Bergenin-activated SIRT1 inhibits TNF-α-induced proinflammatory response by blocking the NF-κB signaling pathway

Background: Bergenin, a type of polyphenol compound, exhibits antiulcerogenic, anti-inflammatory, antitussive, and burn wound-healing properties. However, its therapeutic effect on tumor necrosis factor alpha (TNF-alpha)-induced proinflammatory responses in the airway and potential mechanisms of actions are still unclear. This study aimed to investigate the anti-inflammatory effects and mechanism of bergenin in TNF-alpha-stimulated human bronchial epithelial (16-HBE) cells. Methods: Cell Counting Kit-8 was used to evaluate cytotoxicity. Cytokine expression was analyzed by reverse transcription-quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay. Immunofluorescence, western blot, and sirtuin-1 (SIRT1) activity assays were employed to investigate potential molecular mechanisms. Results: Bergenin obviously decreased both mRNA and protein expression levels of interleukins 6 and 8 (IL-6 and IL-8) in TNF-alpha-stimulated 16-HBE cells. Bergenin blocked TNF-alpha-mediated activation of nuclear factor kappa B (NF-kappa B) signaling and NF-kappa B nuclear translocation. Interestingly, RT-qPCR and western blotting results revealed that bergenin did not affect SIRT1 expression, but significantly increased its activity. Bergenin-mediated SIRT1 activation was further confirmed by results indicating decreased acetylation levels of NF-kappa B-p65 and p53. Moreover, the inhibitory effects of bergenin on mRNA and protein expression levels of IL-6 and IL-8 were reversed by a SIRT1 inhibitor. In addition, combining bergenin and dexamethasone (DEX) yielded additive effects on the reduction of IL-6 and IL-8 expression. Conclusions: These findings demonstrate that bergenin could suppress TNF-alpha-induced proinflammatory responses by augmenting SIRT1 activity to block the NF-kappa B signaling pathway, which may provide beneficial effects for the treatment of airway inflammation associated with asthma.