Icariin protects bone marrow mesenchymal stem cells in aplastic anemia by targeting MAPK pathway.

Abstract

Icariin, the main pharmacological active flavonoid extracted from Epimedi herba, can regulate cellular processes in diverse diseases. The aim of this study was to explore the effects and mechanisms of icariin on proliferation and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) in aplastic anemia (AA). Bone marrow mesenchymal stem cells were isolated from posterior tibias and femurs of AA rats that were induced by benzene and cyclophosphamide and gavaged with icariin. The isolated BMSCs were characterized morphologically and immunologically by positive markers (CD29 and CD90) and negative markers (CD34 and CD45). CCK-8 assay was performed to examine the BMSCs proliferation. Cell apoptosis and cell cycle were detected by flow cytometry. Oil red O staining was carried out to evaluate the adipogenesis of BMSCs. The mRNA expression of PPARγ, C/EBP-α, and FABP4 was measured by qRT-PCR. The protein levels of p-p38/p38, p-JNK/JNK, p-ERK/ERK, PPARγ, C/EBP-α, and FABP4 were detected using Western blotting. Icariin promoted the proliferation of BMSCs from AA rats in a dose-dependent manner. The protein levels of p-p38/p38, p-JNK/JNK, and p-ERK/ERK were downregulated in BMSCs from AA rats after icariin treatment. Icariin inhibited the apoptosis and arrested cell cycle at G/S phase of BMSCs from AA rats. The adipogenesis of BMSCs from AA rats was also suppressed after icariin treatment. However, the effects of icariin on BMSCs were weakened by p38 agonist addition. Icariin promoted the proliferation and inhibited the apoptosis and adipogenesis of BMSCs in AA by suppressing MAPK pathway.