Suppression of Inducible Nitric Oxide Synthase Expression by Nyasol and Broussonin A, Two Phenolic Compounds from Anemarrhena asphodeloides, through NF-[kappa]B Transcriptional Regulation in vitro and in vivo

• Published in: Chemistry & biodiversity 2014-05, Vol.11 (5), p.749
• Main Authors: JinLee, Eun, Chung, Hwa-Jin, Pyee, Yuna, Hong, Ji-Young, JoungYoun, Ui, Seo, Eun-Kyoung, KookLee, Sang
• Format: Article
• Language: English
• Subjects: Chinese medicine; Nitric oxide; Rodents
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.201400003

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-1[beta] (IL-1[beta]) and interferon-[beta] (IFN-[beta]). They also inhibited the transcriptional activity of NF-[kappa]B and degradation of I[kappa]B-[alpha], 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-[kappa]B 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. [PUBLICATION ABSTRACT]