- 作者: I-Ni Hsieh; Anita Shin-Yuan Chang; Che-Ming Teng; Chien-Chih Chen; Chia-Ron Yang
- 作者服務機構: School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Objectives: Natural products have played a significant role in drug discovery and
development. Inflammatory mediators such as inducible nitric oxide synthase (iNOS)
and cyclooxygenase-2 (COX-2) have been suggested to connect with various
inflammatory diseases. In this study, we explored the anti-inflammatory potential of
aciculatin (8-((2R,4S,5S,6R)-tetrahydro-4,5-dihydroxy-6-methyl-2H-pyran-2-yl)-5-
hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one), one of main
components of Chrysopogon aciculatis, by examining its effects on the expression and
activity of iNOS and COX-2 in lipopolysaccharide (LPS)-activated macrophages.
Methods: We used nitrate and prostaglandin E2 (PGE2) assays to examine inhibitory
effect of aciculatin on nitric oxide (NO) and PGE2 levels in LPS-activated mouse
RAW264.7 macrophages and further investigated the mechanisms of aciculatin
suppressed LPS-mediated iNOS/COX-2 expression by western blot, RT-PCR, reporter
gene assay and confocal microscope analysis.
Results: Aciculatin remarkably decreased the LPS (1 μg/mL)-induced mRNA and
protein expression of iNOS and COX-2 as well as their downstream products, NO and
PGE2 respectively, in a concentration-dependent manner (1-10 μM). Such inhibition
was found, via immunoblot analyses, reporter gene assays, and confocal microscope
observations that aciculatin not only acts through significant suppression of LPSinduced
NF-κB activation, an effect highly correlated with its inhibitory effect on LPSinduced
IκB kinase (IKK) activation, IκB degradation, NF-κB phosphorylation,
nuclear translocation and binding of NF-κB to the κB motif of the iNOS and COX-2 promoters, but also suppressed phosphorylation of JNK/p38 mitogen-activated protein
kinases (MAPKs).
Conclusion: Our results demonstrated that aciculatin exerts potent anti-inflammatory
activity through its dual inhibitory effects on iNOS and COX-2 by regulating NF-κB
and JNK/p38 MAPK pathways. - 中文關鍵字: --
- 英文關鍵字: --