Chlojaponilactone B from Chloranthus japonicus: Suppression of Inflammatory Responses via Inhibition of the NF-κB Signaling Pathway

Autor: Yan-Qiong Guo, Xue Xue, Jing-jun Zhao, Long-Ping Zhu, Qin Liu, Depo Yang, Zhimin Zhao, Sheng Yin
Rok vydání: 2016
Předmět:
Lipopolysaccharides
0301 basic medicine
Lipopolysaccharide
Chloranthus japonicus
Transcription Factor RelA
Anti-Inflammatory Agents
Nitric Oxide Synthase Type II
Pharmaceutical Science
Biology
Nitric Oxide
01 natural sciences
Analytical Chemistry
Nitric oxide
Mice
03 medical and health sciences
chemistry.chemical_compound
Drug Discovery
medicine
Animals
Phosphorylation
Inflammation
Pharmacology
Molecular Structure
Interleukin-6
Tumor Necrosis Factor-alpha
010405 organic chemistry
Macrophages
Organic Chemistry
NF-kappa B
medicine.disease
0104 chemical sciences
Cell biology
IκBα
030104 developmental biology
Complementary and alternative medicine
chemistry
Biochemistry
Cyclooxygenase 2
Cytokines
Molecular Medicine
Inflammation Mediators
Signal transduction
Sesquiterpenes
Infiltration (medical)
Signal Transduction
Zdroj: Journal of Natural Products. 79:2257-2263
ISSN: 1520-6025
0163-3864
DOI: 10.1021/acs.jnatprod.6b00355
Popis: Bioassay-guided fractionation of an ethanolic extract of Chloranthus japonicus led to the isolation of the known lindenane-type sesquiterpenoid chlojaponilactone B (1). This compound exhibited pronounced inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Further anti-inflammatory assays showed that 1 suppressed the levels of some key inflammation mediators, such as iNOS, TNF-α, and IL-6, in a dose-dependent manner, and reduced the ear thickness and neutrophil infiltration in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mice. A mechanistic study revealed that compound 1 exerted its anti-inflammatory effects via the suppression of the NF-κB signaling pathway, which inhibited NF-κB-dependent transcriptional activity, IκBα phosphorylation, and p65 nuclear translocation. In contrast, chlojaponilactone B (1) was found to exert little influence on the MAPK signaling pathway.
Databáze: OpenAIRE