Abstract

Immunomodulatory drugs are widely used for the treatment of inflammatory and immune-mediated conditions; however, their prolonged use is usually associated with the appearance of side effects and many immune disorders continuous without a suitable treatment. Natural products are an important source of therapies to a variety of illnesses. The present work investigated the immunomodulatory activity of a hexane extract and isolated compounds from Annona vepretorum Mart. Roots of A. vepretorum were used to produce a hexane extract, which was fractionated to obtain three diterpenes belonging to ent-kaurane series. The cytotoxicity of samples was determined using J774 macrophages. The immunomodulatory activity of natural products on macrophages activated with LPS and IFN-γ was determined by evaluation of nitric oxide (NO) and cytokine production. The effects of samples on lymphocyte proliferation were evaluated using splenocyte cultures stimulated with concanavalin A or in mixed lymphocyte reaction (MLR), by assessment of 3H-thymidine incorporation. The production of IL-2 and IFN-γ by lymphocytes was evaluated by ELISA. The effects of extract on the cell cycle progression of lymphocytes were evaluated by flow cytometry. The extract had low cytotoxicity and was able to modulate macrophages and lymphocytes in atoxic concentrations. AVHR (A. vepretorum hexane extract) significantly decreased NO, TNF-α, IL-1β and IL-6 production by activated macrophages. The extract also inhibited lymphocyte proliferation and IL-2 and IFN-γ production by activated splenocytes. In a concentration-dependent manner, the hexane extract arrested cell cycle in G0/G1 phase, accompanied by an increase of cells in PreG1 phase. Isolated compounds also were capable for modulates macrophage activation and lymphocyte function. The present findings demonstrate a potent immunomodulatory activity of hexane extract from roots of A. vepretorum.

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