Macrophage Inflammation Alleviation by 20(S)-Protopanaxatriol by Inhibiting NLRP3 Inflammasome Activation
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Abstract:
The effects of 20(S)-protopanaxatriol (PPT) on NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome activation induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) were investigated to examine the role of PPT in alleviating macrophage inflammation. RAW264.7 cells were divided into a control group, an LPS group, an LPS+ATP group, and three PPT treatment groups (20, 40, and 80 μmol/L). The mRNA expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and NLRP3 were significantly increased after LPS+ATP treatment. PPT treatment markedly downregulated the mRNA levels of iNOS, IL-1β, and NLRP3; however, there were no significant changes in those of COX-2 and TNF-α. Additionally, the expression levels of NLRP3, IL-1β, and cysteinyl aspartate-specific proteinase-1 in the cell lysate of the PPT treatment group were lower than those in the LPS+ATP group; however, PPT had no effect on the translocation of nuclear factor kappa-B. Enzyme-linked immunosorbent assay revealed that PPT significantly reduced IL-1β expression levels without affecting TNF-α levels. Scanning electron microscopy observation showed that PPT notably improved the inflammatory state of RAW264.7 cells. Specifically, there was a decrease in pseudopodia formation, whereas cell folds were smoothed resulting in rounded cells. This study demonstrated that PPT exhibits immunomodulatory and anti-inflammatory effects. PPT can regulate inflammation in macrophages by inhibiting NLRP3 inflammasome activation and subsequently reducing the expression level of IL-1β. This study provides a theoretical basis for exploring the mechanism by which PPT targets the NLRP3 inflammasome and its potential impact on related drug development.
