{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:00:33Z","timestamp":1790359233111,"version":"4.1.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012175","name":"Zhejiang Traditional Chinese Medicine Administration","doi-asserted-by":"publisher","award":["2024ZL839"],"award-info":[{"award-number":["2024ZL839"]}],"id":[{"id":"10.13039\/501100012175","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Technology Project of Linping District, Hangzhou City","award":["LPWJ2023-02-27"],"award-info":[{"award-number":["LPWJ2023-02-27"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Fibrosis-associated wound remodeling is a feature of cutaneous wound healing characterized by fibroblast activation, extracellular matrix deposition, and profibrotic signaling. Ligustroside, a major iridoid glycoside derived from\n                    <jats:italic>Ligustrum lucidum<\/jats:italic>\n                    , has demonstrated antifibrotic activity in several organ systems, but its effects on cutaneous wound remodeling remain unclear. In this study, a full-thickness excisional wound model was established in female Sprague\u2013Dawley rats to investigate the effects of ligustroside on fibrosis-associated wound remodeling. Animals received ligustroside (5 or 10 mg\/kg) or vehicle control. Wound formation was evaluated using the Vancouver Scar Scale, histopathological staining, and analysis of fibrosis-related markers. Ligustroside treatment significantly reduced wound severity during the remodeling phase and improved dermal architecture, as evidenced by decreased dermal thickening, reduced inflammatory infiltration, and more organized collagen fibers. Molecular analyses showed that ligustroside markedly downregulated \u03b1-smooth muscle actin and transforming growth factor-\u03b21 expression, accompanied by showing a dose-responsive trend within the tested dose range. These findings indicate that ligustroside attenuates fibrosis-associated wound remodeling and suppresses fibrosis-related molecular responses, including TGF-\u03b21 expression, myofibroblast activation, and extracellular matrix accumulation. Collectively, these results suggest that ligustroside may represent a promising plant-derived candidate for antifibrotic wound modulation.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0358737","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:32:38Z","timestamp":1790357558000},"page":"e0358737","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ligustroside attenuates fibrosis-associated wound remodeling and suppresses fibrosis-related signaling in a rat excisional wound model"],"prefix":"10.1371","volume":"21","author":[{"given":"Kaymin","family":"Wu","sequence":"first","affiliation":[{"name":"Linping First People\u2019s Hospital","place":["Hang Zhou, Zhejiang, China"],"department":["Department of Plastic and Hand Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Chen","sequence":"additional","affiliation":[{"name":"Linping First People\u2019s Hospital","place":["Hang Zhou, Zhejiang, China"],"department":["Department of Plastic and Hand Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang Province People\u2019s Hospital","place":["Hang Zhou, Zhejiang, China"],"department":["Department of Basic Clinic Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4036-5843","authenticated-orcid":true,"given":"Youwu","family":"He","sequence":"additional","affiliation":[{"name":"Linping First People\u2019s Hospital","place":["Hang Zhou, Zhejiang, China"],"department":["Department of Plastic and Hand Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"issue":"2","key":"pone.0358737.ref001","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/ptr.2599","article-title":"Evaluation of wound healing activity of Lantana camara L. - a preclinical study","volume":"23","author":"BS Nayak","year":"2009","journal-title":"Phytother Res"},{"key":"pone.0358737.ref002","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":"GG Gauglitz","year":"2011","journal-title":"Mol Med"},{"issue":"2","key":"pone.0358737.ref003","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1089\/wound.2016.0696","article-title":"Cutaneous scarring: Basic science, current treatments, and future directions","volume":"7","author":"CD Marshall","year":"2018","journal-title":"Adv Wound Care (New Rochelle)"},{"issue":"1","key":"pone.0358737.ref004","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.clindermatol.2006.09.009","article-title":"Abnormal wound healing: Keloids","volume":"25","author":"DT Robles","year":"2007","journal-title":"Clin Dermatol"},{"issue":"2","key":"pone.0358737.ref005","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1097\/PRS.0b013e3181df715d","article-title":"Mechanical receptor-related mechanisms in scar management: A review and hypothesis","volume":"126","author":"C Yagmur","year":"2010","journal-title":"Plast Reconstr Surg"},{"issue":"2","key":"pone.0358737.ref006","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/wrr.12398","article-title":"Transforming growth factor beta (TGF-\u03b2) isoforms in wound healing and fibrosis","volume":"24","author":"MK Lichtman","year":"2016","journal-title":"Wound Repair Regen"},{"key":"pone.0358737.ref007","doi-asserted-by":"crossref","first-page":"19373341251381830","DOI":"10.1177\/19373341251381830","article-title":"Recent advances in astragaloside IV modulate immune response and skin cells promoting wound healing","author":"H Xiao","year":"2026","journal-title":"Tissue Eng Part B Rev"},{"issue":"18","key":"pone.0358737.ref008","doi-asserted-by":"crossref","first-page":"9838","DOI":"10.7150\/thno.117179","article-title":"Naturally derived hydrogel with antioxidant, angiogenesis and photothermal effect to accelerate infected diabetic wound healing and reduce scar formation","volume":"15","author":"M Yang","year":"2025","journal-title":"Theranostics"},{"key":"pone.0358737.ref009","doi-asserted-by":"crossref","first-page":"1330732","DOI":"10.3389\/fphar.2024.1330732","article-title":"A review of botany, phytochemistry, pharmacology, and applications of the herb with the homology of medicine and food: Ligustrum lucidum W.T. 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