Anti-inflammatory effects of magnolol and honokiol are mediated through inhibition of the downstream pathway of MEKK-1 in NF-κB activation signaling

Propionibacterium acnes, an anaerobic pathogen, plays an important role in the pathogenesis of acne and seems to initiate the inflammatory process by producing proinflammatory cytokines. In order to demonstrate the anti-inflammatory effects and action mechanisms of magnolol and honokiol, several methods were employed. Through DPPH and SOD activity assays, we found that although both magnolol and honokiol have antioxidant activities, honokiol has relatively stronger antioxidant activities than magnolol {[for DPPH assay, % of DPPH bleaching of magnolol and honokiol (500 MM magnolol: 19.8%; 500 mu M honokiol: 67.3%)]; [for SOD assay, SOD activity (200 mu M magnolol: 53.4%; 200 mu M honokiol: 64.3%)]}. Moreover, the production of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) induced by P. acnes in THP-1 cells, a human monocytic cell line, was reduced by magnolol and honokiol {[for IL-8 (10 mu M magnolol: 42.7% inhibition; 10 MM honokiol: 51.4% inhibition)]; [for TNF-alpha (10 PM magnolol: 20.3% inhibition; 10 mu M honokiol: 39.0% inhibition)]}. Cyclooxygenase-2 (Cox-2) activity was also suppressed by them [(15 mu M magnolol: 45.8% inhibition), (15 mu M honokiol: 66.3% inhibition)]. Using a nuclear factor-kappa B (NF-kappa B) luciferase reporter assay system and Western analysis, we identified that magnolol and honokiol exert their anti-inflammatory effects by inhibiting the NF-kappa B element, which exists in Cox-2, IL-8, and TNF-alpha promoters [(15 mu M magnolol: 44.8% inhibition), (15 mu M honokiol: 42.3% inhibition)]. Of particular note is that magnolol and honokiol operate downstream of the MEKK-1 molecule. Together with their previously known antibacterial activity against P. acnes and based on these results, we suggest that magnolol and honokiol may be introduced as possible acne-mitigating agents.