{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T19:03:06Z","timestamp":1779822186321,"version":"3.53.1"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Psoriasis is an immune\u2010mediated chronic inflammatory skin disease. Radix Rehmanniae Praeparata (RRP) is a traditional Chinese medicine with abundant biological functions. This study was performed to analyze the potential functional mechanism of RRP using network pharmacology, machine learning, molecular docking, and cell experiments. Active ingredients of RRP were screened from the TCMSP database, and targets were obtained from TCMSP and Swiss Target Prediction. Targets of psoriasis were acquired from GSE274560, GeneCards, and CTD. The protein\u2013protein interaction network was analyzed by the String website. KEGG, Reactome, and GO were analyzed to predict possible pathways. LASSO and SVM\u2010RFE machine learning algorithms were used to screen significant targets. Interaction between active ingredients and core targets was validated by molecular docking and molecular dynamics simulation. In\u00a0vitro cell experiments were conducted using human keratinocytes HaCaT, including CCK\u20108, Western blotting, EdU, and ELISA. Sitosterol and Stigmasterol acted as the active ingredients of RRP. A total of 145 targets for the two ingredients were screened, and 18,871 targets were obtained for psoriasis. Furthermore, 27 intersection targets were considered as the candidate target genes of RRP for psoriasis treatment. LASSO and SVM\u2010RFE identified RORC and HSD11B1 as core targets. Molecular docking showed the binding between Sitosterol or Stigmasterol and RORC or HSD11B1. Molecular dynamics simulation further validated the binding between Stigmasterol and RORC or HSD11B1. Cell experiments indicated that Stigmasterol inhibited HaCaT proliferation and inflammation via inducing HSD11B1 upregulation. These findings demonstrate that the mechanism of RRP in psoriasis is multi\u2010target and multi\u2010pathway. This study has unraveled the preliminary mechanism of RRP in treating psoriasis, which involves Stigmasterol\u2010mediated HSD11B1 upregulation.<\/jats:p>","DOI":"10.1111\/cbdd.70309","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:31:36Z","timestamp":1778650296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network Pharmacology, Machine Learning, Molecular Docking, and Cell Experiments Reveal the Therapeutic Mechanism of Radix Rehmanniae Praeparata in Psoriasis In\u00a0Vitro"],"prefix":"10.1111","volume":"107","author":[{"given":"Tingting","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine Wujin People's Hospital  Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Acupuncture Wujin People's Hospital  Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine Wujin People's Hospital  Changzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5172-8391","authenticated-orcid":false,"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Dermatology Wujin People's Hospital  Changzhou 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