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However, current knowledge of its mechanisms is incomplete. In this study, integrated spleen and thymus untargeted metabolomics were used to analyze the changes in endogenous metabolites underlying the immunosuppressive activity of TWD on psoriasis animal models induced by imiquimod. The results suggested that TWD treatment markedly attenuated imiquimod\u2010induced psoriasis and showed significant immunosuppressive activity as evidenced by decreased elevation index of spleen and thymus. Meanwhile, TWD significantly reversed the elevation of immunoregulatory factors, including IL\u201010, IL\u201017, IL\u201022 and IL\u201023. Multivariate trajectory analysis revealed that TWD treatment could restore the psoriasis\u2010disturbed spleen and thymus metabolite profiles towards the normal metabolic status. A total of 25 and 27 metabolites associated with the immunomodulatory effects for which levels changed markedly upon treatment have been identified in spleen and thymus, respectively. These differential metabolites were mainly involved in amino acid metabolism, nucleotide metabolism, fatty acid metabolism and lipid metabolism. Our investigation provided a holistic view of TWD for intervention in psoriasis through immunoregulation and provided further scientific information <jats:italic>in vivo<\/jats:italic> about a clinical value of TWD for psoriasis.<\/jats:p>","DOI":"10.1002\/bmc.4881","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T14:39:19Z","timestamp":1589294359000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Spleen and thymus metabolomics strategy to explore the immunoregulatory mechanism of total withanolides from the leaves of <scp><i>Datura metel<\/i><\/scp> L. on imiquimod\u2010induced psoriatic skin dermatitis in mice"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3705-0717","authenticated-orcid":false,"given":"Yangang","family":"Cheng","sequence":"first","affiliation":[{"name":"Key Laboratory of Chinese Materia Medica Ministry of Education of Heilongjiang University of Chinese Medicine  Harbin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Materia Medica Ministry of Education of Heilongjiang University of Chinese Medicine  Harbin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyan","family":"Tan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Materia Medica Ministry of Education of Heilongjiang University of Chinese Medicine  Harbin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanping","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Materia Medica Ministry of Education of Heilongjiang University of Chinese Medicine  Harbin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Guan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Materia Medica Ministry of Education of Heilongjiang University of Chinese Medicine  Harbin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Materia Medica Ministry of Education of Heilongjiang University of Chinese Medicine  Harbin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingyou","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Materia Medica Ministry of Education of Heilongjiang University of Chinese Medicine  Harbin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haixue","family":"Kuang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Materia Medica Ministry of Education of Heilongjiang University of Chinese Medicine  Harbin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01549"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02789"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo9100227"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-017-2282-6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19010179"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1448-3"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-010-0215-x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2016.04.016"},{"issue":"4","key":"e_1_2_8_10_1","first-page":"305","article-title":"Osteopontin deficiency affects imiquimod\u2010induced psoriasis\u2010like murine skin\u2010inflammation and lymphocyte distribution in skin, draining lymph nodes and spleen Exp","volume":"24","author":"Frenzel D. 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