The effects of Calophyllum brasiliense leaves extract and isolated compound amentoflavone: implications in the resolution of inflammation

Calophyllum brasiliense is employed in folk medicine as an analgesic and to treat inflammation. This study aimed to evaluate the anti-inflammatory effect of C. brasiliense leaves' methanol extract, fractions, and the isolated compound amentoflavone. In vitro fMLP-induced neutrophil chemotaxis and LPS-induced inflammatory mediator levels were assessed in neutrophils or macrophages treated or not with different concentrations of C. brasiliense extract, its fractions or amentoflavone. Their effects on inflammation resolution was assessed by evaluating the efferocytosis. The extract and its fractions (DFCB, AFCB, and MFCB) impaired neutrophil migration stimulated by the chemotactic mediator fMLP and its ability to produce and/or to release cytokines (TNF and IL-6) and NO. The increase of the apoptotic neutrophil efferocytosis was observed for cells treated with the ethyl acetate and methanol fractions, accompanied by the enhanced IL-10 levels in the supernatant and the decrease of TNF, as well. Amentoflavone, present in high concentration in ethyl acetate fraction, reduced the inflammatory mediators levels in LPS-stimulated macrophages, impaired the neutrophil chemotaxis, and enhanced the efferocytosis. The obtained data demonstrate that C. brasiliense extract presented anti-inflammatory effects by modulating neutrophil migration/activation, macrophage-dependent efferocytosis, and inflammatory mediator release, effects at least partly addressed to amentoflavone content.