Curcumenol isolated from Curcuma zedoaria suppresses Akt-mediated NF-κB activation and p38 MAPK signaling pathway in LPS-stimulated BV-2 microglial cells.

Abstract

Curcumenol, a sesquiterpene isolated from Curcuma zedoaria is known to possess a variety of health and medicinal values which includes neuroprotection, anti-inflammatory, anti-tumor and hepatoprotective activities. The current study aim is to investigate the modulatory effects of curcumenol towards the lipopolysaccharides (LPS)-induced inflammation in BV-2 microglia. Curcumenol markedly decreased LPS-induced production of nitric oxide (NO), pro-inflammatory cytokines [(IL-6) and (TNF-α)] and pro-inflammatory proteins expression, iNOS and COX-2. Moreover, curcumenol inhibited NF-κB activation by suppressing the nuclear translocation of the NF-κB p65 subunit and blocking IκBα phosphorylation and degradation. Furthermore, an NF-κB inhibitor, ethyl 3,4-dihydroxycinnamate also known as caffeic acid ethyl ester (CAEE), attenuated LPS-stimulated iNOS and COX-2 expression, suggesting that NF-κB inhibition is a regulator in the expression of iNOS and COX-2 proteins. Further mechanistic study with an Akt inhibitor, triciribine hydrate (API-2), revealed that curcumenol acted through Akt-dependent NF-κB activation. Moreover, curcumenol inhibition on LPS-induced phosphorylation of p38 MAPK is confirmed by its inhibitor (SB 202190). These results indicate that curcumenol diminishes the proinflammatory mediators and the expression of the regulatory genes in LPS-stimulated BV-2 by inhibiting Akt-dependent NF-κB activation and downregulation of Akt and p38 MAPKs signaling.

• Authors: Jia Ye Lo, Muhamad Noor Alfarizal Kamarudin, Omer Abdalla Ahmed Hamdi, Khalijah Awang, Habsah Abdul Kadir
• Journal: Food & function (Food Funct) Vol. 6 Issue 11 Pg. 3550-9 (Nov 2015) ISSN: 2042-650X [Electronic] England
• PMID: 26301513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Lipopolysaccharides
• NF-kappa B
• Sesquiterpenes
• curcumenol
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Curcuma (chemistry)
• Cytokines (metabolism)
• Down-Regulation (drug effects)
• Inflammation (chemically induced, drug therapy)
• Lipopolysaccharides
• MAP Kinase Signaling System (drug effects)
• Mice
• Microglia (drug effects, metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Phosphorylation (drug effects)
• Phytotherapy
• Proto-Oncogene Proteins c-akt (metabolism)
• Sesquiterpenes (isolation & purification, pharmacology)
• Signal Transduction (drug effects)