National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Mediators Inflamm. 2018 Aug 27;2018:7235639. doi: 10.1155/2018/7235639. eCollection 2018.
Immune thrombocytopenia (ITP) is a common acquired autoimmune disease, and thrombopoietin (TPO) is an important cytokine that regulates the production of megakaryocytes and platelets. We have identified a biologically active component, icaritin, from a Chinese herba epimedii extract. Icaritin promotes platelet production and regulates T cell polarization, but its mechanism is not clear. In this study, the BALB/c mouse model of ITP was established by injection of an antiplatelet antibody every other day for seven total times. The antiplatelet sera were derived from guinea pigs immunized with the platelets of BALB/c mice. Mice with ITP were treated with icaritin at low, moderate, or high doses of 4.73, 9.45, and 18.90 mg/kg, respectively, for fourteen consecutive days. The present study shows that icaritin can significantly increase peripheral blood platelet counts and thrombocytocrit, increase the TPO level in serum, attenuate splenomegaly, and reduce the abnormal proliferation of megakaryocytes in the spleen and bone marrow. Icaritin can also downregulate the expression of bone marrow TPO, myeloproliferative leukemia virus oncogene (MPL), and p-Stat3. Our results suggest that icaritin can significantly improve the health of mice with ITP via possible downregulation of p-Stat3 expression in the JAK2/Stat3 phosphorylation signaling pathway and regulation of bone marrow TPO/MPL metabolism.
免疫性血小板减少症（ITP）是一种常见的获得性自身免疫性疾病，而血小板生成素（TPO）是调节巨核细胞和血小板生成的重要细胞因子。我们从一种中药淫羊藿提取物中鉴定出一种具有生物活性的成分，即淫羊藿次苷。淫羊藿次苷能促进血小板生成并调节 T 细胞极化，但具体机制尚不清楚。在这项研究中，通过每隔一天注射抗血小板抗体总共 7 次，建立了 BALB/c 小鼠 ITP 模型。抗血小板血清来自用 BALB/c 小鼠血小板免疫的豚鼠。ITP 小鼠用低、中、高剂量（4.73、9.45 和 18.90mg/kg）的淫羊藿次苷连续治疗 14 天。本研究表明，淫羊藿次苷能显著增加外周血血小板计数和血小板压积，增加血清中 TPO 水平，减轻脾肿大，减少脾脏和骨髓中巨核细胞的异常增殖。淫羊藿次苷还能下调骨髓 TPO、骨髓母细胞瘤病毒癌基因（MPL）和 p-Stat3 的表达。我们的研究结果表明，淫羊藿次苷可能通过下调 JAK2/Stat3 磷酸化信号通路中 p-Stat3 的表达并调节骨髓 TPO/MPL 代谢，显著改善 ITP 小鼠的健康状况。
