF-\u03b21 in rats with liver fibrosis","volume":"40","author":"Ma","year":"2018","journal-title":"Ningxia. Med. Univ. J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"113834","DOI":"10.1016\/j.biopha.2022.113834","article-title":"Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment","volume":"155","author":"Ma","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"B26","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s12192-022-01286-w","article-title":"Modulation of endoplasmic reticulum stress via sulforaphane-mediated AMPK upregulation against nonalcoholic fatty liver disease in rats","volume":"27","author":"Mansour","year":"2022","journal-title":"Cell. Stress. Chaperones."},{"key":"B27","doi-asserted-by":"publisher","first-page":"265","DOI":"10.3390\/ijms21010265","article-title":"Cryptotanshinone from the Salvia miltiorrhiza bunge attenuates ethanol-induced liver injury by activation of AMPK\/SIRT1 and Nrf2 signaling pathways","volume":"21","author":"Nagappan","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"15661","DOI":"10.1038\/s41598-022-19459-z","article-title":"FASN inhibition targets multiple drivers of NASH by reducing steatosis, inflammation and fibrosis in preclinical models","volume":"12","author":"O'Farrell","year":"2022","journal-title":"Sci. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.jhep.2014.10.039","article-title":"Molecular mechanism of PPAR\u03b1 action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease","volume":"62","author":"Pawlak","year":"2015","journal-title":"J. Hepatol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"762","DOI":"10.3389\/fphar.2018.00762","article-title":"Salvia miltiorrhiza ameliorates liver fibrosis by activating hepatic natural killer cells in vivo and in vitro","volume":"9","author":"Peng","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s11418-022-01647-w","article-title":"Andrographolide ameliorates hepatic steatosis by suppressing FATP2-mediated fatty acid uptake in mice with nonalcoholic fatty liver disease","volume":"77","author":"Ran","year":"2023","journal-title":"J. Nat. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3406","DOI":"10.3390\/cells10123406","article-title":"Maresin-1 prevents liver fibrosis by targeting Nrf2 and NF-\u03baB, reducing oxidative stress and inflammation","volume":"10","author":"Rodr\u00edguez","year":"2021","journal-title":"Cells"},{"key":"B33","doi-asserted-by":"publisher","first-page":"5166","DOI":"10.1210\/en.2003-0849","article-title":"Minireview: malonyl CoA, AMP-activated protein kinase, and adiposity","volume":"144","author":"Ruderman","year":"2003","journal-title":"Endocrinology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2767","DOI":"10.3892\/mmr.2017.6895","article-title":"Inhibition of aldose reductase ameliorates alcoholic liver disease by activating AMPK and modulating oxidative stress and inflammatory cytokines","volume":"16","author":"Shi","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"G739","DOI":"10.1152\/ajpgi.00432.2010","article-title":"Activated AMPK inhibits PPAR-{alpha} and PPAR-{gamma} transcriptional activity in hepatoma cells","volume":"301","author":"Sozio","year":"2011","journal-title":"Am. J. physiology. Am. J. Physiol. Gastrointest. Liver. Physiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1507\/endocrj.ej12-0271","article-title":"Adipose tissue inflammation and ectopic lipid accumulation","volume":"59","author":"Suganami","year":"2012","journal-title":"Endocr. J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"4087","DOI":"10.3390\/foods11244087","article-title":"A homogalacturonan from peel of Winter Jujube (Zizyphus jujuba Mill. cv. Dongzao): characterization and protective effects against CCl4-induced liver injury","volume":"11","author":"Sun","year":"2022","journal-title":"Foods"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1002\/hep.29914","article-title":"Neutrophil extracellular traps promote inflammation and development of hepatocellular carcinoma in nonalcoholic steatohepatitis","volume":"68","author":"van der Windt","year":"2018","journal-title":"Hepatology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/j.1748-1716.2009.01970.x","article-title":"AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives","volume":"196","author":"Viollet","year":"2009","journal-title":"Acta. Physiol. (Oxf)."},{"key":"B40","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.fitote.2010.04.007","article-title":"Chemical composition and inhibitory effect on hepatic fibrosis of Danggui Buxue Decoction","volume":"81","author":"Wang","year":"2010","journal-title":"Fitoterapia"},{"key":"B41","doi-asserted-by":"publisher","first-page":"985935","DOI":"10.3389\/fphar.2022.985935","article-title":"Efficacy, chemical composition, and pharmacological effects of herbal drugs derived from Fritillaria cirrhosa D. Don and Fritillaria thunbergii Miq","volume":"13","author":"Wu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"618846","DOI":"10.3389\/fphar.2021.618846","article-title":"Systems pharmacology study of the anti-liver injury mechanism of Citri reticulatae Pericarpium","volume":"12","author":"Wu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1142\/S0192415X11009482","article-title":"Hot water extracted Lycium barbarum and Rehmannia glutinosa inhibit liver inflammation and fibrosis in rats","volume":"39","author":"Wu","year":"2011","journal-title":"Am. J. Chin. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1002\/iub.1348","article-title":"Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3 inflammasome pathway","volume":"67","author":"Wu","year":"2015","journal-title":"IUBMB. Life."},{"key":"B45","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s13020-021-00524-0","article-title":"Si-Wu-Tang ameliorates fibrotic liver injury via modulating intestinal microbiota and bile acid homeostasis","volume":"16","author":"Xue","year":"2021","journal-title":"Chin. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.chembiol.2021.07.022","article-title":"FADS2-dependent fatty acid desaturation dictates cellular sensitivity to ferroptosis and permissiveness for hepatitis C virus replication","volume":"29","author":"Yamane","year":"2022","journal-title":"Cell. Chem. Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.1111\/jcmm.17277","article-title":"Multi-faceted role of pyroptosis mediated by inflammasome in liver fibrosis","volume":"26","author":"Yang","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"645","DOI":"10.7150\/ijbs.7.645","article-title":"Mechanism of AMPK suppression of LXR-dependent Srebp-1c transcription","volume":"7","author":"Yap","year":"2011","journal-title":"Int. J. Biol. Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2700","DOI":"10.3168\/jds.2022-22021","article-title":"Liver fibrosis is a common pathological change in the liver of dairy cows with fatty liver","volume":"106","author":"Zhang","year":"2023","journal-title":"J. Dairy. Sci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"111833","DOI":"10.1016\/j.biopha.2021.111833","article-title":"Application of omics- and multi-omics-based techniques for natural product target discovery","volume":"141","author":"Zhang","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1638740","DOI":"10.1155\/2022\/1638740","article-title":"A network pharmacology study on the active components and targets of the Radix ginseng and Radix Bupleuri herb pair for treating nonalcoholic fatty liver disease","volume":"2022","author":"Zhang","year":"","journal-title":"Evid. Based. Complement. Altern. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.rvsc.2013.01.028","article-title":"Up-regulation of components of the renin-angiotensin system in liver fibrosis in the rat induced by CCL4","volume":"95","author":"Zhang","year":"2013","journal-title":"Res. Vet. Sci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3892\/ijo.2022.5421","article-title":"Eupalinolide A induces autophagy via the ROS\/ERK signaling pathway in hepatocellular carcinoma cells in vitro and in vivo","volume":"61","author":"Zhang","year":"","journal-title":"Int. J. Oncol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"12279","DOI":"10.1074\/jbc.REV120.011356","article-title":"From overnutrition to liver injury: AMP-activated protein kinase in nonalcoholic fatty liver diseases","volume":"295","author":"Zhao","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B55","article-title":"Clinical observation on 80 cases of liver fibrosis treated with Yangyinghuoxue Decoction. Clin. Psychosom","author":"Zhou","year":"2015","journal-title":"Dis. P61."},{"key":"B56","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.fsi.2018.08.047","article-title":"The hepatoprotective effects of Radix Bupleuri extracts against D-galactosamine\/lipopolysaccharide induced liver injury in hybrid grouper (Epinephelus lanceolatus\u2642 \u00d7 Epinephelus fuscoguttatus\u2640)","volume":"83","author":"Zou","year":"2018","journal-title":"Fish. Shellfish. Immunol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1364023\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T05:01:14Z","timestamp":1715749274000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1364023\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":56,"alternative-id":["10.3389\/fphar.2024.1364023"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1364023","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,15]]},"article-number":"1364023"}}