title: 3,4,5-Trihydroxycinnamic Acid Inhibits Lipopolysaccharide-Induced Inflammatory Response through the Activation of Nrf2 Pathway in BV2 Microglial Cells.
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-α, and IL-1β. 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.
authors.affiliation: Department of Pharmacology, College of Medicine, Republic of Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Choi
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Sim
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Kwon
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Wanjoo
authors.initials: W
authors.lastname: Chun
keywords: 3; 4; 5-trihydroxycinnamic acid; Heme oxygenase-1; Neuro-inflammation; Nrf2