Abstract
Curcumin is the main curcuminoid present in Curcuma longa and it has been previously reported to exhibit a wide range of pharmacological activities. In the present study, the inhibitory effects of curcumin on the inflammatory mediators released by Pam3CSK4-stimulated BV-2 microglial cells were investigated. The production of pro-inflammatory mediators and cytokines, including tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2), were measured by enzyme‑linked immunosorbent assay (ELISA). The expression of inflammatory genes, including inducible nitric oxide synthase and cyclooxygenase-2, were further investigated using reverse transcription-quantitative polymerase chain reaction. The effects of curcumin on heme oxygenase-1 (HO-1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways were analyzed by western blotting. The results revealed that curcumin dose-dependently inhibited Pam3CSK4-induced nitric oxide, PGE2, and TNF-α secretion. Curcumin suppressed the secretion of inflammatory mediators through an increase in the expression of HO-1. Curcumin induced HO-1 transcription and translation through the Nrf2/antioxidant response element signaling pathway. Inhibitory experiments revealed that HO-1 was required for the anti-inflammatory effects of curcumin. Further mechanistic studies demonstrated that curcumin inhibited neuroinflammation by suppressing NF-κB and MAPK signaling pathways in Pam3CSK4-activated microglial cells. The results of the present study suggest that curcumin may be a novel treatment for neuroinflammation-mediated neurodegenerative disorders.