Immunostimulatory Activities of Theobromine on Macrophages via the Activation of MAPK and NF-κB Signaling Pathways

Theobromine is mainly found in plant foods, such as tea; the primary source of theobromine is the seeds of the Theobroma cacao tree. Theobromine is an alkaloid belonging to the methylxanthine class of drugs, and it is similar to theophylline and caffeine. Theobromine is known for its efficacy and role in health and disorder prevention. We evaluated the effects of theobromine on macrophage function, including the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB). Theobromine significantly stimulated the production of nitric oxide (NO) and prostaglandin E2 through immune responses, which relate to the increased expression of inducible nitric oxide synthase and cyclooxygenase-2. Additionally, theobromine increased the production of inflammatory cytokines, including tumor necrosis factor-α and interleukin-6 in macrophages. Additionally, theobromine induced the translocation and activity of NF-κB in a concentration-dependent manner. Consistent with these results, the phosphorylation level of MAPKs was increased in theobromine-stimulated macrophages. Collectively, these data revealed that theobromine acts as an immune response stimulator via the NF-κB and MAPKs signaling pathways. Thus, theobromine might have protective effects against inflammatory disorders.