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KMID : 1034820220180040509
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Molecular & Cellular Toxicology
2022 Volume.18 No. 4 p.509 ~ p.519
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Ferulic acid exhibits anti-inflammatory effects by inducing autophagy and blocking NLRP3 inflammasome activation
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Liu Yongjuan
Shi Lu
Qiu Wenhong
Shi Yingying
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Abstract
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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.
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KEYWORD
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Ferulic acid, Macrophage, Autophagy, NLRP3 inflammasome, Inflammatory factor
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