Ferulic acid exhibits anti-inflammatory effects by inducing autophagy and blocking NLRP3 inflammasome activation.

Abstract

BackgroundInflammation is involved in the healing process; however, when inflammation is overactivated, multiple diseases can occur. The continued discovery of new anti-inflammatory drugs is crucial in the treatment of inflammation-linked diseases.ObjectivesFerulic acid (FA), a precursor necessary for lignan synthesis, is widely distributed in plant-based whole foods and is a strong antioxidant. However, the effect of FA on the expression level of inflammatory factors in macrophages has not been fully clarified. The current study aimed to explore the anti-inflammatory effect and mechanism of ferulic acid.ResultsThe results showed that THP-1 cells were induced to differentiate into macrophages by Phorbol-12-myristate-13-acetate (PMA), and THP-1-derived macrophages were stimulated by LPS to establish an inflammatory cell model. Compared with the control group, low (5 μmol·mL−1), medium (10 μmol·mL−1), and high (20 μmol·mL−1) concentration ferulic acid groups have decreased cell viability and increased apoptosis rate in a dose-dependent manner. FA reduced the transcriptional levels of Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). Importantly, FA-induced autophagy and inhibited NLRP3 inflammasome activation. 3-MA (a widely used autophagy inhibitor) enhanced the secretion of TNF-α, IL-6 and IL-1β. Moreover, autophagy inhibition by 3-MA resulted in increased proteins expression associated with NLRP3 inflammasome signaling pathway. Besides, the inhibition of inflammasome activation by MCC950 reduced the expression of TNF-α, IL-6 and IL-1β.ConclusionIt is concluded that FA enhanced autophagy, inhibited the activation of NLRP3 inflammasome and reduced the expression and release of inflammatory factors.