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.