{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:34:35Z","timestamp":1792182875563,"version":"4.4.0"},"reference-count":63,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,3,27]],"date-time":"2012-03-27T00:00:00Z","timestamp":1332806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes is a prerequisite for remyelination after demyelination, and impairment of this process is suggested to be a major reason for remyelination failure. Diosgenin, a plant\u2010derived steroid, has been implicated for therapeutic use in many diseases, but little is known about its effect on the central nervous system. In this study, using a purified rat OPC culture model, we show that diosgenin significantly and specifically promotes OPC differentiation without affecting the viability, proliferation, or migration of OPC. Interestingly, the effect of diosgenin can be blocked by estrogen receptor (ER) antagonist ICI 182780 but not by glucocorticoid and progesterone receptor antagonist RU38486, nor by mineralocorticoid receptor antagonist spirolactone. Moreover, it is revealed that both ER\u2010alpha and ER\u2010beta are expressed in OPC, and diosgenin can activate the extracellular signal\u2010regulated kinase 1\/2 (ERK1\/2) in OPC via ER. The pro\u2010differentiation effect of diosgenin can also be obstructed by the ERK inhibitor PD98059. Furthermore, in the cuprizone\u2010induced demyelination model, it is demonstrated that diosgenin administration significantly accelerates\/enhances remyelination as detected by Luxol fast blue stain, MBP immunohistochemistry and real time RT\u2010PCR. Diosgenin also increases the number of mature oligodendrocytes in the corpus callosum while it does not affect the number of OPCs. Taking together, our results suggest that diosgenin promotes the differentiation of OPC into mature oligodendrocyte through an ER\u2010mediated ERK1\/2 activation pathway to accelerate remyelination, which implicates a novel therapeutic usage of this steroidal natural product in demyelinating diseases such as multiple sclerosis (MS). \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/glia.22333","type":"journal-article","created":{"date-parts":[[2012,3,29]],"date-time":"2012-03-29T07:49:14Z","timestamp":1333007354000},"page":"1037-1052","source":"Crossref","is-referenced-by-count":71,"title":["Diosgenin promotes oligodendrocyte progenitor cell differentiation through estrogen receptor\u2010mediated ERK1\/2 activation to accelerate remyelination"],"prefix":"10.1002","volume":"60","author":[{"given":"Lin","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dazhi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiran","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,3,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20806"},{"key":"e_1_2_5_3_1","first-page":"335","article-title":"The effects of sustained delivery of diosgenin on the adrenal gland of female rats","volume":"39","author":"Benghuzzi H","year":"2003","journal-title":"Biomed Sci Instrum"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2009.06.004"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(02)00191-0"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80155-5"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010994"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020164"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.24.3243"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg081"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-7431(03)00210-0"},{"key":"e_1_2_5_12_1","first-page":"38","article-title":"The interaction of MS, pregnancy: A critical review","volume":"10","author":"Dwosh E","year":"2003","journal-title":"Int MS J"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn917"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2480"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3239-10.2011"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80359-1"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(92)90179-C"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.21061"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22486"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-06-02218.2000"},{"key":"e_1_2_5_21_1","first-page":"3833","article-title":"Estrogenic effects of genistein on the growth of estrogen receptor\u2010positive human breast cancer (MCF\u20107) cells in vitro and in vivo","volume":"58","author":"Hsieh CY","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.10.050"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn080"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.wco.0000169735.60922.fb"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2009.04.004"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5485.1754"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn096"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01691-X"},{"key":"e_1_2_5_29_1","first-page":"458","article-title":"Evidence for pathogenic heterogeneity in multiple sclerosis","volume":"55","author":"Lucchinetti CF","year":"2004","journal-title":"Ann Neurol"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920206779315737"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2001.tb00385.x"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.85.3.890"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1995"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025783412651"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl217"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(00)00194-7"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.018234"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635580802357352"},{"key":"e_1_2_5_39_1","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1158\/1055-9965.1392.13.8","article-title":"Diosgenin A steroid saponin of Trigonella foenum\u2010graecum (Fenugreek), inhibits azoxymethane\u2010induced aberrant crypt foci formation in F344 rats and induces apoptosis in HT\u201029 human colon cancer cells","volume":"13","author":"Raju J","year":"2004","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-1573(199905)13:3<197::AID-PTR413>3.0.CO;2-L"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.6.11.1657"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.3.321"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02543970"},{"key":"e_1_2_5_44_1","first-page":"13","article-title":"The prevention of osteoporotic progression by means of steroid loaded TCPL drug delivery systems","volume":"37","author":"Scott A","year":"2001","journal-title":"Biomed Sci Instrum"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10301"},{"key":"e_1_2_5_46_1","volume-title":"Atlas of the mouse brain and spinal cord","author":"Sidman RL","year":"1971"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.6267"},{"key":"e_1_2_5_48_1","doi-asserted-by":"crossref","first-page":"8331","DOI":"10.1523\/JNEUROSCI.18-20-08331.1998","article-title":"Multiple restricted origin of oligodendrocytes","volume":"15","author":"Spassky N","year":"1998","journal-title":"J Neurosci"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4547(20010215)63:4<303::AID-JNR1024>3.0.CO;2-A"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24419"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2010.1597"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2009.01.006"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.03.016"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0234-09.2009"},{"key":"e_1_2_5_55_1","first-page":"60","article-title":"Hormone\u2010based therapies in MS","volume":"10","author":"Voskuhl RR","year":"2003","journal-title":"Int MS J"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021792"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0029-7844(02)02502-4"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-02-00601.1998"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2009-0422"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.188854"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-1652"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-011-1838-2"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.010082"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02388.x"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.22333","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.22333","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T07:29:10Z","timestamp":1700551750000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.22333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,27]]},"references-count":63,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2012,7]]}},"alternative-id":["10.1002\/glia.22333"],"URL":"https:\/\/doi.org\/10.1002\/glia.22333","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3,27]]}}}