{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T01:44:41Z","timestamp":1793324681238,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,25]],"date-time":"2022-12-25T00:00:00Z","timestamp":1671926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Mental Health Technology R&amp;D Project, Ministry of Health &amp; Welfare, Republic of Korea","award":["HP20C0171"],"award-info":[{"award-number":["HP20C0171"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>One of the most frequent comorbidities that develop in chronically ill or immobilized patients is pressure ulcers, also known as bed sores. Despite ischemia-reperfusion (I\/R)-induced skin lesion having been identified as a primary cause of pressure ulcers, wound management efforts have so far failed to significantly improve outcomes. Baicalin, or 5,6,7-trihydroxyflavone, is a type of flavonoid which has been shown to possess a variety of biological characteristics, including antioxidative and anti-inflammatory effects and protection of I\/R injury. In vitro wound scratch assay was first used to assess the function of baicalin in wound healing. We established a mouse model of advanced stage pressure ulcers with repeated cycles of I\/R pressure load. In this model, topically applied baicalin (100 mg\/mL) induced a significant increase in the wound healing process measured by wound area. Histological examination of the pressure ulcer mouse model showed faster granulation tissue formation and re-epithelization in the baicalin-treated group. Next, baicalin downregulated pro-inflammatory cytokines (IL-6 and IL-1\u03b2), while upregulating the anti-inflammatory IL-10. Additionally, baicalin induced an increase in several growth factors (VEGF, FGF-2, PDGF-\u03b2, and CTGF), promoting the wound healing process. Our results suggest that baicalin could serve as a promising agent for the treatment of pressures ulcers.<\/jats:p>","DOI":"10.3390\/ijms24010329","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T04:40:39Z","timestamp":1672116039000},"page":"329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Effect of Baicalin on Wound Healing in a Mouse Model of Pressure Ulcers"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1608-1402","authenticated-orcid":false,"given":"Eunbin","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoyoon","family":"Ham","sequence":"additional","affiliation":[{"name":"Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4347-560X","authenticated-orcid":false,"given":"Bok Ki","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Yonsei University, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Woo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Plastics and Reconstructive Surgery, Yongin Severance Hospital, Yongin 16995, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0047-5941","authenticated-orcid":false,"given":"Jihee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Scar Laser and Plastic Surgery Center, Yonsei Cancer Hospital, Seoul 03722, Republic of Korea"},{"name":"Department of Dermatology, Yongin Severance Hospital, Yongin 16995, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Scar Laser and Plastic Surgery Center, Yonsei Cancer Hospital, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,25]]},"reference":[{"key":"ref_1","first-page":"1186","article-title":"Pressure ulcers: Prevention, evaluation, and management","volume":"78","author":"Bluestein","year":"2008","journal-title":"Am. Fam. Physician"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jamda.2005.10.004","article-title":"Prevention and treatment of pressure ulcers","volume":"7","author":"Thomas","year":"2006","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms7575","article-title":"Impedance sensing device enables early detection of pressure ulcers in vivo","volume":"6","author":"Swisher","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2101292","DOI":"10.1002\/adhm.202101292","article-title":"Multifunctional Dressing for Wound Diagnosis and Rehabilitation","volume":"10","author":"Tang","year":"2021","journal-title":"Adv. Healthc. Mater."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"114555","DOI":"10.1016\/j.bios.2022.114555","article-title":"A fabric-based multifunctional sensor for the early detection of skin decubitus ulcers","volume":"215","author":"Kim","year":"2022","journal-title":"Biosens. Bioelectron."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/bjd.18154","article-title":"Nonblanchable erythema for predicting pressure ulcer development: A systematic review with an individual participant data meta-analysis","volume":"182","author":"Shi","year":"2020","journal-title":"Br. J. Derm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1524-475X.2009.00466.x","article-title":"Interactions between extracellular matrix and growth factors in wound healing","volume":"17","author":"Schultz","year":"2009","journal-title":"Wound Repair Regen."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/00000446-200212000-00022","article-title":"The Use of Papaya on Pressure Ulcers: A natural alternative","volume":"102","author":"Hewitt","year":"2002","journal-title":"AJN Am. J. Nurs."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s12291-020-00931-4","article-title":"Use of complementary and alternative medicine (CAM) and home remedies by COVID-19 patients: A telephonic survey","volume":"36","author":"Charan","year":"2021","journal-title":"Indian J. Clin. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1111\/exd.13679","article-title":"Topical application of quercetin improves wound healing in pressure ulcer lesions","volume":"27","author":"Yin","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ghanadian, M., Soltani, R., Homayouni, A., Khorvash, F., Jouabadi, S.M., and Abdollahzadeh, M. (2022). The Effect of Plantago major Hydroalcoholic Extract on the Healing of Diabetic Foot and Pressure Ulcers: A Randomized Open-Label Controlled Clinical Trial. Int. J. Low. Extrem. Wounds, 15347346211070723.","DOI":"10.1177\/15347346211070723"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"865059","DOI":"10.3389\/fbioe.2022.865059","article-title":"Multifunctional Arabinoxylan-functionalized-Graphene Oxide Based Composite Hydrogel for Skin Tissue Engineering","volume":"10","author":"Khan","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Khan, M.U.A., Iqbal, I., Ansari, M.N.M., Razak, S.I.A., Raza, M.A., Sajjad, A., Jabeen, F., Riduan Mohamad, M., and Jusoh, N. (2021). Development of antibacterial, degradable and ph-responsive chitosan\/guar gum\/polyvinyl alcohol blended hydrogels for wound dressing. Molecules, 26.","DOI":"10.3390\/molecules26195937"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/S1098-3015(10)61744-5","article-title":"Pdb21 a cost-utility analysis of insulin glargine (Lantus\u00ae) in the treatment of patients with type 1 diabetes","volume":"6","author":"Kristensen","year":"2003","journal-title":"Value Health"},{"key":"ref_15","first-page":"22063","article-title":"Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation, oxidative stress and P38MAPK pathway in rat","volume":"8","author":"Sun","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_16","first-page":"8958","article-title":"Baicalin induces apoptosis in hepatic cancer cells in vitro and suppresses tumor growth in vivo","volume":"8","author":"Yu","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ejmech.2017.03.004","article-title":"Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders","volume":"131","author":"Dinda","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105387","DOI":"10.1016\/j.phrs.2020.105387","article-title":"Baicalin mediated regulation of key signaling pathways in cancer","volume":"164","author":"Singh","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_19","first-page":"187","article-title":"The effect of topical quercetin loaded liposome on pressure ulcer healing in rats","volume":"8","author":"Bavarsad","year":"2021","journal-title":"Nanomed. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s00403-013-1385-y","article-title":"Fir honeydew honey flavonoids inhibit TNF-\u03b1-induced MMP-9 expression in human keratinocytes: A new action of honey in wound healing","volume":"305","author":"Majtan","year":"2013","journal-title":"Arch. Dermatol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1002\/ptr.5840","article-title":"Pharmacognosy, phytochemistry and pharmacological properties of Achillea millefolium L.: A review","volume":"31","author":"Ali","year":"2017","journal-title":"Phytother. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.jep.2006.03.011","article-title":"Safety and antiulcer efficacy studies of Achillea millefolium L. after chronic treatment in Wistar rats","volume":"107","author":"Cavalcanti","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Paudel, K.R., and Kim, D.-W. (2020). Microparticles-mediated vascular inflammation and its amelioration by antioxidant activity of baicalin. Antioxidants, 9.","DOI":"10.3390\/antiox9090890"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.cbi.2013.02.005","article-title":"Concentration-dependent inhibitory effects of baicalin on the metabolism of dextromethorphan, a dual probe of CYP2D and CYP3A, in rats","volume":"203","author":"Tian","year":"2013","journal-title":"Chem. -Biol. Interact."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e22893","DOI":"10.1002\/jbt.22893","article-title":"Baicalin regulates mRNA expression of VEGF-c, Ang-1\/Tie2, TGF-\u03b2 and Smad2\/3 to inhibit wound healing in streptozotocin-induced diabetic foot ulcer rats","volume":"35","author":"Mao","year":"2021","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"225","DOI":"10.4103\/0973-1296.186342","article-title":"Protective effect of baicalin against experimental colitis via suppression of oxidant stress and apoptosis","volume":"12","author":"Yao","year":"2016","journal-title":"Pharmacogn. Mag."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/0046-8177(91)90007-C","article-title":"Complexity of expression of intermediate filament proteins, including glial filament protein, in endometrial and ovarian adenocarcinomas","volume":"22","author":"Moll","year":"1991","journal-title":"Hum. Pathol."},{"key":"ref_28","first-page":"1667","article-title":"Keratin 17 expression as a marker for epithelial transformation in viral warts","volume":"143","author":"Proby","year":"1993","journal-title":"Am. J. Pathol."},{"key":"ref_29","first-page":"2079","article-title":"Baicalin increases hair follicle development by increasing canonical Wnt\/\u03b2-catenin signaling and activating dermal papillar cells in mice","volume":"41","author":"Xing","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1152\/physrev.2003.83.3.835","article-title":"Regulation of wound healing by growth factors and cytokines","volume":"83","author":"Werner","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/sj.jid.5700786","article-title":"Keratinocyte\u2013Fibroblast Interactions in Wound Healing","volume":"127","author":"Werner","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-82888-9","article-title":"bFGF and collagen matrix hydrogel attenuates burn wound inflammation through activation of ERK and TRK pathway","volume":"11","author":"Chakrabarti","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3389\/fbioe.2020.00345","article-title":"Sequential Delivery of Cryogel Released Growth Factors and Cytokines Accelerates Wound Healing and Improves Tissue Regeneration","volume":"8","author":"Jimi","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/jbm.a.10425","article-title":"In vivo leukocyte cytokine mRNA responses to biomaterials are dependent on surface chemistry","volume":"64A","author":"Brodbeck","year":"2003","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1084\/jem.20120690","article-title":"On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells","volume":"210","author":"Yona","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1111\/j.1346-8138.1992.tb03755.x","article-title":"The effects of basic fibroblast growth factor and doxorubicin on cultured human skin fibroblasts: Relevance to wound healing","volume":"19","author":"Sasaki","year":"1992","journal-title":"J. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1677\/erc.0.0070165","article-title":"Fibroblast growth factors, their receptors and signaling","volume":"7","author":"Powers","year":"2000","journal-title":"Endocr. -Relat. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.freeradbiomed.2020.08.015","article-title":"Angelica dahurica promoted angiogenesis and accelerated wound healing in db\/db mice via the HIF-1\u03b1\/PDGF-\u03b2 signaling pathway","volume":"160","author":"Guo","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chen, J.S., Longaker, M.T., and Gurtner, G.C. (2013). Murine models of human wound healing. Wound Regeneration and Repair, Springer.","DOI":"10.1007\/978-1-62703-505-7_15"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1111\/wrr.12751","article-title":"Noninvasive staging of pressure ulcers using photoacoustic imaging","volume":"27","author":"Hariri","year":"2019","journal-title":"Wound Repair Regen."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1111\/j.1524-475X.2009.00502.x","article-title":"A chronic pressure ulcer model in the nude mouse","volume":"17","author":"Wassermann","year":"2009","journal-title":"Wound Repair Regen."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/329\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:50:45Z","timestamp":1760147445000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/329"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,25]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24010329"],"URL":"https:\/\/doi.org\/10.3390\/ijms24010329","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,25]]}}}