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Br J Pharmacol. 2006 May;148(2):216-25.

Anti-inflammatory effect of buddlejasaponin IV through the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via the NF-kappaB inactivation.

Author information

1
Department of Biochemistry, College of Pharmacy, Kyung-Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul 130-701, South Korea.

Abstract

Buddlejasaponin IV isolated from Pleurospermum kamtschatidum is an anti-inflammatory compound that inhibits NO, PGE(2) and TNF-alpha production. Here, we studied the mode of action of this compound. Buddlejasaponin IV (2.5-10 microM) reduced lipopolysaccaride (LPS (1 microg ml(-1)))-induced levels of iNOS and COX-2 at the protein levels, and iNOS, COX-2, TNF-alpha, interleukin (IL)-1beta and IL-6 mRNA expression in RAW 264.7 macrophages in a concentration-dependent manner, as determined by Western blotting and RT-PCR, respectively. Buddlejasaponin IV inhibited the LPS-induced activation of nuclear factor-kappaB (NF-kappaB), a transcription factor necessary for proinflammatory mediators, iNOS, COX-2, TNF-alpha, IL-1beta and IL-6 expression. This effect was accompanied by a parallel reduction in IkappaB-alpha degradation and phosphorylation, and by the nuclear translocation of the NF-kappaB p65 subunit. The effects of buddlejasaponin IV on acute phase inflammation were studied on serotonin- and carrageenan-induced paw edema. The antiedematous effect of buddlejasaponin IV was compared with 10 mg kg(-1) of indomethacin p.o. Maximum inhibitions of 26 and 41% were noted at a dose of 20 mg kg(-1) for serotonin- and carrageenan-induced paw edema, respectively. The analgesic effect of buddlejasaponin IV was evaluated using acetic acid-induced writhing and hot-plate tests. Buddlejasaponin IV (10 and 20 mg kg(-1), p.o.) was found to have a marked analgesic effect in both models. These results suggest that the inhibitions of the expressions of iNOS, COX-2, TNF-alpha, IL-1beta and IL-6 by blocking NF-kappaB activation, are responsible for the anti-inflammatory effects of buddlejasaponin IV isolated from P. kamtschatidum.

PMID:
16520738
PMCID:
PMC1617058
DOI:
10.1038/sj.bjp.0706718
[Indexed for MEDLINE]
Free PMC Article

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