Myricetin inhibits TNF-α-induced inflammation in A549 cells via the SIRT1/NF-κB pathway

Background: Although myricetin exerts anti-inflammation, anti-cancer, and anti-oxidation effects, the relationship between myricetin and tumor necrosis factor alpha (TNF-alpha)-stimulated inflammation in A549 cells remains unclear. This study sought to assess whether myricetin has an anti-inflammatory effect on TNF-alpha-induced A549 cells and clarify the potential mechanisms. Methods: Cell viability was examined with a Cell Counting Kit-8, and cytokine levels were determined by enzymelinked immunosorbent assay and reverse transcription-quantitative PCR. Potential mechanisms were further explored by western blotting, immunofluorescence, and SIRT1 activity assays. Results: In A549 cells, TNF-alpha stimulation upregulated the production of interleukin-6 (IL-6) and interleukin-8 (IL8). Moreover, TNF-alpha activated the nuclear factor-kappa B (NF-kappa B) pathway, as confirmed by I kappa B-alpha degradation, and phosphorylation and nuclear migration of NF-kappa B p65. However, pretreatment with myricetin significantly attenuated the observed responses triggered by TNF-alpha. Mechanistically, myricetin strongly increased the deacetylase activity through decreasing phosphorylation, but not expression, of sirtuin-1 (SIRT1) in TNF alpha-stimulated A549 cells. Myricetin-mediated SIRT1 activation was further evidenced by the decreased acetylation of NF-kappa B p65 and p53. Subsequently, all of these concurrent changes were reversed by the addition of salermide (SIRT1 inhibitor), illustrating the critical role of SIRT1 in mediation of anti-inflammatory processes by myricetin. Conclusions: Myricetin, an enhancer of SIRT1, inhibited TNF-alpha-induced NF-kappa B activation in A549 cells, therefore, reducing their inflammatory response. Our findings provide insight for novel therapies for inflammation-related diseases, such as asthma and chronic obstructive pulmonary disease.