title: Flavonoids from Radix Tetrastigmae inhibit TLR4/MD-2 mediated JNK and NF-κB pathway with anti-inflammatory properties.
abstract: 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.
authors.affiliation: Pharmaceutical College, Zhejiang Chinese Medical University, 546 Binwen Road, Hangzhou 310053, China; Department of Basic medicine, Hangzhou Medical College, 481 Binwen Road, Hangzhou 310053, China. Electronic address: 7559220@qq.com.
authors.forename: Dandan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Pharmaceutical College, Zhejiang Chinese Medical University, 546 Binwen Road, Hangzhou 310053, China. Electronic address: caogang33@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Cao
authors.affiliation: Pathological Department, People's Hospital of Zhejiang Province, 158 Shangtang Road, Hangzhou 310014, China. Electronic address: hanlikai@vip.qq.com.
authors.forename: Likai
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Basic medicine, Hangzhou Medical College, 481 Binwen Road, Hangzhou 310053, China. Electronic address: 307952548@qq.com.
authors.forename: Yilu
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Hangzhou Xuejun High School, 188 Wensan Road, Hangzhou 310012, China. Electronic address: 76440698@qq.com.
authors.forename: Yuhan
authors.initials: Y
authors.lastname: SiMa
authors.affiliation: Pharmaceutical College, Zhejiang Chinese Medical University, 546 Binwen Road, Hangzhou 310053, China. Electronic address: geweihong@hotmail.com.
authors.forename: Weihong
authors.initials: W
authors.lastname: Ge
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D005419:Flavonoids / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051218:Lymphocyte Antigen 96 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D018517:Plant Roots / Q000737:chemistry; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D008070:Lipopolysaccharides; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: JNK; MD-2; NF-κB; Radix Tetrastigmae flavonoids; TLR4