{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:02:24Z","timestamp":1789549344229,"version":"build-2803163510"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"name":"Zhejiang Province Natural Science Foundation","award":["LQ18H080003"],"award-info":[{"award-number":["LQ18H080003"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903959"],"award-info":[{"award-number":["81903959"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Biol Rep"],"published-print":{"date-parts":[[2022,9]]},"DOI":"10.1007\/s11033-022-07645-1","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T08:02:52Z","timestamp":1655366572000},"page":"8317-8324","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Icariin protects bone marrow mesenchymal stem cells in aplastic anemia by targeting MAPK pathway"],"prefix":"10.1007","volume":"49","author":[{"given":"Shu","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7816-6065","authenticated-orcid":false,"given":"Jianping","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"7645_CR1","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1080\/16078454.2019.1642548","volume":"24","author":"L Wang","year":"2019","unstructured":"Wang L, Liu H (2019) Pathogenesis of aplastic anemia. Hematology 24:559\u2013566","journal-title":"Hematology"},{"key":"7645_CR2","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1182\/asheducation-2013.1.76","volume":"2013","author":"NS Young","year":"2013","unstructured":"Young NS (2013) Current concepts in the pathophysiology and treatment of aplastic anemia. Hematol Am Soc Hematol Educ Prog 2013:76\u201381","journal-title":"Hematol Am Soc Hematol Educ Prog"},{"key":"7645_CR3","doi-asserted-by":"publisher","first-page":"52","DOI":"10.2991\/chi.d.190321.002","volume":"1","author":"EE Solomou","year":"2019","unstructured":"Solomou EE (2019) Idiopathic aplastic anemia: an update. Clin Hematol Int 1:52\u201357","journal-title":"Clin Hematol Int"},{"key":"7645_CR4","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1111\/bjh.14110","volume":"174","author":"H Zhu","year":"2016","unstructured":"Zhu H, Luo RM, Luan Z, Lee V, Zhu YP, Luo CJ et al (2016) Unmanipulated haploidentical haematopoietic stem cell transplantation for children with severe aplastic anaemia. Br J Haematol 174:799\u2013805","journal-title":"Br J Haematol"},{"key":"7645_CR5","doi-asserted-by":"publisher","first-page":"e5905","DOI":"10.1097\/MD.0000000000005905","volume":"96","author":"R Fu","year":"2017","unstructured":"Fu R, Chen T, Song J, Wang G, Li L, Ruan E et al (2017) De-escalation empirical antibiotic therapy improved survival for patients with severe aplastic anemia treated with antithymocyte globulin. Medicine 96:e5905","journal-title":"Medicine"},{"key":"7645_CR6","doi-asserted-by":"publisher","first-page":"e382","DOI":"10.3324\/haematol.2017.171215","volume":"102","author":"JGK van der Hem","year":"2017","unstructured":"van der Hem JGK, de Wreede LC, Brand A, Veelken H, Falkenburg JHF, Halkes CJM (2017) Long-term risk of cancer development in adult patients with idiopathic aplastic anemia after treatment with anti-thymocyte globulin. Haematologica 102:e382\u2013e383","journal-title":"Haematologica"},{"key":"7645_CR7","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/j.1752-8062.2008.00074.x","volume":"2","author":"IN Shipounova","year":"2009","unstructured":"Shipounova IN, Petrova TV, Svinareva DA, Momotuk KS, Mikhailova EA, Drize NI (2009) Alterations in hematopoietic microenvironment in patients with aplastic anemia. Clin Transl Sci 2:67\u201374","journal-title":"Clin Transl Sci"},{"key":"7645_CR8","doi-asserted-by":"publisher","first-page":"107292","DOI":"10.1016\/j.intimp.2020.107292","volume":"93","author":"H Li","year":"2021","unstructured":"Li H, Xu X, Wang D, Zhang Y, Chen J, Li B et al (2021) Hypermethylation-mediated downregulation of long non-coding rna meg3 inhibits osteogenic differentiation of bone marrow mesenchymal stem cells and promotes pediatric aplastic anemia. Int Immunopharmacol 93:107292","journal-title":"Int Immunopharmacol"},{"key":"7645_CR9","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1093\/jmcb\/mjp030","volume":"2","author":"R Sugimura","year":"2010","unstructured":"Sugimura R, Li L (2010) Shifting in balance between osteogenesis and adipogenesis substantially influences hematopoiesis. J Mol Cell Biol 2:61\u201362","journal-title":"J Mol Cell Biol"},{"key":"7645_CR10","doi-asserted-by":"publisher","first-page":"276862","DOI":"10.1155\/2014\/276862","volume":"2014","author":"NK Tripathy","year":"2014","unstructured":"Tripathy NK, Singh SP, Nityanand S (2014) Enhanced adipogenicity of bone marrow mesenchymal stem cells in aplastic anemia. Stem Cells Int 2014:276862","journal-title":"Stem Cells Int"},{"key":"7645_CR11","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1017\/S0007114518000399","volume":"119","author":"S Luo","year":"2018","unstructured":"Luo S, Chen Y, Zhao L, Qi X, Miao X, Zhou H et al (2018) Effect of nutritional supplement on bone marrow-derived mesenchymal stem cells from aplastic anaemia. Br J Nutr 119:748\u2013758","journal-title":"Br J Nutr"},{"key":"7645_CR12","doi-asserted-by":"publisher","first-page":"2460","DOI":"10.1080\/15384101.2020.1807081","volume":"19","author":"H Li","year":"2020","unstructured":"Li H, Xu X, Wang D, Zeng L, Li B, Zhang Y et al (2020) Mir-146b-5p regulates bone marrow mesenchymal stem cell differentiation by siah2\/ppar\u03b3 in aplastic anemia children and benzene-induced aplastic anemia mouse model. Cell Cycle 19:2460\u20132471","journal-title":"Cell Cycle"},{"key":"7645_CR13","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.3736\/jcim20111104","volume":"9","author":"Y Chen","year":"2011","unstructured":"Chen Y, Huang JH, Ning Y, Shen ZY (2011) [icariin and its pharmaceutical efficacy: research progress of molecular mechanism]. Zhong Xi Yi Jie He Xue Bao 9:1179\u20131184","journal-title":"Zhong Xi Yi Jie He Xue Bao"},{"key":"7645_CR14","first-page":"1245","volume":"59","author":"X Zhang","year":"2021","unstructured":"Zhang X, Chen Y, Zhang C, Zhang X, Xia T, Han J et al (2021) Effects of icariin on the fracture healing in young and old rats and its mechanism. Pharm Biol 59:1245\u20131255","journal-title":"Pharm Biol"},{"key":"7645_CR15","doi-asserted-by":"crossref","first-page":"8085325","DOI":"10.1155\/2017\/8085325","volume":"2017","author":"JM Huang","year":"2017","unstructured":"Huang JM, Bao Y, Xiang W, Jing XZ, Guo JC, Yao XD et al (2017) Icariin regulates the bidirectional differentiation of bone marrow mesenchymal stem cells through canonical wnt signaling pathway. Evid Based Complement Alternat Med 2017:8085325","journal-title":"Evid Based Complement Alternat Med"},{"key":"7645_CR16","first-page":"7125","volume":"8","author":"S Qin","year":"2015","unstructured":"Qin S, Zhou W, Liu S, Chen P, Wu H (2015) Icariin stimulates the proliferation of rat bone mesenchymal stem cells via erk and p38 mapk signaling. Int J Clin Exp Med 8:7125\u20137133","journal-title":"Int J Clin Exp Med"},{"key":"7645_CR17","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.biochi.2004.10.018","volume":"87","author":"F Bost","year":"2005","unstructured":"Bost F, Aouadi M, Caron L, Bin\u00e9truy B (2005) The role of mapks in adipocyte differentiation and obesity. Biochimie 87:51\u201356","journal-title":"Biochimie"},{"key":"7645_CR18","doi-asserted-by":"crossref","unstructured":"Cho JH, Lee JH, Lee KM, Lee CK, Shin DM (2021) Bmp-2 induced signaling pathways and phenotypes: comparisons between senescent and non-senescent bone marrow mesenchymal stem cells. Calcif Tissue Int","DOI":"10.1007\/s00223-021-00923-3"},{"key":"7645_CR19","doi-asserted-by":"publisher","first-page":"e0172954","DOI":"10.1371\/journal.pone.0172954","volume":"12","author":"Q Zhao","year":"2017","unstructured":"Zhao Q, Lu Y, Gan X, Yu H (2017) Low magnitude high frequency vibration promotes adipogenic differentiation of bone marrow stem cells via p38 mapk signal. PLoS ONE 12:e0172954","journal-title":"PLoS ONE"},{"key":"7645_CR20","first-page":"14","volume":"54","author":"X Xu","year":"2016","unstructured":"Xu X, Li X, Yan R, Jiang H, Wang T, Fan L et al (2016) Gene expression profiling of human bone marrow-derived mesenchymal stem cells during adipogenesis. Folia Histochem Cytobiol 54:14\u201324","journal-title":"Folia Histochem Cytobiol"},{"key":"7645_CR21","doi-asserted-by":"publisher","first-page":"6815620","DOI":"10.1155\/2019\/6815620","volume":"2019","author":"Q Shang","year":"2019","unstructured":"Shang Q, Yu X, Ren H, Shen G, Zhao W, Zhang Z et al (2019) Effect of plastrum testudinis extracts on the proliferation and osteogenic differentiation of rbmscs by regulating p38 mapk-related genes. Evid Based Complement Alternat Med 2019:6815620","journal-title":"Evid Based Complement Alternat Med"},{"key":"7645_CR22","doi-asserted-by":"publisher","first-page":"3004","DOI":"10.3390\/ijms19103004","volume":"19","author":"K Lee","year":"2018","unstructured":"Lee K, Seo I, Choi MH, Jeong D (2018) Roles of mitogen-activated protein kinases in osteoclast biology. Int J Mol Sci 19:3004","journal-title":"Int J Mol Sci"},{"key":"7645_CR23","doi-asserted-by":"publisher","first-page":"663959","DOI":"10.3389\/fcell.2021.663959","volume":"9","author":"F Xiao","year":"2021","unstructured":"Xiao F, Tang CY, Tang HN, Wu HX, Hu N, Li L et al (2021) Long non-coding rna 332443 inhibits preadipocyte differentiation by targeting runx1 and p38-mapk and erk1\/2-mapk signaling pathways. Front Cell Dev Biol 9:663959","journal-title":"Front Cell Dev Biol"},{"key":"7645_CR24","doi-asserted-by":"publisher","first-page":"730776","DOI":"10.3389\/fphar.2021.730776","volume":"12","author":"ML Chiu","year":"2021","unstructured":"Chiu ML, Hsu YL, Chen CJ, Li TM, Chiou JS, Tsai FJ et al (2021) Chinese herbal medicine therapy reduces the risks of overall and anemia-related mortalities in patients with aplastic anemia: a nationwide retrospective study in taiwan. Front Pharmacol 12:730776","journal-title":"Front Pharmacol"},{"issue":"2","key":"7645_CR25","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1002\/jcb.27516","volume":"120","author":"S Deng","year":"2019","unstructured":"Deng S, Zeng Y, Wu L, Hu Z, Shen J, Shen Y et al (2019) The regulatory roles of vegf-notch signaling pathway on aplastic anemia with kidney deficiency and blood stasis. J Cell Biochem 120(2):2078\u20132089","journal-title":"J Cell Biochem"},{"key":"7645_CR26","doi-asserted-by":"publisher","first-page":"153485","DOI":"10.1016\/j.phymed.2021.153485","volume":"85","author":"Y Xu","year":"2021","unstructured":"Xu Y, Jiang Y, Jia B, Wang Y, Li T (2021) Icariin stimulates osteogenesis and suppresses adipogenesis of human bone mesenchymal stem cells via mir-23a-mediated activation of the wnt\/\u03b2-catenin signaling pathway. Phytomedicine 85:153485","journal-title":"Phytomedicine"},{"key":"7645_CR27","doi-asserted-by":"publisher","first-page":"4496","DOI":"10.1111\/jcmm.13761","volume":"22","author":"L-L Liu","year":"2018","unstructured":"Liu L-L, Liu L, Liu H-H, Ren S-S, Dou C-Y, Cheng P-P et al (2018) Levamisole suppresses adipogenesis of aplastic anaemia-derived bone marrow mesenchymal stem cells through zfp36l1-ppargc1b axis. J Cell Mol Med 22:4496\u20134506","journal-title":"J Cell Mol Med"},{"key":"7645_CR28","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s00277-009-0892-6","volume":"89","author":"YH Chao","year":"2010","unstructured":"Chao YH, Peng CT, Harn HJ, Chan CK, Wu KH (2010) Poor potential of proliferation and differentiation in bone marrow mesenchymal stem cells derived from children with severe aplastic anemia. Ann Hematol 89:715\u2013723","journal-title":"Ann Hematol"},{"key":"7645_CR29","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1007\/s00198-017-4255-1","volume":"29","author":"Z Wang","year":"2018","unstructured":"Wang Z, Wang D, Yang D, Zhen W, Zhang J, Peng S (2018) The effect of icariin on bone metabolism and its potential clinical application. Osteoporos Int 29:535\u2013544","journal-title":"Osteoporos Int"},{"key":"7645_CR30","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1111\/cpr.12185","volume":"48","author":"Y Wu","year":"2015","unstructured":"Wu Y, Xia L, Zhou Y, Xu Y, Jiang X (2015) Icariin induces osteogenic differentiation of bone mesenchymal stem cells in a mapk-dependent manner. Cell Prolif 48:375\u2013384","journal-title":"Cell Prolif"},{"key":"7645_CR31","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.3892\/etm.2017.4128","volume":"13","author":"H Liu","year":"2017","unstructured":"Liu H, Xiong Y, Zhu X, Gao H, Yin S, Wang J et al (2017) Icariin improves osteoporosis, inhibits the expression of ppar\u03b3, c\/ebp\u03b1, fabp4 mrna, n1icd and jagged1 proteins, and increases notch2 mrna in ovariectomized rats. Exp Ther Med 13:1360\u20131368","journal-title":"Exp Ther Med"},{"key":"7645_CR32","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1002\/jcp.25102","volume":"231","author":"C Ge","year":"2016","unstructured":"Ge C, Cawthorn WP, Li Y, Zhao G, Macdougald OA, Franceschi RT (2016) Reciprocal control of osteogenic and adipogenic differentiation by erk\/map kinase phosphorylation of runx2 and ppar\u03b3 transcription factors. J Cell Physiol 231:587\u2013596","journal-title":"J Cell Physiol"},{"key":"7645_CR33","unstructured":"Gao Q, Jiang Y, Dai S, Wang B, Gao F, Guo C, et al (2012) Interleukin 17a exacerbates atherosclerosis by promoting fatty acid-binding protein 4-mediated er stress in macrophages. Circ Res"},{"key":"7645_CR34","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.3390\/ijms21072346","volume":"21","author":"J Yue","year":"2020","unstructured":"Yue J, L\u00f3pez JM (2020) Understanding mapk signaling pathways in apoptosis. Int J Mol Sci 21:2346","journal-title":"Int J Mol Sci"},{"key":"7645_CR35","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s40001-021-00559-x","volume":"26","author":"Z Li","year":"2021","unstructured":"Li Z, Wang X, Hong TP, Wang HJ, Gao ZY, Wan M (2021) Advanced glycosylation end products inhibit the proliferation of bone-marrow stromal cells through activating mapk pathway. Eur J Med Res 26:94","journal-title":"Eur J Med Res"}],"container-title":["Molecular Biology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-022-07645-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11033-022-07645-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-022-07645-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T01:16:05Z","timestamp":1727399765000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11033-022-07645-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,16]]},"references-count":35,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["7645"],"URL":"https:\/\/doi.org\/10.1007\/s11033-022-07645-1","relation":{},"ISSN":["0301-4851","1573-4978"],"issn-type":[{"value":"0301-4851","type":"print"},{"value":"1573-4978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,16]]},"assertion":[{"value":"24 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2022","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 have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of The First Affiliated Hospital of Zhejiang Chinese Medical University.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}