{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:46:52Z","timestamp":1792273612009,"version":"4.4.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"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":[[2026,10]]},"DOI":"10.1007\/s10735-026-10978-x","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:17:55Z","timestamp":1790392675000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Yohimbine attenuates bleomycin-induced skin fibrosis by modulating the PI3K\/Akt-MAPK signaling: an integrated network pharmacology and in vivo study"],"prefix":"10.1007","volume":"57","author":[{"given":"Abhisheik","family":"Eedara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeyasankari","family":"S","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh","family":"Chandra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muralidharan","family":"Kathirvel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-737X","authenticated-orcid":false,"given":"Sai Balaji","family":"Andugulapati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,26]]},"reference":[{"key":"10978_CR1","doi-asserted-by":"publisher","first-page":"101252","DOI":"10.1016\/j.mam.2024.101252","volume":"96","author":"D Abraham","year":"2024","unstructured":"Abraham D, Lescoat A, Stratton R (2024) Emerging diagnostic and therapeutic challenges for skin fibrosis in systemic sclerosis. Mol Aspects Med 96:101252. https:\/\/doi.org\/10.1016\/j.mam.2024.101252","journal-title":"Mol Aspects Med"},{"key":"10978_CR2","doi-asserted-by":"publisher","first-page":"153298","DOI":"10.1016\/j.phymed.2020.153298","volume":"78","author":"SB Andugulapati","year":"2020","unstructured":"Andugulapati SB, Gourishetti K, Tirunavalli SK et al (2020) Biochanin-A ameliorates pulmonary fibrosis by suppressing the TGF-\u03b2 mediated EMT, myofibroblasts differentiation and collagen deposition in in vitro and in vivo systems. Phytomedicine 78:153298. https:\/\/doi.org\/10.1016\/j.phymed.2020.153298","journal-title":"Phytomedicine"},{"key":"10978_CR3","doi-asserted-by":"publisher","first-page":"4004","DOI":"10.3390\/ijms24044004","volume":"24","author":"SA Antar","year":"2023","unstructured":"Antar SA, Ashour NA, Marawan ME, Al-Karmalawy AA (2023) Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation. IJMS 24:4004. https:\/\/doi.org\/10.3390\/ijms24044004","journal-title":"IJMS"},{"key":"10978_CR4","doi-asserted-by":"publisher","first-page":"3121","DOI":"10.1093\/rheumatology\/keab190","volume":"60","author":"M Bairkdar","year":"2021","unstructured":"Bairkdar M, Rossides M, Westerlind H et al (2021) Incidence and prevalence of systemic sclerosis globally: a comprehensive systematic review and meta-analysis. Rheumatology 60:3121\u20133133. https:\/\/doi.org\/10.1093\/rheumatology\/keab190","journal-title":"Rheumatology"},{"key":"10978_CR5","doi-asserted-by":"publisher","first-page":"5603","DOI":"10.1038\/sj.emboj.7601421","volume":"25","author":"A Boutet","year":"2006","unstructured":"Boutet A, De Frutos CA, Maxwell PH et al (2006) Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidney. EMBO J 25:5603\u20135613. https:\/\/doi.org\/10.1038\/sj.emboj.7601421","journal-title":"EMBO J"},{"key":"10978_CR6","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.retram.2016.06.003","volume":"64","author":"NN Do","year":"2016","unstructured":"Do NN, Eming SA (2016) Skin fibrosis: Models and mechanisms. Curr Res Translational Med 64:185\u2013193. https:\/\/doi.org\/10.1016\/j.retram.2016.06.003","journal-title":"Curr Res Translational Med"},{"key":"10978_CR7","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/j.ajpath.2023.01.008","volume":"193","author":"DM Dolivo","year":"2023","unstructured":"Dolivo DM, Sun LS, Rodrigues AE et al (2023) Epidermal Potentiation of Dermal Fibrosis. Am J Pathol 193:510\u2013519. https:\/\/doi.org\/10.1016\/j.ajpath.2023.01.008","journal-title":"Am J Pathol"},{"issue":"200008","key":"10978_CR8","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.1002\/1529-0131","volume":"43","author":"NA Flavahan","year":"2000","unstructured":"Flavahan NA, Flavahan S, Liu Q et al (2000) Increased alpha2-adrenergic constriction of isolated arterioles in diffuse scleroderma. Arthritis Rheum 43(200008):1886\u20131890. https:\/\/doi.org\/10.1002\/1529-0131. )43:8%3C1886::AID-ANR27%3E3.0.CO;2-S","journal-title":"Arthritis Rheum"},{"key":"10978_CR9","doi-asserted-by":"publisher","first-page":"8394","DOI":"10.3390\/ijms26178394","volume":"26","author":"K Grafanaki","year":"2025","unstructured":"Grafanaki K, Maniatis A, Sotiropoulou V et al (2025) Fibrotic Disease of the Skin and Lung: Shared Pathways, Environmental Drivers, and Therapeutic Opportunities in a Changing Climate. IJMS 26:8394. https:\/\/doi.org\/10.3390\/ijms26178394","journal-title":"IJMS"},{"key":"10978_CR10","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1074\/jbc.M306248200","volume":"279","author":"JC Horowitz","year":"2004","unstructured":"Horowitz JC, Lee DY, Waghray M et al (2004) Activation of the Pro-survival Phosphatidylinositol 3-Kinase\/AKT Pathway by Transforming Growth Factor-\u03b21 in Mesenchymal Cells Is Mediated by p38 MAPK-dependent Induction of an Autocrine Growth Factor. J Biol Chem 279:1359\u20131367. https:\/\/doi.org\/10.1074\/jbc.M306248200","journal-title":"J Biol Chem"},{"key":"10978_CR11","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1136\/annrheumdis-2014-207109","volume":"75","author":"J Huang","year":"2016","unstructured":"Huang J, Beyer C, Palumbo-Zerr K et al (2016a) Nintedanib inhibits fibroblast activation and ameliorates fibrosis in preclinical models of systemic sclerosis. Ann Rheum Dis 75:883\u2013890. https:\/\/doi.org\/10.1136\/annrheumdis-2014-207109","journal-title":"Ann Rheum Dis"},{"key":"10978_CR12","doi-asserted-by":"publisher","first-page":"R161","DOI":"10.1186\/ar2068","volume":"8","author":"T Iwasaki","year":"2006","unstructured":"Iwasaki T, Imado T, Kitano S, Sano H (2006) Hepatocyte growth factor ameliorates dermal sclerosis in the tight-skin mouse model of scleroderma. Arthritis Res Ther 8:R161. https:\/\/doi.org\/10.1186\/ar2068","journal-title":"Arthritis Res Ther"},{"key":"10978_CR13","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/j.1346-8138.2009.00738.x","volume":"37","author":"M Jinnin","year":"2010","unstructured":"Jinnin M (2010) Mechanisms of skin fibrosis in systemic sclerosis. J Dermatol 37:11\u201325. https:\/\/doi.org\/10.1111\/j.1346-8138.2009.00738.x","journal-title":"J Dermatol"},{"key":"10978_CR14","doi-asserted-by":"publisher","first-page":"116613","DOI":"10.1016\/j.bcp.2024.116613","volume":"230","author":"V Kambhampati","year":"2024","unstructured":"Kambhampati V, Eedara A, Andugulapati SB (2024a) Yohimbine treatment improves pulmonary fibrosis by attenuating the inflammation and oxidative stress via modulating the MAPK pathway. Biochem Pharmacol 230:116613. https:\/\/doi.org\/10.1016\/j.bcp.2024.116613","journal-title":"Biochem Pharmacol"},{"key":"10978_CR15","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.3390\/jcm11092299","volume":"11","author":"V Kowalska-K\u0119pczy\u0144ska","year":"2022","unstructured":"Kowalska-K\u0119pczy\u0144ska A (2022) Systemic scleroderma\u2014definition, clinical picture and laboratory diagnostics. JCM 11:2299.https:\/\/doi.org\/10.3390\/jcm11092299.","journal-title":"JCM"},{"key":"10978_CR16","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1165\/rcmb.2013-0152OC","volume":"49","author":"HG Leach","year":"2013","unstructured":"Leach HG, Chrobak I, Han R, Trojanowska M (2013) Endothelial cells recruit macrophages and contribute to a fibrotic milieu in bleomycin lung injury. Am J Respir Cell Mol Biol 49:1093\u20131101. https:\/\/doi.org\/10.1165\/rcmb.2013-0152OC","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10978_CR17","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1038\/mt.2013.146","volume":"21","author":"S-W Lee","year":"2013","unstructured":"Lee S-W, Won J-Y, Kim WJ et al (2013) Snail as a Potential Target Molecule in Cardiac Fibrosis: Paracrine Action of Endothelial Cells on Fibroblasts Through Snail and CTGF Axis. Mol Ther 21:1767\u20131777. https:\/\/doi.org\/10.1038\/mt.2013.146","journal-title":"Mol Ther"},{"key":"10978_CR18","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41421-025-00783-3","volume":"11","author":"T Li","year":"2025","unstructured":"Li T, Wang G, Zhao H et al (2025) Estrogen receptor 1 signaling in hepatic stellate cells designates resistance to liver fibrosis. Cell Discov 11:37. https:\/\/doi.org\/10.1038\/s41421-025-00783-3","journal-title":"Cell Discov"},{"key":"10978_CR19","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1002\/art.30074","volume":"63","author":"S Liu","year":"2011","unstructured":"Liu S, Shi-wen X, Abraham DJ, Leask A (2011) CCN2 is required for bleomycin\u2010induced skin fibrosis in mice. Arthr Rhuem 63:239\u2013246. https:\/\/doi.org\/10.1002\/art.30074","journal-title":"Arthr Rhuem"},{"key":"10978_CR20","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.jgg.2021.09.009","volume":"49","author":"S Lu","year":"2022","unstructured":"Lu S, Wang Y, Liu J (2022) Tumor necrosis factor-\u03b1 signaling in nonalcoholic steatohepatitis and targeted therapies. J Genet Genomics 49:269\u2013278. https:\/\/doi.org\/10.1016\/j.jgg.2021.09.009","journal-title":"J Genet Genomics"},{"key":"10978_CR21","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1054\/mehy.2001.1459","volume":"58","author":"MF McCarty","year":"2002","unstructured":"McCarty MF (2002) Pre-exercise administration of yohimbine may enhance the efficacy of exercise training as a fat loss strategy by boosting lipolysis. Med Hypotheses 58:491\u2013495. https:\/\/doi.org\/10.1054\/mehy.2001.1459","journal-title":"Med Hypotheses"},{"key":"10978_CR22","doi-asserted-by":"publisher","first-page":"721","DOI":"10.3109\/01902149809099592","volume":"24","author":"LA Ortiz","year":"1998","unstructured":"Ortiz LA, Lasky J, Hamilton RF et al (1998) Expression of TNF and the Necessity of TNF Receptors in Bleomycin-Induced Lung Injury in Mice. Exp Lung Res 24:721\u2013743. https:\/\/doi.org\/10.3109\/01902149809099592","journal-title":"Exp Lung Res"},{"key":"10978_CR23","doi-asserted-by":"publisher","first-page":"112085","DOI":"10.1016\/j.exger.2023.112085","volume":"172","author":"J Peng","year":"2023","unstructured":"Peng J, Xiao X, Li S et al (2023) Aspirin alleviates pulmonary fibrosis through PI3K\/AKT\/mTOR-mediated autophagy pathway. Exp Gerontol 172:112085. https:\/\/doi.org\/10.1016\/j.exger.2023.112085","journal-title":"Exp Gerontol"},{"key":"10978_CR24","doi-asserted-by":"publisher","first-page":"175820","DOI":"10.1016\/j.ejphar.2023.175820","volume":"953","author":"TB Shaikh","year":"2023","unstructured":"Shaikh TB, Kuncha M, Andugulapati SB, Sistla R (2023) Dehydrozingerone alleviates pulmonary fibrosis via inhibition of inflammation and epithelial-mesenchymal transition by regulating the Wnt\/\u03b2-catenin pathway. Eur J Pharmacol 953:175820. https:\/\/doi.org\/10.1016\/j.ejphar.2023.175820","journal-title":"Eur J Pharmacol"},{"key":"10978_CR25","doi-asserted-by":"publisher","first-page":"155182","DOI":"10.1016\/j.phymed.2023.155182","volume":"123","author":"N Sharma","year":"2024","unstructured":"Sharma N, Sistla R, Andugulapati SB (2024) Yohimbine ameliorates liver inflammation and fibrosis by regulating oxidative stress and Wnt\/\u03b2-catenin pathway. Phytomedicine 123:155182. https:\/\/doi.org\/10.1016\/j.phymed.2023.155182","journal-title":"Phytomedicine"},{"key":"10978_CR26","doi-asserted-by":"publisher","first-page":"121747","DOI":"10.1016\/j.jep.2026.121747","volume":"367","author":"Y Shi","year":"2026","unstructured":"Shi Y, Zhang Y, Liu D et al (2026) Diosgenin alleviates hepatic fibrosis via PI3K\/Akt\/mTOR mediated fatty acid metabolic reprogramming and NF-\u03baB activation. J Ethnopharmacol 367:121747. https:\/\/doi.org\/10.1016\/j.jep.2026.121747","journal-title":"J Ethnopharmacol"},{"key":"10978_CR27","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1002\/art.23436","volume":"58","author":"C Skhirtladze","year":"2008","unstructured":"Skhirtladze C, Distler O, Dees C et al (2008) Src kinases in systemic sclerosis: Central roles in fibroblast activation and in skin fibrosis. Arthr Rhuem 58:1475\u20131484. https:\/\/doi.org\/10.1002\/art.23436","journal-title":"Arthr Rhuem"},{"key":"10978_CR28","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/s11926-009-0080-7","volume":"12","author":"GP Smith","year":"2010","unstructured":"Smith GP, Chan ESL (2010) Molecular Pathogenesis of Skin Fibrosis: Insight from Animal Models. Curr Rheumatol Rep 12:26\u201333. https:\/\/doi.org\/10.1007\/s11926-009-0080-7","journal-title":"Curr Rheumatol Rep"},{"key":"10978_CR29","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1007\/s10753-024-01985-9","volume":"47","author":"A Veeram","year":"2024","unstructured":"Veeram A, Shaikh TB, Kaur R et al (2024) Yohimbine Treatment Alleviates Cardiac Inflammation\/Injury and Improves Cardiac Hemodynamics by Modulating Pro-Inflammatory and Oxidative Stress Indicators. Inflammation 47:1423\u20131443. https:\/\/doi.org\/10.1007\/s10753-024-01985-9","journal-title":"Inflammation"},{"key":"10978_CR30","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.3390\/antiox11091685","volume":"11","author":"Y Wang","year":"2022","unstructured":"Wang Y, Wei J, Deng H et al (2022) The Role of Nrf2 in Pulmonary Fibrosis: Molecular Mechanisms and Treatment Approaches. Antioxidants 11:1685. https:\/\/doi.org\/10.3390\/antiox11091685","journal-title":"Antioxidants"},{"key":"10978_CR31","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1165\/rcmb.2012-0097OC","volume":"47","author":"M Wygrecka","year":"2012","unstructured":"Wygrecka M, Zakrzewicz D, Taborski B et al (2012) TGF-\u03b21 Induces Tissue Factor Expression in Human Lung Fibroblasts in a PI3K\/JNK\/Akt-Dependent and AP-1\u2013Dependent Manner. Am J Respir Cell Mol Biol 47:614\u2013627. https:\/\/doi.org\/10.1165\/rcmb.2012-0097OC","journal-title":"Am J Respir Cell Mol Biol"},{"key":"10978_CR32","doi-asserted-by":"publisher","first-page":"26000308","DOI":"10.1016\/j.jid.2026.01.009","volume":"0022202X","author":"F Xie","year":"2026","unstructured":"Xie F, Xie Y, Liu J (2026) Botulinum neurotoxin type A1 alleviates bleomycin-induced skin fibrosis by inhibiting phosphatidylinositol 3-kinase\u2013protein kinase B (PI3K-Akt) pathway and associated cell cycle and proliferation. J Invest Dermatology S 0022202X:26000308. https:\/\/doi.org\/10.1016\/j.jid.2026.01.009","journal-title":"J Invest Dermatology S"},{"key":"10978_CR34","doi-asserted-by":"publisher","first-page":"5699","DOI":"10.3892\/mmr.2016.5960","volume":"14","author":"X-L Zhang","year":"2016","unstructured":"Zhang X-L, Xing R-G, Chen L et al (2016) PI3K\/Akt signaling is involved in the pathogenesis of bleomycin-induced pulmonary fibrosis via regulation of epithelial-mesenchymal transition. Mol Med Rep 14:5699\u20135706. https:\/\/doi.org\/10.3892\/mmr.2016.5960","journal-title":"Mol Med Rep"},{"key":"10978_CR35","doi-asserted-by":"publisher","first-page":"116413","DOI":"10.1016\/j.biopha.2024.116413","volume":"173","author":"Z Zhang","year":"2024","unstructured":"Zhang Z, Yang Z, Wang S et al (2024) Targeting MAPK-ERK\/JNK pathway: A potential intervention mechanism of myocardial fibrosis in heart failure. Biomed Pharmacother 173:116413. https:\/\/doi.org\/10.1016\/j.biopha.2024.116413","journal-title":"Biomed Pharmacother"},{"key":"10978_CR33","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12964-025-02210-2","volume":"23","author":"X Zhang","year":"2025","unstructured":"Zhang X, Sun J, Guo J et al (2025) Inhibition of adenosine\/A2A receptor signaling suppresses dermal fibrosis by enhancing fatty acid oxidation. Cell Commun Signal 23:206. https:\/\/doi.org\/10.1186\/s12964-025-02210-2","journal-title":"Cell Commun Signal"},{"key":"10978_CR36","doi-asserted-by":"publisher","first-page":"24476","DOI":"10.3390\/ijms141224476","volume":"14","author":"B Zhu","year":"2013","unstructured":"Zhu B, Ma A-Q, Yang L, Dang X-M (2013) Atorvastatin Attenuates Bleomycin-Induced Pulmonary Fibrosis via Suppressing iNOS Expression and the CTGF (CCN2)\/ERK Signaling Pathway. IJMS 14:24476\u201324491. https:\/\/doi.org\/10.3390\/ijms141224476","journal-title":"IJMS"}],"container-title":["Journal of Molecular Histology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10735-026-10978-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10735-026-10978-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10735-026-10978-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:19:28Z","timestamp":1792271968000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10735-026-10978-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,26]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10978"],"URL":"https:\/\/doi.org\/10.1007\/s10735-026-10978-x","relation":{},"ISSN":["1567-2379","1567-2387"],"issn-type":[{"value":"1567-2379","type":"print"},{"value":"1567-2387","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,26]]},"assertion":[{"value":"10 July 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"320"}}