title: Ethanol extract of Poria cocos reduces the production of inflammatory mediators by suppressing the NF-kappaB signaling pathway in lipopolysaccharide-stimulated RAW 264.7 macrophages.
abstract: BACKGROUND
  Poria cocos Wolf, a medicinal fungus, is widely used in traditional medicines in East Asian countries owing to its various therapeutic potentials. Although several studies have demonstrated the anti-inflammatory activity of this fungus, its underlying mechanisms have not yet been clearly defined.
  
  
  METHODS
  In the present study, we have demonstrated the anti-inflammatory effects of ethanol extract of P. cocos (EEPC) in lipopolysaccaride (LPS)-stimulated RAW 264.7 macrophages. As inflammatory parameters, the productions of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β and tumor necrosis factor (TNF)-α were evaluated. We also examined the EEPC's effect on the nuclear factor-kappaB (NF-κB) signaling pathway.
  
  
  RESULTS
  Our results indicated that EEPC exhibits a potent inhibitory effect on NO production and inhibits PGE2 release in LPS-induced macrophages without affecting cell viability. EEPC also significantly attenuated LPS-induced secretion of inflammatory cytokines IL-1β and TNF-α. Additionally, LPS-induced expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, IL-1β, and TNF-α was decreased by pre-treatment with EEPC at the transcriptional level. Moreover, EEPC clearly inhibited LPS-induced nuclear translocation of NF-κB p65 subunits, which correlated with EEPC's inhibitory effects on inhibitor kappaB (IκB) degradation. Moreover, EEPC clearly suppressed the LPS-induced DNA-binding activity of NF-κB, as well as the nuclear translocation of the NF-κB p65, which correlated with EEPC's inhibitory effects on inhibitor kappaB (IκB) degradation.
  
  
  CONCLUSIONS
  Taken together, our data indicates that EEPC targets the inflammatory response of macrophages via inhibition of iNOS, COX-2, IL-1β, and TNF-α through inactivation of the NF-κB signaling pathway, supporting the pharmacological basis of P. cocos as a traditional herbal medicine for treatment of inflammation and its associated disorders.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Jeong
authors.forename: Hye Hyeon
authors.initials: HH
authors.lastname: Lee
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Han
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Su Hyun
authors.initials: SH
authors.lastname: Hong
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-052, Republic of Korea. choiyh@deu.ac.kr.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D008517:Phytotherapy; D055441:Poria; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone