Biomol Ther.  2013 Jan;21(1):60-65.

3,4,5-Trihydroxycinnamic Acid Inhibits Lipopolysaccharide-Induced Inflammatory Response through the Activation of Nrf2 Pathway in BV2 Microglial Cells

• Lee JW
• Choi YJ
• Park JH
• Sim JY
• Kwon YS
• Lee HJ
• Kim SS
• Chun W

Abstract

3,4,5-Trihydroxycinnamic acid (THC) is a derivative of hydroxycinnamic acids, which have been reported to possess a variety of biological properties such as anti-inflammatory, anti-tumor, and neuroprotective activities. However, biological activity of THC has not been extensively examined. Recently, we reported that THC possesses anti-inflammatory activity in LPS-stimulated BV2 microglial cells. However, its precise mechanism by which THC exerts anti-inflammatory action has not been clearly identified. Therefore, the present study was carried out to understand the anti-inflammatory mechanism of THC in BV2 microglial cells. THC effectively suppressed the LPS-induced induction of pro-inflammatory mediators such as NO, TNF-alpha, and IL-1beta. THC also suppressed expression of MCP-1, which plays a key role in the migration of activated microglia. To understand the underlying mechanism by which THC exerts these anti-inflammatory properties, involvement of Nrf2, which is a cytoprotective transcription factor, was examined. THC resulted in increased phosphorylation of Nrf2 with consequent expression of HO-1 in a concentration-dependent manner. THC-induced phosphorylation of Nrf2 was blocked with SB203580, a p38 MAPK inhibitor, indicating that p38 MAPK is the responsible kinase for the phosphorylation of Nrf2. Taken together, the present study for the first time demonstrates that THC exerts anti-inflammatory properties through the activation of Nrf2 in BV2 microglial cells, suggesting that THC might be a valuable therapeutic adjuvant for the treatment of inflammation-related disorders in the CNS.

Keyword

Neuro-inflammation; 3,4,5-trihydroxycinnamic acid; Nrf2; Heme oxygenase-1

MeSH Terms

Coumaric Acids
Heme Oxygenase-1
Microglia
p38 Mitogen-Activated Protein Kinases
Phosphorylation
Phosphotransferases
Tetrahydrocannabinol
Transcription Factors
Tumor Necrosis Factor-alpha
Coumaric Acids
Heme Oxygenase-1
Phosphotransferases
Tetrahydrocannabinol
Transcription Factors
Tumor Necrosis Factor-alpha
p38 Mitogen-Activated Protein Kinases