title: 4,7-Dimethoxy-5-methyl-1,3-benzodioxole from Antrodia camphorata inhibits LPS-induced inflammation via suppression of NF-κB and induction HO-1 in RAW264.7 cells.
abstract: Several benzenoid compounds have been isolated from Antrodia camphorata are known to have excellent anti-inflammatory activity. In this study, we investigated the anti-inflammatory potential of 4,7-dimethoxy-5-methyl-1,3-benzodioxole (DMB), one of the major benzenoid compounds isolated from the mycelia of A. camphorata. DMB significantly decreased the LPS-induced production of pro-inflammatory molecules, such as nitric oxide (NO), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in RAW264.7 cells. In addition, DMB suppressed the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose dependent manner. Moreover, DMB significantly suppressed LPS-induced nuclear translocation of nuclear factor-κB (NF-κB), and this inhibition was found to be associated with decreases in the phosphorylation and degradation of its inhibitor, inhibitory κB-α (IκB-α). Moreover, we found that DMB markedly inhibited the protein expression level of Toll-like receptor 4 (TLR4). Furthermore, treatment with DMB significantly increased hemoxygenase-1 (HO-1) expression in RAW264.7 cells, which is further confirmed by hemin, a HO-1 enhancer, significantly attenuated the LPS-induced pro-inflammatory molecules and iNOS and TLR4 protein levels. Taken together, the present study suggests that DMB may have therapeutic potential for the treatment of inflammatory diseases.
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan.
authors.forename: Pei-Hsin
authors.initials: PH
authors.lastname: Shie
authors.affiliation: Department of Forestry, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Sheng-Yang
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Plant Industry, National Pingtung University of Science and Technology, Pingtung 902, Taiwan. Electronic address: layhl@mail.npust.edu.tw.
authors.forename: Horng-Liang
authors.initials: HL
authors.lastname: Lay
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan. Electronic address: gjhuang@mail.cmu.edu.tw.
authors.forename: Guan-Jhong
authors.initials: GJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D055491:Antrodia / Q000276:immunology*; D052117:Benzodioxoles / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D000067996:RAW 264.7 Cells; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C574078:4,7-dimethoxy-5-methyl-1,3-benzodioxole; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052117:Benzodioxoles; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: 4,7-Dimethoxy-5-methyl-1,3-benzodioxole; Anti-inflammation; Antrodia camphorata; HO-1; NF-κB