Flavonoids from Radix Tetrastigmae inhibit TLR4/MD-2 mediated JNK and NF-κB pathway with anti-inflammatory properties

• Published in: Cytokine (Philadelphia, Pa.) Vol. 84; pp. 29 - 36
• Main Authors: Liu, Dandan, Cao, Gang, Han, Likai, Ye, Yilu, SiMa, Yuhan, Ge, Weihong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2016
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Cell Line; Flavonoids - pharmacology; Inflammation - drug therapy; Inflammation - metabolism; JNK; Lipopolysaccharides - pharmacology; Lymphocyte Antigen 96 - metabolism; Macrophages - drug effects; Macrophages - metabolism; MAP Kinase Signaling System - drug effects; MD-2; Mice; NF-kappa B - metabolism; NF-κB; Phosphorylation - drug effects; Plant Roots - chemistry; Radix Tetrastigmae flavonoids; RAW 264.7 Cells; Signal Transduction - drug effects; TLR4; Toll-Like Receptor 4 - metabolism; Up-Regulation - drug effects; NF-κB; Radix Tetrastigmae flavonoids; JNK; MD-2; RTFs; TLR4; LPS; MAPKs
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2015.08.003

•RTFs inhibit LPS-induced inflammation in macrophages.•RTFs decrease pro-inflammatory factors production.•RTFs increase anti-inflammatory cytokines secretion.•RTFs block TLR4/MD-2 mediated pathway.•RTFs reduce JNK phosphorylation and NF-κB activity. Radix Tetrastigmae (RT) has immunomodulatory activity, particularly on inflammation and the flavonoids from RT (RTFs) are one of the main components. In this study, we detected the anti-inflammation potential of RTFs in LPS-induced RAW264.7 cells and tried to uncover the underlying mechanism. Results demonstrated that RTFs (10–160μg/ml) treatment significantly decreased LPS-induced production of pro-inflammatory mediators, including NO, IL-1β, TNF-α, IL-6, IL-12p40, sTNF-R1 and increased anti-inflammatory cytokine IL-10 expression in macrophages in a dose-dependent manner. Molecular research showed the up-regulated expression of TLR4, MD-2, MyD88 and TLR4/MD-2 complex induced by LPS were attenuated after RTFs treatment. Furthermore, phosphorylation and activity of JNK and NF-κB, two important downstream signaling molecules of TLR4/MD-2 pathway, were also changed along with TLR4/MD-2 complex. But no significant phosphorylation was observed on p38 and ERK. In conclusion, RTFs contribute to the regulation of LPS-induced inflammatory response in RAW264.7 cells through TLR4/MD-2 mediated NF-κB and JNK pathway. It may be a potential choice for the treatment of inflammation diseases.