p-Cymene Modulates In Vitro and In Vivo Cytokine Production by Inhibiting MAPK and NF-κB Activation

The present study was designed to investigate the effects of p-cymene on lipopolysaccharide (LPS)-induced inflammatory cytokine production both in vitro and in vivo. The production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and interleukin-10 (IL-10) in LPS-stimulated RAW 264.7 cells and C57BL/6 mice was evaluated by sandwich ELISA. Meanwhile, the mRNA levels of cytokine genes were examined in vitro by semiquantitative RTPCR. In a further study, we analyzed the activation of nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) signaling pathways by western blotting. We found that p-cymene significantly regulated TNF-alpha, IL-1 beta, and IL-6 production in LPS-stimulated RAW 264.7 cells. Furthermore, the levels of relative mRNAs were also found to be downregulated. In in vivo trail, p-cymene markedly suppressed the production of TNF-alpha and IL-1 beta and increased IL-10 secretion. We also found that p-cymene inhibited LPS-induced activation of extracellular signal receptor-activated kinase 1/2, p38, c-Jun N-terminal kinase, and I kappa B alpha. These results suggest that p-cymene may have a potential anti-inflammatory action on cytokine production by blocking NF-kappa B and MAPK signaling pathways.