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However, 20% prolactinomas patients did not respond to bromocriptine. Hordenine is an alkaloid separated from Fructus Hordei Germinatus, which showed significant antihyperprolactinemia activity in rats. The aim of this study was to explore the effect and mechanism of hordenine on prolactinomas in rats. The study used estradiol to induce prolactinomas, which caused the activation of the pituitary mitogen\u2010activated protein kinase (MAPK) pathway in rats significantly. The treatment of hordenine restored estradiol, induced the overgrowth of pituitary gland, and reduced the prolactin (PRL) accumulation in the serum and pituitary gland of rats by blocking the MAPK (p38, ERK1\/2, and JNK) activation and production of inflammatory cytokines, tumor necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic> (TNF\u2010<jats:italic>\u03b1<\/jats:italic>), interleukin\u20101<jats:italic>\u03b2<\/jats:italic> (IL\u20101<jats:italic>\u03b2<\/jats:italic>), and interleukin\u20106 (IL\u20106). The antiprolactinoma effect of hordenine was mediated by inhibiting the MAPK signaling pathway activation in rats.<\/jats:p>","DOI":"10.1155\/2020\/3107290","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T23:34:09Z","timestamp":1587684849000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Antiprolactinoma Effect of Hordenine by Inhibiting MAPK Signaling Pathway Activation in Rats"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4888-7638","authenticated-orcid":false,"given":"Xiong","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Run-zhu","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiao-yan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-hua","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6109-8767","authenticated-orcid":false,"given":"Yong-gang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7630-9528","authenticated-orcid":false,"given":"Jin-hu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,23]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1677\/erc.1.01131"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2014.11.004"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2009.05.008"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2009.03667.x"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20412"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-005-5079-0"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2015.03.058"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.22.6.0451"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2015.03.059"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje-12-0236"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28864"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.9.9.7601337"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.12.012"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-13-1007"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.26.5.4689"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206478"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.476"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811x-2-5"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo_00000285"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-09-2918"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m204863200"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-004-3503-x"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11425"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1137463100"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.m400008-mcp200"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m001281200"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-08-4455"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m703857200"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgr079"},{"key":"e_1_2_11_30_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/579054"},{"key":"e_1_2_11_31_2","first-page":"2087","article-title":"Therapeutic effects of total alkaloids of Fructus Hordei Germinatus in hyperprolactinemis rats","volume":"27","author":"Xiong W.","year":"2014","journal-title":"Pakistan Journal of Pharmaceutical Sciences"},{"key":"e_1_2_11_32_2","first-page":"2386","article-title":"Inhibition effects of hordenine on prolactin secretion in hyperprolactinemia rats","volume":"40","author":"Guo R. 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