title: Anti-inflammatory effects of magnolol and honokiol are mediated through inhibition of the downstream pathway of MEKK-1 in NF-kappaB activation signaling.
abstract: 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 microM magnolol: 19.8%; 500 microM honokiol: 67.3%)]; [for SOD assay, SOD activity (200 microM magnolol: 53.4%; 200 microM 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 microM magnolol: 42.7% inhibition; 10 microM honokiol: 51.4% inhibition)]; [for TNF-alpha (10 microM magnolol: 20.3% inhibition; 10 microM honokiol: 39.0% inhibition)]}. Cyclooxygenase-2 (Cox-2) activity was also suppressed by them [(15 microM magnolol: 45.8% inhibition), (15 microM honokiol: 66.3% inhibition)]. Using a nuclear factor-kappaB (NF-kappaB) luciferase reporter assay system and Western analysis, we identified that magnolol and honokiol exert their anti-inflammatory effects by inhibiting the NF-kappaB element, which exists in Cox-2, IL-8, and TNF-alpha promoters [(15 microM magnolol: 44.8% inhibition), (15 microM 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.
authors.affiliation: Biospectrum Life Science Institute, Yongin-city, Kyunggi-do, Korea.
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.forename: Eunsun
authors.initials: E
authors.lastname: Jung
authors.forename: Junho
authors.initials: J
authors.lastname: Park
authors.forename: Kwangseon
authors.initials: K
authors.lastname: Jung
authors.forename: Sangyeop
authors.initials: S
authors.lastname: Lee
authors.forename: Sungtaek
authors.initials: S
authors.lastname: Hong
authors.forename: Jinil
authors.initials: J
authors.lastname: Park
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Park
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.forename: Sanghee
authors.initials: S
authors.lastname: Park
authors.forename: Deokhoon
authors.initials: D
authors.lastname: Park
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D017705:Lignans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D048728:MAP Kinase Kinase Kinase 1 / Q000187:drug effects*; D031566:Magnolia; D008826:Microbial Sensitivity Tests; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects*; D008517:Phytotherapy; D010851:Picrates / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011425:Propionibacterium acnes / Q000187:drug effects; D013482:Superoxide Dismutase / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001713:Biphenyl Compounds; D016207:Cytokines; D016209:Interleukin-8; D017705:Lignans; D048728:MAP Kinase Kinase Kinase 1; D016328:NF-kappa B; D010851:Picrates; D010936:Plant Extracts; D013482:Superoxide Dismutase; D014409:Tumor Necrosis Factor-alpha; C005498:magnolol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C004931:1,1-diphenyl-2-picrylhydrazyl