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Thrombocytopenia, a common and challenging hematological disorder, often coexists with serious illnesses. Previous research has shown a correlation between HM and thrombocytopenia, but the mechanism needs further elucidation. The aim of this study was to clarify the mechanisms underlying the effects of HM on thrombocytopenia and to develop new therapeutic strategies. Flow cytometry, Giemsa staining, and Phalloidin staining were used to assess HM's impact on Meg\u201001 and HEL cell differentiation and maturation in vitro. A radiation\u2010induced thrombocytopenic mouse model was employed to evaluate HM's effect on platelet production in vivo. Network pharmacology, molecular docking, and protein blotting were utilized to investigate HM's targets and mechanisms. The results demonstrated that HM dose\u2010dependently promoted Meg\u201001 and HEL cell differentiation and maturation in vitro and restored platelet levels in irradiated mice in vivo. Subsequently, HM was found to be involved in the biological process of platelet production by upregulating the expressions of Rac1, Cdc42, JNK, and 5\u2010HTR2A. Furthermore, the targeting of HM to 5\u2010HTR2A and its correlation with downstream Rac1\/Cdc42\/JNK were also confirmed. In conclusion, HM regulates megakaryocyte differentiation and thrombopoiesis through the 5\u2010HTR2A and Rac1\/Cdc42\/JNK pathways, providing a potential treatment strategy for thrombocytopenia.<\/jats:p>","DOI":"10.1002\/ptr.8317","type":"journal-article","created":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T08:34:39Z","timestamp":1723883679000},"page":"5134-5149","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Harmine promotes megakaryocyte differentiation and thrombopoiesis by activating the Rac1\/Cdc42\/<scp>JNK<\/scp> pathway through a potential target of 5\u2010<scp>HTR2A<\/scp>"],"prefix":"10.1002","volume":"38","author":[{"given":"Xiaoxi","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmacy Southwest Medical University  Luzhou China"},{"name":"School of Basic Medical Sciences Southwest Medical University  Luzhou 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