期刊
DRUG DESIGN DEVELOPMENT AND THERAPY
卷 10, 期 -, 页码 1829-1835出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S104602
关键词
Anti-inflammatory effects; guggulsterone; lipopolysaccharides; NF-kappa B; IL-1 beta; TNF-alpha
资金
- Xiamen Medical College
- Young Foundation of Fujian Provincial Health Department [2010-2-68]
- Young Talent Foundation of Fujian Provincial Health Department [2013-ZQN-ZD-31]
- Promotion Program for Young and Middle-aged Teacher in Science and Technology Research of Huaqiao University [ZQN-YX205]
The present study was aimed to investigate the effects of guggulsterone (GS) on proinflammatory responses as well as the underlying molecular mechanisms in macrophage upon lipopolysaccharide (LPS) stimulation. Effects of GS on viability of Raw264.7 cells were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Real-time polymerase chain reaction (PCR) was employed to examine the mRNA expression of cytokines, including interleukin 1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS). Phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (p38), and inhibitor of nuclear factor kappaB (I kappa B) were determined using immunoblotting. The results revealed that GS was not toxic to Raw264.7 cells at designated concentrations. We demonstrated that GS significantly suppressed the elevated mRNA expression of proinflammatory cytokines, including IL-1 beta, TNF-alpha, and iNOS in a dose-dependent manner. GS treatment reduced the level of I kappa B phosphorylation in LPS-stimulated macrophages in a dose-dependent manner. Use of BAY 11-7082, an inhibitor of nuclear factor-kappaB (NF-kappa B), led to significantly suppressing effects on IL-1 beta and TNF-alpha expression similar as that of GS-treated cells. Our findings suggest that GS possesses anti-inflammatory activity, which may be attributed to downregulation of iNOS and inhibition of NF-kappa B activity in LPS-stimulated Raw264.7 cells.
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