{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:39:49Z","timestamp":1786981189647,"version":"build-2736575974"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T00:00:00Z","timestamp":1536883200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100010803","name":"Department of Biotechnology","doi-asserted-by":"crossref","award":["MAP\/2015\/58"],"award-info":[{"award-number":["MAP\/2015\/58"]}],"id":[{"id":"10.13039\/501100010803","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010803","name":"Department of Biotechnology","doi-asserted-by":"crossref","award":["\/IC-2\/Indo-Brazil\/2016-19\/01"],"award-info":[{"award-number":["\/IC-2\/Indo-Brazil\/2016-19\/01"]}],"id":[{"id":"10.13039\/501100010803","id-type":"DOI","asserted-by":"crossref"}]},{"name":"DST-Science and Engineering Board","award":["ECR\/2016\/000007"],"award-info":[{"award-number":["ECR\/2016\/000007"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflammopharmacol"],"published-print":{"date-parts":[[2019,2]]},"DOI":"10.1007\/s10787-018-0527-4","type":"journal-article","created":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T00:14:16Z","timestamp":1536884056000},"page":"139-149","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Nimbolide ameliorates fibrosis and inflammation in experimental murine model of bleomycin-induced scleroderma"],"prefix":"10.1007","volume":"27","author":[{"given":"Snehalatha","family":"Diddi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swarna","family":"Bale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gauthami","family":"Pulivendala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5904-3134","authenticated-orcid":false,"given":"Chandraiah","family":"Godugu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,9,14]]},"reference":[{"key":"527_CR1","doi-asserted-by":"crossref","unstructured":"Alzohairy MA (2016). Therapeutics role of Azadirachta indica (Neem) and their active constituents in diseases prevention and treatment. Evid Based Complement Altern Med 2016","DOI":"10.1155\/2016\/7382506"},{"key":"527_CR2","doi-asserted-by":"publisher","first-page":"643","DOI":"10.4103\/0253-7613.194859","volume":"48","author":"S Bale","year":"2016","unstructured":"Bale S, Sunkoju M, Reddy SS, Swamy V, Godugu C (2016) Oropharyngeal aspiration of bleomycin: an alternative experimental model of pulmonary fibrosis developed in Swiss mice. Indian J Pharmacol 48:643","journal-title":"Indian J Pharmacol"},{"key":"527_CR3","doi-asserted-by":"publisher","first-page":"248","DOI":"10.3389\/fphar.2018.00248","volume":"9","author":"S Bale","year":"2018","unstructured":"Bale S, Venkatesh P, Sunkoju M, Godugu C (2018) An adaptogen: withaferin a ameliorates in vitro and in vivo pulmonary fibrosis by modulating the interplay of fibrotic, matricelluar proteins, and cytokines. Front Pharmacol 9:248","journal-title":"Front Pharmacol"},{"key":"527_CR4","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1016\/j.tiv.2014.04.011","volume":"28","author":"LN Bodduluru","year":"2014","unstructured":"Bodduluru LN, Kasala ER, Thota N, Barua CC, Sistla R (2014) Chemopreventive and therapeutic effects of nimbolide in cancer: the underlying mechanisms. Toxicol In Vitro 28:1026\u20131035","journal-title":"Toxicol In Vitro"},{"key":"527_CR5","doi-asserted-by":"publisher","first-page":"e0180751","DOI":"10.1371\/journal.pone.0180751","volume":"12","author":"L Cao","year":"2017","unstructured":"Cao L, Lafyatis R, Burkly LC (2017) Increased dermal collagen bundle alignment in systemic sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs. PLoS ONE 12:e0180751","journal-title":"PLoS ONE"},{"key":"527_CR6","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1158\/0008-5472.CAN-12-2233","volume":"73","author":"TR Cox","year":"2013","unstructured":"Cox TR, Bird D, Baker A-M, Barker HE, Ho MW, Lang G et al (2013) LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis. Cancer Res 73:1721\u20131732","journal-title":"Cancer Res"},{"key":"527_CR7","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.retram.2016.06.003","volume":"64","author":"N Do","year":"2016","unstructured":"Do N, Eming S (2016) Skin fibrosis: models and mechanisms. Curr Res Transl Med 64:185\u2013193","journal-title":"Curr Res Transl Med"},{"key":"527_CR8","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1186\/ar4230","volume":"15","author":"AJ Gilbane","year":"2013","unstructured":"Gilbane AJ, Denton CP, Holmes AM (2013) Scleroderma pathogenesis: a pivotal role for fibroblasts as effector cells. Arthritis Res Ther 15:215","journal-title":"Arthritis Res Ther"},{"key":"527_CR9","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S0009-8981(98)00060-6","volume":"274","author":"I Guevara","year":"1998","unstructured":"Guevara I, Iwanejko J, Dembi\u0144ska-Kie\u0107 A, Pankiewicz J, Wanat A, Anna P et al (1998) Determination of nitrite\/nitrate in human biological material by the simple Griess reaction. Clin Chim Acta 274:177\u2013188","journal-title":"Clin Chim Acta"},{"key":"527_CR10","doi-asserted-by":"publisher","first-page":"4465","DOI":"10.1158\/1078-0432.CCR-13-0080","volume":"19","author":"SC Gupta","year":"2013","unstructured":"Gupta SC, Prasad S, Sethumadhavan DR, Nair MS, Mo Y-Y, Aggarwal BB (2013) Nimbolide, a limonoid triterpene, inhibits growth of human colorectal cancer xenografts by suppressing the proinflammatory microenvironment. Clin Cancer Res 19:4465\u20134476","journal-title":"Clin Cancer Res"},{"key":"527_CR11","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1038\/jid.2008.431","volume":"129","author":"H Ishikawa","year":"2009","unstructured":"Ishikawa H, Takeda K, Okamoto A, S-i Matsuo, K-i Isobe (2009) Induction of autoimmunity in a bleomycin-induced murine model of experimental systemic sclerosis: an important role for CD4\u2009+\u2009T cells. J Investig Dermatol 129:1688\u20131695","journal-title":"J Investig Dermatol"},{"key":"527_CR12","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","journal-title":"J Dermatol"},{"key":"527_CR13","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1172\/JCI200320530","volume":"112","author":"R Kalluri","year":"2003","unstructured":"Kalluri R, Neilson EG (2003) Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Investig 112:1776\u20131784","journal-title":"J Clin Investig"},{"key":"527_CR14","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1016\/0006-291X(85)91315-4","volume":"131","author":"J Kelley","year":"1985","unstructured":"Kelley J, Chrin L, Shull S, Rowe DW, Cutroneo KR (1985) Bleomycin selectively elevates mRNA levels for procollagen and fibronectin following acute lung injury. Biochem Biophys Res Commun 131:836\u2013843","journal-title":"Biochem Biophys Res Commun"},{"key":"527_CR15","doi-asserted-by":"publisher","first-page":"iii14","DOI":"10.1093\/rheumatology\/kep108","volume":"48","author":"T Krieg","year":"2009","unstructured":"Krieg T, Takehara K (2009) Skin disease: a cardinal feature of systemic sclerosis. Rheumatology 48:iii14\u2013iii18","journal-title":"Rheumatology"},{"key":"527_CR16","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1186\/ar2188","volume":"9","author":"T Krieg","year":"2007","unstructured":"Krieg T, Abraham D, Lafyatis R (2007) Fibrosis in connective tissue disease: the role of the myofibroblast and fibroblast-epithelial cell interactions. Arthritis Res Ther 9:S4","journal-title":"Arthritis Res Ther"},{"key":"527_CR17","doi-asserted-by":"publisher","first-page":"S22","DOI":"10.1038\/ki.2010.418","volume":"78","author":"SB Lee","year":"2010","unstructured":"Lee SB, Kalluri R (2010) Mechanistic connection between inflammation and fibrosis. Kidney Int 78:S22\u2013S26","journal-title":"Kidney Int"},{"issue":"1","key":"527_CR18","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/jidsymp.2011.1","volume":"15","author":"M Meyer","year":"2011","unstructured":"Meyer M, M\u00fcller AK, Yang J, \u0160ulcov\u00e1 J, Werner S et al (2011) The role of chronic inflammation in cutaneous fibrosis: fibroblast growth factor receptor deficiency in keratinocytes as an example. J Investig Dermatol Symp Proc 15(1):48\u201352","journal-title":"J Investig Dermatol Symp Proc"},{"key":"527_CR19","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.redox.2016.12.011","volume":"11","author":"J Morry","year":"2017","unstructured":"Morry J, Ngamcherdtrakul W, Yantasee W (2017) Oxidative stress in cancer and fibrosis: opportunity for therapeutic intervention with anti-oxidant compounds, enzymes, and nanoparticles. Redox Biol 11:240\u2013253","journal-title":"Redox Biol"},{"key":"527_CR20","doi-asserted-by":"publisher","first-page":"283","DOI":"10.2217\/imt.13.173","volume":"6","author":"G Murdaca","year":"2014","unstructured":"Murdaca G, Span\u00f2 F, Contatore M, Guastalla A, Puppo F (2014) Potential use of TNF-\u03b1 inhibitors in systemic sclerosis. Immunotherapy 6:283\u2013289","journal-title":"Immunotherapy"},{"key":"527_CR21","doi-asserted-by":"publisher","first-page":"11929","DOI":"10.1073\/pnas.1507387112","volume":"112","author":"D Pilling","year":"2015","unstructured":"Pilling D, Vakil V, Cox N, Gomer RH (2015) TNF-\u03b1\u2013stimulated fibroblasts secrete lumican to promote fibrocyte differentiation. Proc Natl Acad Sci USA 112:11929\u201311934","journal-title":"Proc Natl Acad Sci USA"},{"key":"527_CR22","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1002\/art.38277","volume":"66","author":"D Rimar","year":"2014","unstructured":"Rimar D, Rosner I, Nov Y, Slobodin G, Rozenbaum M, Halasz K et al (2014) Brief report: lysyl oxidase is a potential biomarker of fibrosis in systemic sclerosis. Arthritis Rheumatol 66:726\u2013730","journal-title":"Arthritis Rheumatol"},{"key":"527_CR23","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/s40139-014-0062-y","volume":"2","author":"A Shroff","year":"2014","unstructured":"Shroff A, Mamalis A, Jagdeo J (2014) Oxidative stress and skin fibrosis. Curr Pathobiol Rep 2:257\u2013267","journal-title":"Curr Pathobiol Rep"},{"key":"527_CR24","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s00441-016-2464-0","volume":"365","author":"RC Stone","year":"2016","unstructured":"Stone RC, Pastar I, Ojeh N, Chen V, Liu S, Garzon KI et al (2016) Epithelial-mesenchymal transition in tissue repair and fibrosis. Cell Tissue Res 365:495\u2013506","journal-title":"Cell Tissue Res"},{"key":"527_CR25","doi-asserted-by":"publisher","first-page":"19819","DOI":"10.1038\/srep19819","volume":"6","author":"R Subramani","year":"2016","unstructured":"Subramani R, Gonzalez E, Arumugam A, Nandy S, Gonzalez V, Medel J et al (2016) Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition. Sci Rep 6:19819","journal-title":"Sci Rep"},{"key":"527_CR26","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1046\/j.1523-1747.2003.12308.x","volume":"121","author":"S Takagawa","year":"2003","unstructured":"Takagawa S, Lakos G, Mori Y, Varga J, Yamamoto T, Nishioka K (2003) Sustained activation of fibroblast transforming growth factor-\u03b2\/Smad signaling in a murine model of scleroderma. J Investig Dermatol 121:41\u201350","journal-title":"J Investig Dermatol"},{"key":"527_CR27","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3923\/jbs.2014.110.123","volume":"14","author":"R Tiwari","year":"2014","unstructured":"Tiwari R, Verma AK, Chakraborty S, Dhama K, Singh SV (2014) Neem (Azadirachta indica) and its potential for safeguarding health of animals and humans: a review. J Biol Sci 14:110\u2013123","journal-title":"J Biol Sci"},{"key":"527_CR28","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1002\/ijc.25788","volume":"129","author":"KA Trujillo","year":"2011","unstructured":"Trujillo KA, Heaphy CM, Mai M, Vargas KM, Jones AC, Vo P et al (2011) Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors. Int J Cancer 129:1310\u20131321","journal-title":"Int J Cancer"},{"key":"527_CR29","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.redox.2016.01.010","volume":"8","author":"F Ursini","year":"2016","unstructured":"Ursini F, Maiorino M, Forman HJ (2016) Redox homeostasis: the golden mean of healthy living. Redox Biol 8:205\u2013215","journal-title":"Redox Biol"},{"key":"527_CR30","doi-asserted-by":"publisher","first-page":"226","DOI":"10.2741\/s22","volume":"1","author":"J Varga","year":"2009","unstructured":"Varga J, Whitfield ML (2009) Transforming growth factor-beta in systemic sclerosis (scleroderma). Front Biosci (Sch Ed) 1:226\u2013235","journal-title":"Front Biosci (Sch Ed)"},{"issue":"7","key":"527_CR31","doi-asserted-by":"publisher","first-page":"3308","DOI":"10.1111\/jcmm.13630","volume":"22","author":"R Vona","year":"2018","unstructured":"Vona R, Giovannetti A, Gambardella L, Malorni W, Pietraforte D, Straface E (2018) Oxidative stress in the pathogenesis of systemic scleroderma: an overview. J Cell Mol Med 22(7):3308\u20133314","journal-title":"J Cell Mol Med"},{"key":"527_CR32","doi-asserted-by":"publisher","first-page":"805","DOI":"10.12968\/bjon.2006.15.15.21685","volume":"15","author":"H Wilson","year":"2006","unstructured":"Wilson H, Vincent R (2006) Autoimmune connective tissue disease: scleroderma. Br J Nurs 15:805\u2013809","journal-title":"Br J Nurs"},{"key":"527_CR33","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1111\/iwj.12034","volume":"11","author":"Y Wu","year":"2014","unstructured":"Wu Y, Huang S, Enhe J, Ma K, Yang S, Sun T et al (2014) Bone marrow-derived mesenchymal stem cell attenuates skin fibrosis development in mice. Int Wound J 11:701\u2013710","journal-title":"Int Wound J"},{"key":"527_CR34","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1002\/path.2277","volume":"214","author":"T Wynn","year":"2008","unstructured":"Wynn T (2008) Cellular and molecular mechanisms of fibrosis. J Pathol 214:199\u2013210","journal-title":"J Pathol"},{"key":"527_CR35","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/j.0906-6705.2005.00280.x","volume":"14","author":"T Yamamoto","year":"2005","unstructured":"Yamamoto T, Nishioka K (2005) Cellular and molecular mechanisms of bleomycin-induced murine scleroderma: current update and future perspective. Exp Dermatol 14:81\u201395","journal-title":"Exp Dermatol"},{"key":"527_CR36","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1046\/j.1523-1747.1999.00528.x","volume":"112","author":"T Yamamoto","year":"1999","unstructured":"Yamamoto T, Takagawa S, Katayama I, Yamazaki K, Hamazaki Y, Shinkai H et al (1999) Animal model of sclerotic skin. I: local injections of bleomycin induce sclerotic skin mimicking scleroderma. J Investig Dermatol 112:456\u2013462","journal-title":"J Investig Dermatol"},{"key":"527_CR37","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/ptr.5657","volume":"30","author":"J Yeon","year":"2016","unstructured":"Yeon J, Wook S, Pil J, Sung J (2016) Nimbolide inhibits nuclear factor\u00e2 \u00d0 B pathway in intestinal epithelial cells and macrophages and alleviates experimental colitis in mice. Phytother Res 30:1605\u20131614","journal-title":"Phytother Res"}],"container-title":["Inflammopharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-018-0527-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10787-018-0527-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-018-0527-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T02:49:43Z","timestamp":1751856583000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10787-018-0527-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,14]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["527"],"URL":"https:\/\/doi.org\/10.1007\/s10787-018-0527-4","relation":{},"ISSN":["0925-4692","1568-5608"],"issn-type":[{"value":"0925-4692","type":"print"},{"value":"1568-5608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,14]]},"assertion":[{"value":"19 July 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}