Casticin inhibits COX-2 and iNOS expression via suppression of NF-κB and MAPK signaling in lipopolysaccharide-stimulated mouse macrophages.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

The fruits of Vitex rotundifolia L. are widely used to treat inflammation of the airway in Traditional Chinese medicine. Previous studies found that casticin, isolated from Vitex rotundifolia, could induce apoptosis of tumor cells. In this study, we evaluated the anti-inflammatory effects of casticin and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated macrophages.

MATERIALS AND METHODS:

RAW264.7 cells were pretreated with various concentrations of casticin (0.3-10μM), and then treated with LPS to induce inflammation. We assayed the levels of proinflammatory cytokines and prostaglandin E2 (PGE2) using ELISA, and examined the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and heme oxygenase (HO)-1 by Western blot. We also investigated the anti-inflammatory molecular mechanism by analyzing inflammatory-associated signaling pathways, including the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways.

RESULTS:

We found casticin inhibited the levels of nitric oxide and PGE2, and decreased the production of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α). In addition, iNOS and COX-2 expression levels were suppressed and casticin increased HO-1 and Nrf2 production in a concentration-dependent manner. Furthermore, casticin significantly inhibited NF-κB subunit p65 proteins in the nucleus and decreased Akt and MAPK activation.

CONCLUSION:

These results suggest that the anti-inflammatory effect of casticin is due to inhibition of proinflammatory cytokines and mediators by blocking the NF-κB, Akt, and MAPK signaling pathways.

• Authors: Chian-Jiun Liou, Wen-Bin Len, Shu-Ju Wu, Chwan-Fwu Lin, Xin-Ling Wu, Wen-Chung Huang
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 158 Pt A Pg. 310-6 (Dec 02 2014) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 25446583 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Flavonoids
• Lipopolysaccharides
• NF-kappa B
• casticin
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Cell Line
• Cyclooxygenase 2 (metabolism)
• Flavonoids (pharmacology)
• Lipopolysaccharides (pharmacology)
• MAP Kinase Signaling System (drug effects)
• Macrophages (drug effects, enzymology, metabolism)
• Mice
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nitric Oxide Synthase Type II (antagonists & inhibitors, metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)