Int J Biol Sci 2024; 20(6):2236-2260. doi:10.7150/ijbs.90483 This issue Cite
Research Paper
1. Sichuan Key Medical Laboratory of New Drug Discovery and Druggability, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou,646000, China.
2. School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China.
3. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
4. Education Ministry Key Laboratory of Medical Electrophysiology, Southwest Medical University, Luzhou 646000, China.
† These authors contributed equally to this work and shared the first authorship.
Thrombocytopenia, a prevalent hematologic challenge, correlates directly with the mortality of numerous ailments. Current therapeutic avenues for thrombocytopenia are not without limitations. Here, we identify genistin, an estrogen analogue, as a promising candidate for thrombocytopenia intervention, discovered through AI-driven compound library screening. While estrogen's involvement in diverse biological processes is recognized, its role in thrombopoiesis remains underexplored. Our findings elucidate genistin's ability to enhance megakaryocyte differentiation, thereby augmenting platelet formation and production. In vivo assessments further underscore genistin's remedial potential against radiation-induced thrombocytopenia. Mechanistically, genistin's efficacy is attributed to its direct interaction with estrogen receptor β (ERβ), with subsequent activation of both ERK1/2 and the Akt signaling pathways membrane ERβ. Collectively, our study positions genistin as a prospective therapeutic strategy for thrombocytopenia, shedding light on novel interplays between platelet production and ERβ.
Keywords: Estrogen Analogue, Genistin, ERβ, thrombocytopenia