Suppression of inducible nitric oxide synthase expression by nyasol and broussonin A, two phenolic compounds from Anemarrhena asphodeloides, through NF-κB transcriptional regulation in vitro and in vivo.
Anemarrhena asphodeloides is widely used in traditional Chinese medicine, and is known to possess antidiabetic and anti-inflammatory properties. Because inducible nitric oxide synthase (iNOS) plays an important role in inflammation, we investigated the inhibitory effects of two known phenolic compounds, nyasol (1) and broussonin A (2), from A. asphodeloides, on iNOS and its plausible mechanism of action. Compounds 1 and 2 exhibited inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Compounds 1 and 2 also suppressed the expressions of iNOS protein and mRNA. Moreover, compounds 1 and 2 suppressed the expression of inflammatory cytokines such as interleukin-1β (IL-1β) and interferon-β (IFN-β). They also inhibited the transcriptional activity of NF-κB and degradation of IκB-α, as well as the activation of Akt and ERK in LPS-stimulated RAW 264.7 cells. In in vivo animal model, compounds 1 and 2 significantly inhibited TPA-induced mouse ear edema. These results suggest that 1 and 2 suppress LPS-stimulated iNOS expression at the transcriptional level through modulating NF-κB and down-regulation of the Akt and ERK signaling pathways. Taken together, these findings indicate that the suppressive effects of 1 and 2 on iNOS expression might provide one possible mechanism for their anti-inflammatory activities.
College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
Eun
E
Jin Lee
Hwa-Jin
HJ
Chung
Yuna
Y
Pyee
Ji-Young
JY
Hong
Ui
U
Joung Youn
Eun-Kyoung
EK
Seo
Sang
S
Kook Lee
D031403:Anemarrhena / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D020672:I-kappa B Proteins / Q000235:genetics* / Q000276:immunology; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000276:immunology; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D015533:Transcriptional Activation / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D017705:Lignans; D008070:Lipopolysaccharides; C000606205:Nfkbia protein, mouse; D010636:Phenols; C524287:broussonin A; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; C109393:nyasol; D052247:Nitric Oxide Synthase Type II
Anti-inflammatory activity; Broussonin A; Inducible nitric oxide synthase (iNOS); NF-κB; Nyasol