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In cyclophosphamide-induced immunosuppressed mice, PD was evaluated for its immunomodulatory effects. Immune organ indices were measured, while H&amp;E staining and ELISA assessed spleen pathology and serum cytokine levels. The proliferation of splenic lymphocytes, both total and subpopulation, was determined using concanavalin A or lipopolysaccharide stimulation, with flow cytometry analyzing peripheral blood and splenic lymphocytes, thymic T cell subtypes, cell cycling, and bromodeoxyuridine incorporation. Western blotting was used to assess Ki67, PCNA expression, and MAPK activation. PD significantly alleviated cyclophosphamide-induced reductions in spleen and thymus indices, improved the organization of red and white pulp in the spleen, and restored TNF-\u03b1 and IFN-\u03b3 levels. It reversed cyclophosphamide-induced cell cycle arrest, characterized by increased PCNA and decreased Ki67, and corrected the diminished numbers of B and T cells and the reduced CD4+\/CD8+ ratio in the thymus. In vitro, PD directly promoted splenic lymphocyte proliferation and cell cycling via MAPK activation. Overall, our findings demonstrated that PD alleviated mouse immunosuppression by activating splenic lymphocyte proliferation and re-organizing thymic T cell development and differentiation.<\/jats:p>","DOI":"10.3390\/ijms26062800","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T05:03:59Z","timestamp":1742447039000},"page":"2800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Polydatin Alleviates Cyclophosphamide-Induced Mouse Immunosuppression by Promoting Splenic Lymphocyte Proliferation and Thymic T Cell Development and Differentiation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8107-3732","authenticated-orcid":false,"given":"Na","family":"Sun","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuping","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingdi","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease, Immunology Department, Ministry of Education, Tianjin Medical University, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Miao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/nrc749","article-title":"DNA and its associated processes as targets for cancer therapy","volume":"2","author":"Hurley","year":"2002","journal-title":"Nat. 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