Cynandione A attenuates lipopolysaccharide-induced production of inflammatory mediators via MAPK inhibition and NF-κB inactivation in RAW264.7 macrophages and protects mice against endotoxin shock.

Abstract

Cynanchum wilfordii has been traditionally used in eastern Asia for the treatment of various diseases such as gastrointestinal diseases and arteriosclerosis. Cynandione A (CA), an acetophenone, is one of major constituents from roots of C. wilfordii. In the present study, the anti-inflammatory activities of CA were investigated in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-administered C57BL/6 N mice. CA significantly decreased LPS-induced production of nitric oxide and prostaglandin E2 in a dose-dependent manner, while CA up to 200 μM did not exhibit cytotoxic activity. Our data also showed that CA significantly attenuated expression of iNOS and COX-2 in LPS-stimulated macrophages. CA inhibited phosphorylation of IκB-α and MAP kinases such as ERK and p38. Furthermore, we demonstrated that CA inhibited translocation of NF-κB to the nucleus, transcription of the NF-κB minimal promoter and NF-κB DNA binding activity. Administration of CA significantly decreased the plasma levels of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β in LPS-injected mice and improved survival of septic mice with lethal endotoxemia. These results demonstrate that CA has effective inhibitory effects on production of inflammatory mediators via suppressing activation of NF-κB and MAPK signaling pathways, suggesting that CA may be used as a potential anti-inflammatory agent for the prevention and treatment of inflammatory diseases.

• Authors: Sung Hwan Kim, Tae Hoon Lee, Sang Min Lee, Ji Hae Park, Keun Hyung Park, Mira Jung, Hana Jung, Mohamed Antar Aziz Mohamed, Nam-In Baek, In Sik Chung, Jiyoung Kim
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 240 Issue 7 Pg. 946-54 (Jul 2015) ISSN: 1535-3699 [Electronic] England
• PMID: 25361770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by the Society for Experimental Biology and Medicine.

Chemical References

• Anti-Inflammatory Agents
• Biphenyl Compounds
• Inflammation Mediators
• Lipopolysaccharides
• NF-kappa B
• Plant Extracts
• cynandione A
• Mitogen-Activated Protein Kinase Kinases

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Biphenyl Compounds (pharmacology)
• Blotting, Western
• Electrophoretic Mobility Shift Assay
• Enzyme-Linked Immunosorbent Assay
• Inflammation Mediators (immunology, metabolism)
• Lipopolysaccharides (toxicity)
• Macrophages (drug effects, immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinase Kinases (drug effects, immunology, metabolism)
• NF-kappa B (drug effects, immunology, metabolism)
• Plant Extracts (pharmacology)
• Plant Roots
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Shock, Septic (immunology, metabolism)