Neochlorogenic acid inhibits against LPS-activated inflammatory responses through up-regulation of Nrf2/HO-1 and involving AMPK pathway.

Abstract

Acute and chronic inflammatory diseases are associated with excessive inflammation due to the accumulation of pro-inflammatory mediators and cytokines produced by macrophages. In the present study, we investigated the anti-inflammatory properties of neochlorogenic acid (nCGA) from Lonicera japonica on lipopolysaccharide (LPS)-activated inflammation in macrophages and participation of the AMPK/Nrf2 pathway. nCGA pretreatment significantly reduced the production of nitric oxide, prostaglandin E2, TNF-α, reactive oxygen species, IL-1β, and IL-6 by LPS-activated macrophages. Moreover, both transcript and protein levels of inducible nitric oxide synthase and cyclooxygenase-2 were reduced by nCGA in LPS-activated macrophages. nCGA inhibited NF-κB activation by attenuating IKKα/β and IκBα phosphorylation in LPS-stimulated macrophages. Moreover, nCGA attenuated LPS-elevated JAK-1, STAT-1, and MAPK phosphorylation. We further evaluated the possible role of nCGA in the induction of AMPK/Nrf2 signal pathways required for the protein expression of HO-1 and NQO-1. nCGA induced AMPK activation via phosphorylation of LKB1 and CaMKII and by the inhibitory phosphorylation of GSK3β. It stimulated the overexpression of Nrf2/ARE-regulated downstream proteins, such as NQO-1 and HO-1. Furthermore, the anti-inflammatory effects of nCGA were attenuated in macrophages subjected to siRNAs specific for HO-1, NQO-1, Nrf2, and AMPK. Accordingly, these results indicate that nCGA, as an AMPK/Nrf2 signal activator, prevents excessive macrophage-mediated responses associated with acute and chronic inflammatory disorders.

• Authors: Sun Young Park, Mei Ling Jin, Eun Hye Yi, Yoon Kim, Geuntae Park
• Journal: Environmental toxicology and pharmacology (Environ Toxicol Pharmacol) Vol. 62 Pg. 1-10 (Sep 2018) ISSN: 1872-7077 [Electronic] Netherlands
• PMID: 29908432 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Lipopolysaccharides
• Membrane Proteins
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Quinic Acid
• Chlorogenic Acid
• Nitric Oxide
• Heme Oxygenase-1
• Hmox1 protein, mouse
• AMP-Activated Protein Kinases
• Dinoprostone
• 5'-O-caffeoylquinic acid

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Chlorogenic Acid (analogs & derivatives, pharmacology)
• Cytokines (metabolism)
• Dinoprostone (metabolism)
• Heme Oxygenase-1 (metabolism)
• Lipopolysaccharides (pharmacology)
• Macrophages, Peritoneal (drug effects, metabolism)
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• NF-E2-Related Factor 2 (metabolism)
• Nitric Oxide (metabolism)
• Quinic Acid (analogs & derivatives, pharmacology)
• RAW 264.7 Cells
• Signal Transduction (drug effects)
• Up-Regulation