Stellera chamaejasme Methanolic Extract Attenuates Nitric Oxide Production and Enhances Heme Oxygenase 1 Expression in Murine Macrophages

Abstract

Stellera chamaejasme has been used in Chinese folk medicine against skin diseases, chronic tracheitis, and tuberculosis. However, the medicinal value of this plant has not been verified experimentally and there exists paucity of data as to the anti-inflammatory and anti-oxidant properties. Therefore, we explored that Stellera chamaejasme methanolic extract (SCME) potently inhibited nitric oxide (NO) release in LPS stimulated RAW264.7 cells. SCME (1-10 mg/ml) also down-regulated inducible nitric oxide synthase (iNOS) mRNA and protein expressions, while it markedly enhanced HO-1 expression. Moreover, SCME alone induced the phosphorylations of ERK1/2, JNK, p38 MAPK, Akt, and IkB-a. Likewise, SCME increased the nuclear levels of phosphorylated Nrf-2, c-Fos, c-Jun and ATF-2 transcription factors. On the other hand, inhibitors of ERK1/2 (PD98059), PI-3K/Akt (LY294002), protein kinase (PK)-A (H-89), PKC (H-7) and NF-kB (BAY117082) attenuated SCME induced HO-1 expression, suggesting the involvement of these pathways. Taken together, we reported for the first time that SCME potently inhibited NO production whereas it up-regulated HO-1 expression at low concentrations. Thus, this extract could be a potential source of natural compounds that may reduce the overwhelming inflammation and cellular oxidation.