Abstract

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.

Highlights

  • Immune thrombocytopenia (ITP) is known as autoimmune thrombocytopenic purpura or idiopathic thrombocytopenic purpura, and it is a common acquired autoimmune bleeding disorder

  • PLT and PCT in the low, middle, and high doses of icaritin groups were significantly increased. These results demonstrate that icariin significantly increased platelet counts in the peripheral blood of ITP mice and improved the symptoms of thrombocytopenia

  • Continuous injection of Guinea pig anti-mouse platelet antiserum (GP-antiplatelet serum (APS)) resulted in greater platelet destruction in peripheral blood and increased MPV (P < 0 001), and low doses of icaritin reduced MPV (P < 0 05)

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Summary

Introduction

Immune thrombocytopenia (ITP) is known as autoimmune thrombocytopenic purpura or idiopathic thrombocytopenic purpura, and it is a common acquired autoimmune bleeding disorder. Decreased peripheral platelet counts and bleeding are its primary clinical manifestations [1]. Autoantibody-mediated humoral immunity-induced platelet destruction is important in the pathogenesis of this disease [2]. ITP accounts for approximately 1/3 of the bleeding disorders. The incidence of ITP is approximately 2 to 4 cases per 100,000 adults [3]. People over the age of 60 years are the high-incidence population for this disease, which causes extensive skin and mucous membrane bleeding and epistaxis. Severe cases cause visceral and intracranial hemorrhages, which endanger life [4]

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