Preventive effects of cristacarpin on experimentally induced uveitis by targeting NF-κB.

Abstract

Cristacarpin is a novel prenylated pterocarpan that reportedly exhibits broad anti-cancer activity by enhancing endoplasmic reticulum stress. However, whether and how cristacarpin affects in-flammatory processes remain largely unknown. In the present study, the anti-inflammatory effect of cristacarpin on lipopolysaccharide (LPS)-induced inflammation was investigated using zebrafish embryos, RAW 264.7 macrophages, and mouse uveitis models. In the non-toxic concentration range (from 20 to 100 μM), cristacarpin suppressed pro-inflammatory mediators such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, while stimulating anti-inflammatory mediators such as IL-4 and IL-10 in LPS-stimulated RAW 264.7 cells and uveitis mouse models. Cristacarpin decreased cell adhesion of macrophages through downregulation of the expression of Ninjurin1 and matrix metalloproteinases. Furthermore, cristacarpin reduced macrophage migration in zebrafish embryos in vivo. Cristacarpin also increased cytosolic levels of inhibitor of nuclear factor-κB and suppressed the nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells. Collectively, our results suggest that cristacarpin is a potential therapeutic candidate for developing ocular anti-inflammatory drugs.

• Authors: Su Jung Hwang, Won Keun Oh, Ho-Young Lee, Hyo-Jong Lee
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 145 Pg. 112474 (Jan 2022) ISSN: 1950-6007 [Electronic] France
• PMID: 34864308 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cell Adhesion Molecules, Neuronal
• Inflammation Mediators
• Interleukins
• NF-kappa B
• Nerve Growth Factors
• Ninj1 protein, mouse
• Plant Extracts
• Pterocarpans
• Tumor Necrosis Factor-alpha
• Zebrafish Proteins
• NF-KappaB Inhibitor alpha
• cristacarpin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cell Adhesion Molecules, Neuronal (metabolism)
• Disease Models, Animal
• Inflammation Mediators (metabolism)
• Interleukins (metabolism)
• Macrophages (immunology)
• Mice
• NF-KappaB Inhibitor alpha (metabolism)
• NF-kappa B (metabolism)
• Nerve Growth Factors (metabolism)
• Plant Extracts (pharmacology)
• Pterocarpans (pharmacology)
• RAW 264.7 Cells
• Tumor Necrosis Factor-alpha (metabolism)
• Uveitis (drug therapy, metabolism)
• Zebrafish
• Zebrafish Proteins (metabolism)