Min Chen1, Cuifen Chen1, Yun Gao1, Dongming Li1, Dan Huang1, Ziyu Chen1, Xuanna Zhao1, Qiu Huang1, Dong Wu1, Tianwen Lai1, Guomei Su1, Bin Wu2, Beixian Zhou3. 1. Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China. 2. Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China. Electronic address: wubin621011@126.com. 3. Department of Pharmacy, The People's Hospital of Gaozhou, Gaozhou, Guangdong, 525200, PR China. Electronic address: zbeixian@126.com.
Abstract
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 α (TNF-α)-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-α-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-α-stimulated 16-HBE cells. Bergenin blocked TNF-α-mediated activation of nuclear factor κB (NF-κB) signaling and NF-κB 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-κB-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-α-induced proinflammatory responses by augmenting SIRT1 activity to block the NF-κB signaling pathway, which may provide beneficial effects for the treatment of airway inflammation associated with asthma.
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 α (TNF-α)-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-α-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-α-stimulated 16-HBE cells. Bergenin blocked TNF-α-mediated activation of nuclear factor κB (NF-κB) signaling and NF-κB 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-κB-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-α-induced proinflammatory responses by augmenting SIRT1 activity to block the NF-κB signaling pathway, which may provide beneficial effects for the treatment of airway inflammation associated with asthma.