Chrysophanol demonstrates anti-inflammatory properties in LPS-primed RAW 264.7 macrophages through activating PPAR-γ.

Abstract

Sepsis is a life-threatening disease. Inflammation is a major concomitant symptom of sepsis Chrysophanol, an anthraquinone derivative isolated from the rhizomes of rheumpalmatum, has been reported to have a protective effect against lipopolysaccharide(LPS)-induced inflammation. However, the underlying molecular mechanisms are not well understood. The aim of this study was to explore the effect and mechanism of chrysophanol on lipopolysaccharide (LPS)-induced anti-inflammatory effect of RAW264.7 cells and its involved potential mechanism. The mRNA and protein expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB) and PPAR-γ were measured by qRT-PCR and western blotting, the production of TNF-α, IL-1β was evaluated by ELISA. Then, the phosphorylation of NF-κB p65 was also detected by western blotting. And NF-κB p65 promoter activity was analyzed by the Dual-Luciferase reporter assay system as well. Meanwhile, PPAR-γ inhibitor GW9662 was performed to knockdown PPAR-γ expression in cells. Our data revealed that LPS induced the up-regulation of TNF-α, IL-1β, iNOS and NF-κB p65, the down-regulation of PPAR-γ were substantially suppressed by chrysophanol in RAW264.7 cells. Furthermore, our data also figured out that these effects of chrysophanol were largely abrogated by PPAR-γ inhibitor GW9662. Taken together, our results indicated that LPS-induced inflammation was potently compromised by chrysophanol very likely through the PPAR-γ-dependent inactivation of NF-κB in RAW264.7 cells.

• Authors: Quan Wen, Liyan Mei, Sen Ye, Xia Liu, Qin Xu, Jifei Miao, Shaohui Du, Dongfeng Chen, Chun Li, Hui Li
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 56 Pg. 90-97 (Mar 2018) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 29367091 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• 2-chloro-5-nitrobenzanilide
• Anilides
• Anthraquinones
• Anti-Inflammatory Agents
• Interleukin-1beta
• Lipopolysaccharides
• NF-kappa B
• PPAR gamma
• Tumor Necrosis Factor-alpha
• Nitric Oxide Synthase Type II
• chrysophanic acid

Topics

• Anilides (pharmacology)
• Animals
• Anthraquinones (pharmacology)
• Anti-Inflammatory Agents (pharmacology)
• Interleukin-1beta (genetics, metabolism)
• Lipopolysaccharides (immunology)
• Macrophages (drug effects, immunology)
• Mice
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• PPAR gamma (metabolism)
• RAW 264.7 Cells
• Rheum (immunology)
• Rhizome
• Sepsis (drug therapy)
• Signal Transduction
• Tumor Necrosis Factor-alpha (genetics, metabolism)