3,4,5-Trihydroxycinnamic Acid Inhibits Lipopolysaccharide-Induced Inflammatory Response through the Activation of Nrf2 Pathway in BV2 Microglial Cells.
- Author:
Jae Won LEE
1
;
Yong Jun CHOI
;
Jun Ho PARK
;
Jae Young SIM
;
Yong Soo KWON
;
Hee Jae LEE
;
Sung Soo KIM
;
Wanjoo CHUN
Author Information
1. Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Republic of Korea. wchun@kangwon.ac.kr
- Publication Type:Original Article
- Keywords:
Neuro-inflammation;
3,4,5-trihydroxycinnamic acid;
Nrf2;
Heme oxygenase-1
- MeSH:
Coumaric Acids;
Heme Oxygenase-1;
Microglia;
p38 Mitogen-Activated Protein Kinases;
Phosphorylation;
Phosphotransferases;
Tetrahydrocannabinol;
Transcription Factors;
Tumor Necrosis Factor-alpha
- From:Biomolecules & Therapeutics
2013;21(1):60-65
- CountryRepublic of Korea
- Language:English
-
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.
