Apigenin from Croton betulaster Müll restores the immune profile of microglia against glioma cells

Abstract

The flavonoid apigenin, extracted from the Brazilian plant Croton betulaster Müll. has demonstrated the ability to inhibit proliferation, induce differentiation, and modify the inflammatory profile of glioma cells. The aim of the present study was to evaluate the effect of apigenin on chemotaxis and regulation of inflammatory cytokines of microglia cells and these impacts on glioma cell growth. In cultures of isolated rat microglia, it was observed that apigenin induced changes in Iba1‐positive cells to an ameboid phenotype, associated to an increase in the expression of the activated M1 profile marker OX‐42 and iNOS and a reduction in the expression of the M2 profile marker CD206. Besides, apigenin modulated the tumor necrosis factor and IL‐10 release by microglia. Treatment of C6 glioma cells with conditioned medium of microglia treated with apigenin‐induced reduction of tumor migration and viability, associated with significant reduction in IL‐6 levels. On the other hand, treatment of C6 cells with apigenin‐induced microglia chemotaxis to glioma in vitro. Moreover, apigenin treatment of microglia/C6 co‐cultures induced preferentially reduction in the viability of C6 cells and increased microglia‐activated phenotype, associated with a change in the balance of TNF/IL‐10 levels. Together, these results demonstrated that the flavonoid apigenin restores the immune profile of microglia against glioma cells.