title: Diosgenin inhibits macrophage-derived inflammatory mediators through downregulation of CK2, JNK, NF-kappaB and AP-1 activation.
abstract: Diosgenin is a precursor of steroid hormones, which can be found in several plant species. Diosgenin has been shown to have a variety of biological activities including anti-inflammatory activity, but through a mechanism that is unclear. Especially, the effect of this agent on macrophage function has not been characterized in detail. In the present study, we examined the effects of diosgenin on the production of inflammatory mediators in lipopolysaccharide (LPS)/interferon gamma (IFN-gamma)-activated murine macrophage. Macrophages pre-exposed to diosgenin (0.1-10 microM) were stimulated with LPS/IFN-gamma. Pretreatment with diosgenin resulted in the inhibition of NO production and inducible nitric oxide synthase (iNOS) protein and mRNA expression in a concentration-dependent manner. In addition, diosgenin inhibits production of reactive oxygen species (ROS), interleukin-1 (IL-1), and IL-6, but not that of tumor necrosis factor-alpha (TNF-alpha). Inhibition of these inflammatory mediators appears to be at the transcriptional level, since diosgenin decreased LPS/IFN-gamma-induced NF-kappaB and AP-1 activity. Diosgenin blocked CK2 activation and phosphorylation of c-Jun NH(2)-terminal kinase (JNK), but not that of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 (ERK 1/2). These results indicate that the inhibition of these signaling molecules expression was correlated with the reduced production of inflammatory mediators in macrophages. Taken together the present data suggest that diosgenin reduces the production of inflammatory meditators by inhibiting LPS/IFN-gamma-triggered CK2, JNK, NF-kappaB and AP-1 activation, thereby implicating a mechanism by which diosgenin may exert its immunosuppressive effects.
authors.affiliation: Devision of Immunopharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do, 440-746, Republic of Korea.
authors.forename: Da-Hye
authors.initials: DH
authors.lastname: Jung
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Byun
authors.forename: Yoon-Moon
authors.initials: YM
authors.lastname: Park
authors.forename: Tae-Wan
authors.initials: TW
authors.lastname: Kim
authors.forename: Byung-Oh
authors.initials: BO
authors.lastname: Kim
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Um
authors.forename: Suhkneung
authors.initials: S
authors.lastname: Pyo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D047390:Casein Kinase II / Q000032:analysis / Q000037:antagonists & inhibitors; D018929:Cell Culture Techniques; D004144:Diosgenin / Q000494:pharmacology*; D015536:Down-Regulation; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D048031:JNK Mitogen-Activated Protein Kinases / Q000032:analysis / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D047390:Casein Kinase II; D048031:JNK Mitogen-Activated Protein Kinases; D004144:Diosgenin