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- Title
Rhein attenuates lipopolysaccharide-primed inflammation through NF-κB inhibition in RAW264.7 cells: targeting the PPAR-γ signal pathway.
- Authors
Wen, Quan; Miao, Jifei; Lau, Ngaikeung; Zhang, Chaoying; Ye, Peng; Du, Shaohui; Mei, Liyan; Weng, Huandi; Xu, Qin; Liu, Xia; Chen, Dongfeng; Zhang, Fengxue; Li, Chun; Li, Hui
- Abstract
Inflammation is a common inducer of numerous severe diseases such as sepsis. The NF-κB signaling pathway plays a key role in the inflammatory process. Its activation promotes the release of pro-inflammatory mediators like inducible nitric oxide synthase and tumor necrosis factor alpha. Peroxisome proliferator-activated receptor gamma (PPAR-γ) inactivates nuclear factor kappa B (NF-κB) and subsequently attenuates inflammation. Rhein, an agent isolated from rhubarb, has been known to have anti-inflammatory effects. However, its influence on PPAR-γ remains largely unknown. In this study, an inflammation model was constructed by stimulating RAW264.7 cells with lipopolysaccharide. Rhein was used as a therapeutic agent, while rosiglitazone (PPAR-γ activator) and GW9662 (PPAR-γ inhibitor) were used as disrupters for in depth studies. The results demonstrated that rhein inhibits NF-κB activation and inflammatory factor release. However, GW9662 significantly reduced this effect, indicating that PPAR-γ is a critical mediator in the rhein-mediated anti-inflammatory process. Additionally, positive modulation of PPAR-γ expression and activity by rosiglitazone correspondingly influenced the effects of rhein on inflammatory factors and NF-κB expression. We also found that rhein could enhance PPAR-γ, NF-κB, and histone deacetylase 3 (HDAC3) binding. These results indicate that rhein exerts its anti-inflammation function by regulating the PPAR-γ–NF-κB–HDAC3 axis.
- Subjects
PEROXISOME proliferator-activated receptors; NUCLEAR receptors (Biochemistry); NF-kappa B; NITRIC-oxide synthases; TUMOR necrosis factors; HISTONE deacetylase
- Publication
Canadian Journal of Physiology & Pharmacology, 2020, Vol 98, Issue 6, p357
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2019-0389