期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 17, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/ijms17111938
关键词
Sarcandra glabra; sesquiterpene; chloranthalactone B; inflammation
资金
- National Natural Science Foundation of China [31600281]
- Natural Science Foundation of the Higher Education Institutions of Jiangsu Province [14KJB550002, 15KJB550001]
- Natural Science Foundation of Jiangsu Province [BK20150414]
- Top-notch Academic Programs Project of Jiangsu Higher Education Institutions [PPZY2015A018]
- QingLan Project of Jiangsu Province
Chloranthalactone B (CTB), a lindenane-type sesquiterpenoid, was obtained from the Chinese medicinal herb Sarcandra glabra, which is frequently used as a remedy for inflammatory diseases. However, the anti-inflammatory mechanisms of CTB have not been fully elucidated. In this study, we investigated the molecular mechanisms underlying these effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. CTB strongly inhibited the production of nitric oxide and pro-inflammatory mediators such as prostaglandin E2, tumor necrosis factor beta (TNF-beta), interleukin-1 beta (IL-1 beta), and IL-6 in RAW264.7 cells stimulated with LPS. A reverse-transcription polymerase chain reaction assay andWestern blot further confirmed that CTB inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, TNF-beta, and IL-1 beta at the transcriptional level, and decreased the luciferase activities of activator protein (AP)-1 reporter promoters. These data suggest that inhibition occurred at the transcriptional level. In addition, CTB blocked the activation of p38 mitogen-activated protein kinase (MAPK) but not c-Jun N-terminal kinase or extracellular signal-regulated kinase 1/2. Furthermore, CTB suppressed the phosphorylation of MKK3/6 by targeting the binding sites via formation of hydrogen bonds. Our findings clearly show that CTB inhibits the production of inflammatory mediators by inhibiting the AP-1 and p38 MAPK pathways. Therefore, CTB could potentially be used as an anti-inflammatory agent.
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