Icaritin Provokes Serum Thrombopoietin and Downregulates Thrombopoietin/MPL of the Bone Marrow in a Mouse Model of Immune Thrombocytopenia

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.

Hydrous icaritin nanorods with excellent stability improves the in vitro and in vivo activity against breast cancer

“…Flavonoid compound with presentable antitumor activity is attracting more and more attention, as their various concomitant biological activities beneficial to human health, which may significantly improve the living quality of tumor patients and help them restore their physical power. In our preliminary screening, HICT displayed good growth inhibition against a number of tumor cell lines and immune-enhancing effects (Pan et al, 2007(Pan et al, , 2010Lai et al, 2013;Zhang et al, 2018), but the poor solubility restricted its in vivo drug delivery. In this work, we encapsulated HICT into nanoparticles with high DLC and optimize the formulation to achieve good stability in storage and in various physiological medium, thus suitable to oral or intravenous administration.…”

“…Hydrous icaritin (HICT) is just such a flavonoid compound that can not only effectively inhibit the growth of breast cancer cells (Pan et al, 2007;Pan et al, 2010;Guo et al, 2011;Lai et al, 2013;Wang et al, 2017;Zhang et al, 2018) and cancer stem cells (Guo et al, 2011), but also relieve depression (Pan et al, 2007;Pan et al, 2010). However, like most flavonoids, HICT is water-insoluble, thus difficult to be effectively delivered in vivo, and meanwhile results into low bioavailability and limited effectiveness (Lewin et al, 2013;Guo et al, 2017).…”

Icaritin‐induced immunomodulatory efficacy in advanced hepatitis B virus‐related hepatocellular carcinoma: Immunodynamic biomarkers and overall survival

“…Particularly, advanced HBV‐related HCC patients with poor prognosis characteristics have very limited treatment options, 3,37 or lack of optimal or precision treatment 41,47,48 . Icaritin treatment‐induced anticancer immunomodulation activities through the IL‐6/JAK/STAT3‐associated pathways have been collectively reported in immune‐suppressed MDSCs, 27,30 neutrophils, and platelets (Figure ), 49 and in Th1/Th2 modulation 23 . Here, we further showed the clinical safety and efficacy associated with dynamic changes of immune biomarkers of cytokines, immune checkpoint proteins, and immune cells in advanced HBV‐related HCC with poor prognosis.…”

Icaritin inhibits oxidative stress in murine astrocytes by binding to Orai1 to block store‐operated calcium channel

“…Icaritin (ICT, Figure 1a), the hydrolyzed product of icariin (the major active ingredient of Epimedium sagittatum maxim; Liu & Ye, 2005), has a wide range of established pharmacological effects, including anti‐tumor (Guo et al, 2011), remedy osteoporosis (Zhang et al, 2009), resist immune thrombocytopenia (Sun, Yang, Wang, et al, 2018; Zhang et al, 2018), and improve bone marrow suppression caused by chemotherapy drugs (Sun, Yang, Pan, et al, 2018). In addition, ICT also exhibits an immunoregulative effect on macrophages by blocking phosphorylation of p38 and JNK2 (Lai et al, 2013).…”