{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:47:12Z","timestamp":1782103632597,"version":"3.54.5"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Histol"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1007\/s10735-026-10840-0","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T01:21:07Z","timestamp":1780708867000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Baicalin-loaded chitosan hydrogel accelerates diabetic foot ulcer healing by regulating MAPK1 expression"],"prefix":"10.1007","volume":"57","author":[{"given":"Xuepu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqiang","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xifan","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"issue":"2","key":"10840_CR2","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/s40257-019-00495-x","volume":"21","author":"PC Aldana","year":"2020","unstructured":"Aldana PC, Khachemoune A (2020) Diabetic foot ulcers: appraising standard of care and reviewing new trends in management. Am J Clin Dermatol 21(2):255\u2013264","journal-title":"AM J CLIN DERMATOL"},{"issue":"4","key":"10840_CR1","doi-asserted-by":"publisher","first-page":"272","DOI":"10.2174\/1567201816666190123121425","volume":"16","author":"ND Al-Jbour","year":"2019","unstructured":"Al-Jbour ND, Beg MD, Gimbun J, Alam A (2019) An overview of chitosan nanofibers and their applications in the drug delivery process. Curr drug deliv 16(4):272\u2013294","journal-title":"Curr drug deliv"},{"key":"10840_CR3","doi-asserted-by":"publisher","first-page":"123271","DOI":"10.1016\/j.ijbiomac.2023.123271","volume":"232","author":"Q Bai","year":"2023","unstructured":"Bai Q, Gao Q, Hu F, Zheng C, Chen W, Sun N et al (2023) Chitosan and hyaluronic-based hydrogels could promote the infected wound healing. Int J Biol Macromol 232:123271","journal-title":"INT J BIOL MACROMOL"},{"issue":"6","key":"10840_CR4","doi-asserted-by":"publisher","first-page":"e13807","DOI":"10.1111\/srt.13807","volume":"30","author":"J BangHong","year":"2024","unstructured":"BangHong J, YuKun W, Ao S, Tao S, PeiJun S, XuWen L et al (2024) Low-level laser activates Wnt\/beta-catenin signaling pathway-promoting hair follicle stem cell regeneration and wound healing: Upregulate the expression of key downstream gene Lef 1. Skin Res Technol 30(6):e13807","journal-title":"SKIN RES TECHNOL"},{"issue":"5","key":"10840_CR5","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.joim.2023.07.002","volume":"21","author":"Y Gong","year":"2023","unstructured":"Gong Y, Zhang C, Xiang X, Wang Z, Wang Y, Su Y et al (2023) Baicalin, silver titanate, Bletilla striata polysaccharide and carboxymethyl chitosan in a porous sponge dressing for burn wound healing. J Integr Med 21(5):487\u2013495","journal-title":"J Integr Med"},{"issue":"1","key":"10840_CR6","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.intimp.2010.10.003","volume":"11","author":"J Huh","year":"2011","unstructured":"Huh J, Nam D, Baek Y, Kang JW, Park D, Choi D et al (2011) Formononetin accelerates wound repair by the regulation of early growth response factor-1 transcription factor through the phosphorylation of the ERK and p38 MAPK pathways. Int Immunopharmacol 11(1):46\u201354","journal-title":"INT IMMUNOPHARMACOL"},{"key":"10840_CR7","doi-asserted-by":"crossref","unstructured":"Jagiello K, Uchanska O, Matyja K, Jackowski M, Wiatrak B, Kubasiewicz-Ross P et al (2023) Supporting the wound healing process-curcumin, resveratrol and baicalin in in vitro wound healing studies. Pharmaceuticals-Base 16(1):82","DOI":"10.3390\/ph16010082"},{"key":"10840_CR8","doi-asserted-by":"publisher","first-page":"tkae17","DOI":"10.1093\/burnst\/tkae017","volume":"12","author":"L Jin","year":"2024","unstructured":"Jin L, Zhou S, Zhao S, Long J, Huang Z, Zhou J et al (2024) Early short-term hypoxia promotes epidermal cell migration by activating the CCL2-ERK1\/2 pathway and epithelial-mesenchymal transition during wound healing. Burns Trauma 12:tkae17","journal-title":"BURNS TRAUMA"},{"issue":"1\/7","key":"10840_CR9","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1021\/acschemneuro.5c00769","volume":"2026","author":"V Karmakar","year":"2026","unstructured":"Karmakar V, Majie A, Ghosh A, Deb PK, Gorain B (2026) Decoding the neuroprotective intervention of angiotensin receptor blockers: a multimodal approach using in silico network pharmacology, molecular modeling, and in vivo validation of key markers. ACS Chem Neurosci 2026(1\/7):214\u2013230","journal-title":"ACS CHEM NEUROSCI"},{"issue":"1","key":"10840_CR10","doi-asserted-by":"publisher","first-page":"329","DOI":"10.3390\/ijms24010329","volume":"24","author":"E Kim","year":"2022","unstructured":"Kim E, Ham S, Jung BK, Park J, Kim J, Lee JH (2022) Effect of baicalin on wound healing in a mouse model of pressure ulcers. Int J Mol Sci 24(1):329","journal-title":"Int J Mol Sci"},{"key":"10840_CR11","doi-asserted-by":"publisher","first-page":"121952","DOI":"10.1016\/j.carbpol.2024.121952","volume":"333","author":"A Li","year":"2024","unstructured":"Li A, Ma B, Hua S, Ping R, Ding L, Tian B et al (2024a) Chitosan-based injectable hydrogel with multifunction for wound healing: a critical review. Carbohyd Polym 333:121952","journal-title":"CARBOHYD POLYM"},{"key":"10840_CR12","doi-asserted-by":"publisher","first-page":"1480626","DOI":"10.3389\/fphar.2024.1480626","volume":"15","author":"J Li","year":"2024","unstructured":"Li J, Zhuang Y, Fan G, Wang S, Yan E, Guo J et al (2024b) Impact of baicalin and components of Scutellaria baicalensis on renal fibrosis of diabetic kidney disease. Front Pharmacol 15:1480626","journal-title":"FRONT PHARMACOL"},{"issue":"16","key":"10840_CR13","doi-asserted-by":"publisher","first-page":"4242","DOI":"10.1039\/D4BM00349G","volume":"12","author":"A Majie","year":"2024","unstructured":"Majie A, Saha R, Sarkar A, Bhowmik R, Karmakar S, Sharma V et al (2024) A novel chitosan-PEG hydrogel embedded with in situ silver nanoparticles of Clerodendrum glandulosum Lindl. extract: evaluation of its in vivo diabetic wound healing properties using an image-guided machine learning model. Biomater Sci-UK 12(16):4242\u20134261","journal-title":"BIOMATER SCI-UK"},{"key":"10840_CR14","doi-asserted-by":"crossref","unstructured":"Majie A, Deb PK, Lim WM, Ghosh S, Gorain B (2026) Exploring molecular mechanism of thymoquinone via cMet and PDGFR for accelerated hemostasis: an approach through in silico, in vitro, and in vivo studies. Chem Biodivers 23(1):e03450","DOI":"10.1002\/cbdv.202503450"},{"issue":"11","key":"10840_CR15","doi-asserted-by":"publisher","first-page":"e22893","DOI":"10.1002\/jbt.22893","volume":"35","author":"X Mao","year":"2021","unstructured":"Mao X, Li Z, Li B, Wang H (2021) Baicalin regulates mRNA expression of VEGF-c, Ang-1\/Tie2, TGF-beta and Smad2\/3 to inhibit wound healing in streptozotocin-induced diabetic foot ulcer rats. J Biochem Mol Toxic 35(11):e22893","journal-title":"J BIOCHEM MOL TOXIC"},{"key":"10840_CR16","doi-asserted-by":"publisher","first-page":"123407","DOI":"10.1016\/j.carbpol.2025.123407","volume":"356","author":"Y Mao","year":"2025","unstructured":"Mao Y, Zhao B, Xu L, Wang Y, Qiu X, Sun Y et al (2025) Protein-polysaccharide based nanogel\/hydrogel composite with controlled continuous delivery of drug for enhanced wound healing. CARBOHYD POLYM 356:123407","journal-title":"CARBOHYD POLYM"},{"issue":"15","key":"10840_CR17","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.2174\/1389450121666200711172536","volume":"21","author":"SM Matalqah","year":"2020","unstructured":"Matalqah SM, Aiedeh K, Mhaidat NM, Alzoubi KH, Bustanji Y, Hamad I (2020) Chitosan nanoparticles as a novel drug delivery system: a review article. Curr Drug Targets 21(15):1613\u20131624","journal-title":"CURR DRUG TARGETS"},{"issue":"1","key":"10840_CR18","doi-asserted-by":"publisher","first-page":"209","DOI":"10.2337\/dci22-0043","volume":"46","author":"K McDermott","year":"2023","unstructured":"McDermott K, Fang M, Boulton AJM, Selvin E, Hicks CW (2023) Etiology, epidemiology, and disparities in the burden of diabetic foot ulcers. Diabetes Care 46(1):209\u2013221","journal-title":"Diabetes Care"},{"issue":"17","key":"10840_CR19","doi-asserted-by":"publisher","first-page":"3464","DOI":"10.3390\/molecules30173464","volume":"30","author":"X Meng","year":"2025","unstructured":"Meng X, Ning C, Kang M, Wang X, Yu Z, Hao X et al (2025) Baicalin: natural sources, extraction techniques, and therapeutic applications against bacterial infections. Molecules 30(17):3464","journal-title":"Molecules"},{"key":"10840_CR20","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.jconrel.2020.06.012","volume":"326","author":"S Peers","year":"2020","unstructured":"Peers S, Montembault A, Ladaviere C (2020) Chitosan hydrogels for sustained drug delivery. J Control Release 326:150\u2013163","journal-title":"J CONTROL RELEASE"},{"key":"10840_CR21","doi-asserted-by":"publisher","first-page":"116571","DOI":"10.1016\/j.biopha.2024.116571","volume":"175","author":"W Qin","year":"2024","unstructured":"Qin W, Shang Q, Shen G, Li B, Zhang P, Zhang Y et al (2024) Restoring bone-fat equilibrium: Baicalin\u2019s impact on P38 MAPK pathway for treating diabetic osteoporosis. Biomed Pharmacother 175:116571","journal-title":"BIOMED PHARMACOTHER"},{"key":"10840_CR22","doi-asserted-by":"crossref","unstructured":"Roy K, Gorain B (2025) Targeting AMPK signaling in diabetic wounds facilitates the healing process. Drug Discov Today 30:104511","DOI":"10.1016\/j.drudis.2025.104511"},{"key":"10840_CR23","doi-asserted-by":"crossref","unstructured":"Roy K, Majie A, Jha B, Chatterjee A, Lim WM, Gorain B (2025) Comparative physicochemical, microbiological, pharmacological, and toxicological evaluations of different varieties of honey targeting wound repairment. Biocatal Agric Biotech 65:103544","DOI":"10.1016\/j.bcab.2025.103544"},{"key":"10840_CR24","doi-asserted-by":"publisher","first-page":"135803","DOI":"10.1016\/j.ijbiomac.2024.135803","volume":"280","author":"A Salahuddin","year":"2024","unstructured":"Salahuddin A, Ashraf A, Ahmad K, Hou H (2024) Recent advances in chitosan-based smart hydrogel for drug delivery systems. Int J Biol Macromol 280:135803","journal-title":"INT J BIOL MACROMOL"},{"key":"10840_CR25","doi-asserted-by":"publisher","first-page":"123902","DOI":"10.1016\/j.ijbiomac.2023.123902","volume":"235","author":"B Tian","year":"2023","unstructured":"Tian B, Liu J (2023) Smart stimuli-responsive chitosan hydrogel for drug delivery: a review. Int J Biol Macromol 235:123902","journal-title":"INT J BIOL MACROMOL"},{"key":"10840_CR26","doi-asserted-by":"publisher","first-page":"100146","DOI":"10.1016\/j.tcsw.2025.100146","volume":"14","author":"J Wagener","year":"2025","unstructured":"Wagener J, Wang X, Becker KL, Aimanianda V, Valsecchi I, Gresnigt MS et al (2025) Immunomodulatory function of chitosan is dependent on complement receptor 3. Cell Surf 14:100146","journal-title":"Cell Surf"},{"key":"10840_CR28","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.diabres.2019.02.024","volume":"150","author":"T Wang","year":"2019","unstructured":"Wang T, Li X, Fan L, Chen B, Liu J, Tao Y et al (2019) Negative pressure wound therapy promoted wound healing by suppressing inflammation via down-regulating MAPK-JNK signaling pathway in diabetic foot patients. Diabetes Res Clin PR 150:81\u201389","journal-title":"DIABETES RES CLIN PR"},{"key":"10840_CR27","doi-asserted-by":"publisher","first-page":"110487","DOI":"10.1016\/j.exer.2025.110487","volume":"258","author":"R Wang","year":"2025","unstructured":"Wang R, Dong C, Chen Y, Chen C, Zhao X, Han X et al (2025) Baicalin ameliorates inflammation response in diabetic dry eye models through the inhibition of the PERK\/TXNIP\/NLRP3 pathway. Exp Eye Res 258:110487","journal-title":"EXP EYE RES"},{"issue":"4","key":"10840_CR29","doi-asserted-by":"publisher","first-page":"e70157","DOI":"10.1111\/iwj.70157","volume":"22","author":"J Wernecke","year":"2025","unstructured":"Wernecke J, Wernecke M, Ebenau O, Spruth B, Kramer M, Vogelmann T et al (2025) Epidemiology and the medical burden of diabetic foot ulcers especially in patients with infection-a population-based analysis From Germany. Int Wound J 22(4):e70157","journal-title":"INT WOUND J"},{"issue":"3","key":"10840_CR30","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1177\/1947601911407328","volume":"2","author":"I Wortzel","year":"2011","unstructured":"Wortzel I, Seger R (2011) The ERK Cascade: distinct functions within various subcellular organelles. Genes Cancer 2(3):195\u2013209","journal-title":"Genes Cancer"},{"issue":"5","key":"10840_CR31","doi-asserted-by":"publisher","first-page":"e2300399","DOI":"10.1002\/mabi.202300399","volume":"24","author":"Y Xia","year":"2024","unstructured":"Xia Y, Ma Z, Wu X, Wei H, Zhang H, Li G et al (2024) Advances in stimuli-responsive chitosan hydrogels for drug delivery systems. Macromol Biosci 24(5):e2300399","journal-title":"MACROMOL BIOSCI"},{"issue":"7","key":"10840_CR32","doi-asserted-by":"publisher","first-page":"4195","DOI":"10.1021\/acsbiomaterials.4c00470","volume":"10","author":"X Xiao","year":"2024","unstructured":"Xiao X, Zhao F, DuBois DB, Liu Q, Zhang YL, Yao Q et al (2024) Nanozymes for the therapeutic treatment of diabetic foot ulcers. ACS Biomater Sci Eng 10(7):4195\u20134226","journal-title":"ACS BIOMATER SCI ENG"},{"issue":"30","key":"10840_CR33","doi-asserted-by":"publisher","first-page":"e2401490","DOI":"10.1002\/adhm.202401490","volume":"13","author":"J Xu","year":"2024","unstructured":"Xu J, Chang L, Xiong Y, Peng Q (2024) Chitosan-based hydrogels as antibacterial\/antioxidant\/anti\u2010inflammation multifunctional dressings for chronic wound healing. Adv Healthc Mater 13(30):e2401490","journal-title":"ADV HEALTHC MATER"},{"issue":"9","key":"10840_CR34","doi-asserted-by":"publisher","first-page":"e108182","DOI":"10.1371\/journal.pone.0108182","volume":"9","author":"YH Xuan","year":"2014","unstructured":"Xuan YH, Huang BB, Tian HS, Chi LS, Duan YM, Wang X et al (2014) High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation. PLoS ONE 9(9):e108182","journal-title":"PLoS ONE"},{"issue":"Pt 2","key":"10840_CR35","doi-asserted-by":"publisher","first-page":"135939","DOI":"10.1016\/j.ijbiomac.2024.135939","volume":"280","author":"Y Yang","year":"2024","unstructured":"Yang Y, Ma Y, Wang H, Li C, Li C, Zhang R et al (2024) Chitosan-based hydrogel dressings with antibacterial and antioxidant for wound healing. Int J Biol Macromol 280(Pt 2):135939","journal-title":"INT J BIOL MACROMOL"},{"issue":"6","key":"10840_CR36","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/s41374-018-0025-8","volume":"98","author":"X Yuan","year":"2018","unstructured":"Yuan X, Han L, Fu P, Zeng H, Lv C, Chang W et al (2018) Cinnamaldehyde accelerates wound healing by promoting angiogenesis via up-regulation of PI3K and MAPK signaling pathways. Lab Invest 98(6):783\u2013798","journal-title":"LAB INVEST"},{"issue":"1","key":"10840_CR37","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1042\/CBI20090016","volume":"34","author":"N Zhang","year":"2010","unstructured":"Zhang N, Cai W, Yin G, Nagel DJ, Berk BC (2010) GIT1 is a novel MEK1\u2013ERK1\/2 scaffold that localizes to focal adhesions. Cell Biol Int 34(1):41\u201347","journal-title":"CELL BIOL INT"},{"issue":"28","key":"10840_CR38","doi-asserted-by":"publisher","first-page":"31737","DOI":"10.1021\/acsami.2c08593","volume":"14","author":"X Zhang","year":"2022","unstructured":"Zhang X, Feng J, Feng W, Xu B, Zhang K, Ma G et al (2022) Glycosaminoglycan-based hydrogel delivery system regulates the wound microenvironment to rescue chronic wound healing. ACS Appl Mater Inter 14(28):31737\u201331750","journal-title":"ACS APPL MATER INTER"},{"key":"10840_CR39","doi-asserted-by":"crossref","unstructured":"Zhang K, Zhu J, Sun W, Zhang Y, Li W, Wang Y et al (2025) Antibacterial betaine modified chitosan-based hydrogel with angiogenic property for photothermal enhanced diabetic wound repairing. Carbohyd Polym 349(Pt B):123033.","DOI":"10.1016\/j.carbpol.2024.123033"},{"key":"10840_CR40","doi-asserted-by":"publisher","first-page":"116579","DOI":"10.1016\/j.biopha.2024.116579","volume":"174","author":"Y Zheng","year":"2024","unstructured":"Zheng Y, Wang C, Liu W, Chen J, Sun Y, Chang D et al (2024) Upregulation of Nrf2 signaling: A key molecular mechanism of Baicalin\u2019s neuroprotective action against diabetes-induced cognitive impairment. Biomed Pharmacother 174:116579","journal-title":"BIOMED PHARMACOTHER"}],"container-title":["Journal of Molecular Histology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10735-026-10840-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10735-026-10840-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10735-026-10840-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T03:48:55Z","timestamp":1782100135000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10735-026-10840-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10840"],"URL":"https:\/\/doi.org\/10.1007\/s10735-026-10840-0","relation":{},"ISSN":["1567-2379","1567-2387"],"issn-type":[{"value":"1567-2379","type":"print"},{"value":"1567-2387","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"28 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The animal study was approved by the Ethics Committee of Jinzhou Medical University. All animal experiments complied with the ARRIVE guidelines. All methods were carried out in accordance with relevant guidelines and regulations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"184"}}