{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:45:30Z","timestamp":1790390730903,"version":"4.1.0"},"reference-count":55,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"name":"National High Technology Research and Development Program of China","award":["2014AA020705"],"award-info":[{"award-number":["2014AA020705"]}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2019,6]]},"DOI":"10.1016\/j.ejphar.2019.02.039","type":"journal-article","created":{"date-parts":[[2019,2,25]],"date-time":"2019-02-25T02:45:19Z","timestamp":1551062719000},"page":"58-67","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"special_numbering":"C","title":["Dihydromyricetin attenuates hypertrophic scar formation by targeting activin receptor-like kinase 5"],"prefix":"10.1016","volume":"852","author":[{"given":"Xiaolu","family":"Ye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiying","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningwen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2019.02.039_bib1","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.1096\/fj.07-8218com","article-title":"Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis","volume":"21","author":"Aarabi","year":"2007","journal-title":"FASEB J."},{"key":"10.1016\/j.ejphar.2019.02.039_bib2","doi-asserted-by":"crossref","first-page":"e234","DOI":"10.1371\/journal.pmed.0040234","article-title":"Hypertrophic scar formation following burns and trauma: new approaches to treatment","volume":"4","author":"Aarabi","year":"2007","journal-title":"PLoS Med."},{"key":"10.1016\/j.ejphar.2019.02.039_bib3","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.burns.2014.02.011","article-title":"Up-to-date approach to manage keloids and hypertrophic scars: a useful guide","volume":"40","author":"Arno","year":"2014","journal-title":"Burns"},{"key":"10.1016\/j.ejphar.2019.02.039_bib4","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1021\/cb5008376","article-title":"Small molecule substrate phosphorylation site inhibitors of protein kinases: approaches and challenges","volume":"10","author":"Breen","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.ejphar.2019.02.039_bib5","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1097\/PRS.0b013e3181e3b804","article-title":"The most current algorithms for the treatment and prevention of hypertrophic scars and keloids","volume":"126","author":"Caviggioli","year":"2010","journal-title":"Plast. Reconstr. Surg."},{"key":"10.1016\/j.ejphar.2019.02.039_bib6","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/j.1742-481X.2011.00771.x","article-title":"The evidence for the role of transforming growth factor-beta in the formation of abnormal scarring","volume":"8","author":"Chalmers","year":"2011","journal-title":"Int. Wound J."},{"key":"10.1016\/j.ejphar.2019.02.039_bib7","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.phrs.2015.05.009","article-title":"Dihydromyricetin improves glucose and lipid metabolism and exerts anti-inflammatory effects in nonalcoholic fatty liver disease: a randomized controlled trial","volume":"99","author":"Chen","year":"2015","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.ejphar.2019.02.039_bib8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1358\/dnp.2006.19.2.977444","article-title":"Inhibition of ALK5 as a new approach to treat liver fibrotic diseases","volume":"19","author":"de Gouville","year":"2006","journal-title":"Drug News Perspect."},{"key":"10.1016\/j.ejphar.2019.02.039_bib9","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3009337","article-title":"Wound repair and regeneration: mechanisms, signaling, and translation","volume":"6","author":"Eming","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ejphar.2019.02.039_bib10","doi-asserted-by":"crossref","first-page":"9758","DOI":"10.3892\/mmr.2017.7802","article-title":"Inhibition of human lung cancer proliferation through targeting stromal fibroblasts by dihydromyricetin","volume":"16","author":"Fan","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.ejphar.2019.02.039_bib11","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1242\/jcs.024521","article-title":"Myofibroblast communication is controlled by intercellular mechanical coupling","volume":"121","author":"Follonier","year":"2008","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.ejphar.2019.02.039_bib12","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2119\/molmed.2009.00153","article-title":"Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies","volume":"17","author":"Gauglitz","year":"2011","journal-title":"Mol. Med."},{"key":"10.1016\/j.ejphar.2019.02.039_bib13","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1038\/sj.jid.5700890","article-title":"TNF-alpha suppresses alpha-smooth muscle actin expression in human dermal fibroblasts: an implication for abnormal wound healing","volume":"127","author":"Goldberg","year":"2007","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.ejphar.2019.02.039_bib14","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/nature07039","article-title":"Wound repair and regeneration","volume":"453","author":"Gurtner","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2019.02.039_bib15","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jphotobiol.2016.05.002","article-title":"Apoptosis inhibition effect of Dihydromyricetin against UVA-exposed human keratinocyte cell line","volume":"161","author":"He","year":"2016","journal-title":"J. Photochem. Photobiol. B"},{"key":"10.1016\/j.ejphar.2019.02.039_bib16","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/37284","article-title":"TGF-beta signalling from cell membrane to nucleus through SMAD proteins","volume":"390","author":"Heldin","year":"1997","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2019.02.039_bib17","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1091\/mbc.12.9.2730","article-title":"Alpha-smooth muscle actin expression upregulates fibroblast contractile activity","volume":"12","author":"Hinz","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.ejphar.2019.02.039_bib18","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/978-1-62703-505-7_11","article-title":"Novel methods for the investigation of human hypertrophic scarring and other dermal fibrosis","volume":"1037","author":"Honardoust","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.ejphar.2019.02.039_bib19","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.lfs.2015.03.007","article-title":"Dihydromyricetin protects endothelial cells from hydrogen peroxide-induced oxidative stress damage by regulating mitochondrial pathways","volume":"130","author":"Hou","year":"2015","journal-title":"Life Sci."},{"key":"10.1016\/j.ejphar.2019.02.039_bib20","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1021\/acs.jnatprod.5b00275","article-title":"Suppression of inflammatory responses by dihydromyricetin, a flavonoid from ampelopsis grossedentata, via inhibiting the activation of NF-kappaB and MAPK signaling pathways","volume":"78","author":"Hou","year":"2015","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.ejphar.2019.02.039_bib21","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1177\/1087057111405846","article-title":"Screening and identification of a novel class of TGF-beta type 1 receptor kinase inhibitor","volume":"16","author":"Huynh","year":"2011","journal-title":"J. Biomol. Screen"},{"issue":"Suppl. 1","key":"10.1016\/j.ejphar.2019.02.039_bib22","first-page":"S40","article-title":"Hypertrophic scar model in the rabbit ear: a reproducible model for studying scar tissue behavior with new observations on silicone gel sheeting for scar reduction","volume":"15","author":"Kloeters","year":"2007","journal-title":"Wound Repair Regen."},{"key":"10.1016\/j.ejphar.2019.02.039_bib23","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00018-013-1349-6","article-title":"The pathogenesis of cardiac fibrosis","volume":"71","author":"Kong","year":"2014","journal-title":"Cell Mol. Life Sci."},{"key":"10.1016\/j.ejphar.2019.02.039_bib24","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S1471-4892(03)00002-X","article-title":"ALK5 inhibition in renal disease","volume":"3","author":"Laping","year":"2003","journal-title":"Curr. Opin. Pharmacol."},{"key":"10.1016\/j.ejphar.2019.02.039_bib25","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1111\/dsu.12346","article-title":"Intralesional treatment for keloids and hypertrophic scars: a review","volume":"39","author":"Ledon","year":"2013","journal-title":"Dermatol. Surg."},{"key":"10.1016\/j.ejphar.2019.02.039_bib26","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3109\/10799893.2015.1024852","article-title":"Identification of ALK5 inhibitor via structure-based virtual screening and ADMET prediction","volume":"35","author":"Lin","year":"2015","journal-title":"J. Recept. Signal Transduct. Res"},{"key":"10.1016\/j.ejphar.2019.02.039_bib27","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.3892\/mmr.2014.2891","article-title":"Dihydromyricetin induces mouse hepatoma Hepal-6 cell apoptosis via the transforming growth factor-beta pathway","volume":"11","author":"Liu","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.ejphar.2019.02.039_bib28","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1038\/jid.2014.169","article-title":"Mesenchymal stem cells prevent hypertrophic scar formation via inflammatory regulation when undergoing apoptosis","volume":"134","author":"Liu","year":"2014","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.ejphar.2019.02.039_bib29","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1038\/jid.2012.486","article-title":"Xiamenmycin attenuates hypertrophic scars by suppressing local inflammation and the effects of mechanical stress","volume":"133","author":"Liu","year":"2013","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.ejphar.2019.02.039_bib30","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0092-8674(00)00121-5","article-title":"TGFbeta signaling in growth control, cancer, and heritable disorders","volume":"103","author":"Massague","year":"2000","journal-title":"Cell"},{"key":"10.1016\/j.ejphar.2019.02.039_bib31","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1093\/emboj\/19.8.1745","article-title":"Transcriptional control by the TGF-beta\/Smad signaling system","volume":"19","author":"Massague","year":"2000","journal-title":"EMBO J."},{"key":"10.1016\/j.ejphar.2019.02.039_bib32","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrneph.2016.48","article-title":"TGF-beta: the master regulator of fibrosis","volume":"12","author":"Meng","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"10.1016\/j.ejphar.2019.02.039_bib33","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1146\/annurev-physiol-022516-034339","article-title":"Macrophage polarization","volume":"79","author":"Murray","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"10.1016\/j.ejphar.2019.02.039_bib34","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1097\/00006534-199910000-00031","article-title":"On the nature of hypertrophic scars and keloids: a review","volume":"104","author":"Niessen","year":"1999","journal-title":"Plast. Reconstr. Surg."},{"key":"10.1016\/j.ejphar.2019.02.039_bib35","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1007\/s00018-014-1798-6","article-title":"EW-7197 inhibits hepatic, renal, and pulmonary fibrosis by blocking TGF-beta\/Smad and ROS signaling","volume":"72","author":"Park","year":"2015","journal-title":"Cell Mol. Life Sci."},{"key":"10.1016\/j.ejphar.2019.02.039_bib36","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.ejmech.2014.09.002","article-title":"Design, synthesis and evaluation of small molecule imidazo[2,1-b][1,3,4]thiadiazoles as inhibitors of transforming growth factor-beta type-I receptor kinase (ALK5)","volume":"93","author":"Patel","year":"2015","journal-title":"Eur. J. Med. Chem."},{"issue":"1\u201310","key":"10.1016\/j.ejphar.2019.02.039_bib37","first-page":"11","article-title":"Cutaneous scarring: Pathophysiology, molecular mechanisms, and scar reduction therapeutics Part I. The molecular basis of scar formation","volume":"66","author":"Profyris","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"10.1016\/j.ejphar.2019.02.039_bib38","first-page":"1880","article-title":"Suppression of transforming growth factor-beta effects in rabbit subconjunctival fibroblasts by activin receptor-like kinase 5 inhibitor","volume":"16","author":"Sapitro","year":"2010","journal-title":"Mol. Vis."},{"issue":"Suppl 1","key":"10.1016\/j.ejphar.2019.02.039_bib39","first-page":"10","article-title":"Mechanisms of pathological scarring: role of myofibroblasts and current developments","volume":"19","author":"Sarrazy","year":"2011","journal-title":"Wound Repair Regen."},{"key":"10.1016\/j.ejphar.2019.02.039_bib40","first-page":"362","article-title":"Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair","author":"Shook","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.ejphar.2019.02.039_bib41","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ejphar.2017.04.014","article-title":"Dihydromyricetin attenuated Ang II induced cardiac fibroblasts proliferation related to inhibitory of oxidative stress","volume":"807","author":"Song","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2019.02.039_bib42","first-page":"959","article-title":"Comparison of transforming growth factor-beta\/Smad signaling between normal dermal fibroblasts and fibroblasts derived from central and peripheral areas of keloid lesions","volume":"19","author":"Tsujita-Kyutoku","year":"2005","journal-title":"In Vivo"},{"key":"10.1016\/j.ejphar.2019.02.039_bib43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.burns.2008.06.020","article-title":"Potential cellular and molecular causes of hypertrophic scar formation","volume":"35","author":"van der Veer","year":"2009","journal-title":"Burns"},{"key":"10.1016\/j.ejphar.2019.02.039_bib44","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1038\/labinvest.2008.101","article-title":"Deep dermal fibroblasts contribute to hypertrophic scarring","volume":"88","author":"Wang","year":"2008","journal-title":"Lab Invest."},{"key":"10.1016\/j.ejphar.2019.02.039_bib45","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1038\/jid.2014.84","article-title":"siRNA-targeting transforming growth factor-beta type I receptor reduces wound scarring and extracellular matrix deposition of scar tissue","volume":"134","author":"Wang","year":"2014","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.ejphar.2019.02.039_bib46","doi-asserted-by":"crossref","first-page":"7980","DOI":"10.12659\/MSM.910730","article-title":"Protective effect of anthocyanin on paraquat-induced apoptosis and epithelial-mesenchymal transition in alveolar type II cells","volume":"24","author":"Wang","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"10.1016\/j.ejphar.2019.02.039_bib47","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1126\/science.aav5542","article-title":"Cellular networks in wound healing","volume":"362","author":"Willenborg","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.ejphar.2019.02.039_bib48","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.1074\/jbc.M114.601872","article-title":"Salinomycin and other polyether ionophores are a new class of antiscarring agent","volume":"290","author":"Woeller","year":"2015","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2019.02.039_bib49","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/nm.2574","article-title":"Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling","volume":"18","author":"Wong","year":"2011","journal-title":"Nat. Med."},{"key":"10.1016\/j.ejphar.2019.02.039_bib50","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/nm.2807","article-title":"Mechanisms of fibrosis: therapeutic translation for fibrotic disease","volume":"18","author":"Wynn","year":"2012","journal-title":"Nat. Med."},{"key":"10.1016\/j.ejphar.2019.02.039_bib51","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1126\/science.1260972","article-title":"Innate immunity. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection","volume":"347","author":"Zhang","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.ejphar.2019.02.039_bib52","doi-asserted-by":"crossref","first-page":"4628","DOI":"10.1038\/srep04628","article-title":"Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanism","volume":"4","author":"Zhang","year":"2014","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejphar.2019.02.039_bib53","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11010-015-2644-3","article-title":"Galangin inhibits hypertrophic scar formation via ALK5\/Smad2\/3 signaling pathway","volume":"413","author":"Zhang","year":"2016","journal-title":"Mol. Cell Biochem."},{"key":"10.1016\/j.ejphar.2019.02.039_bib54","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/bjd.14108","article-title":"Baicalein attenuates hypertrophic scar formation via inhibition of the transforming growth factor-beta\/Smad2\/3 signalling pathway","volume":"174","author":"Zhang","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"10.1016\/j.ejphar.2019.02.039_bib55","doi-asserted-by":"crossref","first-page":"817","DOI":"10.2217\/rme.14.54","article-title":"Wound healing: an update","volume":"9","author":"Zielins","year":"2014","journal-title":"Regen. Med."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S001429991930144X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S001429991930144X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T22:26:30Z","timestamp":1757975190000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S001429991930144X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6]]},"references-count":55,"alternative-id":["S001429991930144X"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2019.02.039","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2019,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Dihydromyricetin attenuates hypertrophic scar formation by targeting activin receptor-like kinase 5","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2019.02.039","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}