Rhein attenuates lipopolysaccharide-primed inflammation through NF-κB inhibition in RAW 264.7 cells: targeting the PPARγ signal pathway.

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 iNOS and TNF-α. PPAR-γ inactivates NF-κB, and subsequently attenuates inflammation. Rhein, an agent isolated from rhubarb, has been known to have anti-inflammatory effects. However, its influence on PPARγ remains largely unknown. In this study, an inflammation model was constructed, by stimulating RAW264.7 cells with Lipopolysaccharide (LPS). Rhein was used as a therapeutic agent, while rosiglitazone (PPAR-γ activator) and GW9662 (PPAR-γ inhibitor) 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 PPARγ, NF-κB, and histone deacetylases 3 (HDAC3) binding. These results indicate that rhein exerts its anti-inflammation function by regulating the PPAR-γ-NF-κB-HDAC3 axis.