Background Inflammation 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. Objectives Ferulic 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. Results The 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. Conclusion It is concluded that FA enhanced autophagy, inhibited the activation of NLRP3 inflammasome and reduced the expression and release of inflammatory factors.

Ferulic acid (FA) is a natural polyphenol, a derivative of cinnamic acid, widely found in Angelica, Chuanxiong and other fruits, vegetables and traditional Chinese medicine. FA contains methoxy, 4-hydroxy and carboxylic acid functional groups that bind covalently to neighbouring adjacent unsaturated Cationic C and play a key role in many diseases related to oxidative stress. Numerous studies have shown that ferulic acid protects liver cells and inhibits liver injury, liver fibrosis, hepatotoxicity and hepatocyte apoptosis caused by various factors. FA has protective effects on liver injury induced by acetaminophen, methotrexate, antituberculosis drugs, diosbulbin B and tripterygium wilfordii, mainly through the signal pathways related to TLR4/NF-κB and Keap1/Nrf2. FA also has protective effects on carbon tetrachloride, concanavalin A and septic liver injury. FA pretreatment can protect hepatocytes from radiation damage, protects the liver from damage caused by fluoride, cadmium and aflatoxin b1. At the same time, FA can inhibit liver fibrosis, inhibit liver steatosis and reduce lipid toxicity, improve insulin resistance in the liver and exert the effect of anti-liver cancer. In addition, signalling pathways such as Akt/FoxO1, AMPK, PPAR γ, Smad2/3 and Caspase-3 have been shown to be vital molecular targets for FA involvement in improving various liver diseases. Recent advances in the pharmacological effects of ferulic acid and its derivatives on liver diseases were reviewed. The results will provide guidance for the clinical application of ferulic acid and its derivatives in the treatment of liver diseases.