Rhein attenuates lipopolysaccharide-primed inflammation through NF-κB inhibition in RAW264.7 cells: targeting the PPAR-γ signal pathway.

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.

• Authors: Quan Wen, Jifei Miao, Ngaikeung Lau, Chaoying Zhang, Peng Ye, Shaohui Du, Liyan Mei, Huandi Weng, Qin Xu, Xia Liu, Dongfeng Chen, Fengxue Zhang, Chun Li, Hui Li
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 98 Issue 6 Pg. 357-365 (Jun 2020) ISSN: 1205-7541 [Electronic] Canada
• PMID: 31846359 (Publication Type: Journal Article)

Chemical References

• Anthraquinones
• Anti-Inflammatory Agents
• Lipopolysaccharides
• NF-kappa B
• PPAR gamma
• rhein

Topics

• Animals
• Anthraquinones (pharmacology, therapeutic use)
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Cell Survival (drug effects)
• Gene Expression Regulation (drug effects)
• Inflammation (drug therapy, metabolism, pathology)
• Lipopolysaccharides (pharmacology)
• Mice
• NF-kappa B (antagonists & inhibitors)
• PPAR gamma (metabolism)
• RAW 264.7 Cells
• Signal Transduction (drug effects)