Tussilagone suppressed the production and gene expression of MUC5AC mucin via regulating nuclear factor-kappa B signaling pathway in airway epithelial cells

Abstract

In the present study, we investigated whether tussilagone, a natural product derived from Tussilago farfara, significantly affects the production and gene expression of airway MUC5AC mucin. Confluent NCI-H292 cells were pretreated with tussilagone for 30 min and then stimulated with EGF (epidermal growth factor) or PMA (phorbol 12-myristate 13-acetate) for 24 h or the indicated periods. The MUC5AC mucin gene expression was measured by RT-PCR. Production of MUC5AC mucin protein was measured by ELISA. To elucidate the action mechanism of tussilagone, effect of tussilagone on PMA-induced NF-κB signaling pathway was investigated by western blot analysis. Tussilagone significantly inhibited the production of MUC5AC mucin protein and down-regulated the expression of MUC5AC mucin gene, induced by EGF or PMA. Tussilagone inhibited PMA-induced activation (phosphorylation) of inhibitory kappa B kinase (IKK), and thus phosphorylation and degradation of inhibitory kappa Ba (IκBα). Tussilagone inhibited PMA-induced phosphorylation and nuclear translocation of nuclear factor kappa B (NF-κB) p65. This, in turn, led to the down-regulation of MUC5AC protein production in NCI-H292 cells. These results suggest that tussilagone can regulate the production and gene expression of mucin by acting on airway epithelial cells through regulation of NF-κB signaling pathway.

Tussilagone Inhibits Osteoclastogenesis and Periprosthetic Osteolysis by Suppressing the NF-κB and P38 MAPK Signaling Pathways

“…Comparatively, most previous studies have suggested that TUS suppresses the activation of NF-kB pathway, while the modulated targets vary. Cheon et al (2018), Choi et al (2018), Hwang et al (2018), Kim et al (2017b), Lee et al (2016) and Lim et al (2008) all have reported that TUS blocks NF-kB pathway in exogenous-agent-induced colitis mice, airway epithelial cells, focal cerebral ischemia rats, septic mice, skin inflammation mice, and BV-2 microglial cells by attenuating the nuclear translocation of p65 subunit and the phosphorylation and (or) degradation of IkBa. Among them, Choi et al (2018) have also observed the alleviation of phosphorylated IKK complex.…”

“…TUS, the main component of T. farfara, was described to have anti-platelet-aggregation and cardiovascular-respiratory stimulating effects in previous studies (Hwang et al, 1987;Li and Wang, 1988). In recent years, several studies have proven beneficial in the treatment of diseases such as diabetic obesity (Park et al, 2008), cancers , and various inflammatory diseases (Lee et al, 2016;Kim et al, 2017b;Cheon et al, 2018;Choi et al, 2018;Hwang et al, 2018).…”

“…Additionally, some scholars have studied the metabolic patterns and parameters of TUS and set a foundation for further systematic research in patients (Liu et al, 2008;Zhang et al, 2015;Cheng et al, 2018b). In terms of molecular mechanism, many studies have indicated that TUS suppresses exogenous-agent-stimulated inflammation by downregulating NF-kB signaling in different samples including human colonic tissues, airway epithelial cells, and dendritic and microglial cells (Park et al, 2014;Cheon et al, 2018;Choi et al, 2018;Hwang et al, 2018). Some scholars have reported that TUS may repress the MAPK signaling (including JNK, ERK, and p38 pathways) and then decrease production of inflammatory mediators in different cell lines and animal models (Kim et al, 2017b;Hwang et al, 2018).…”

“…Tussilagone (TUS) is a sesquiterpenoid isolated from the flower of Tussilago farfara or some other species in the genus Tussilago. Previous studies have suggested that this natural compound exerts therapeutic effects in inflammatory pulmonary diseases (Choi et al, 2018), inflammatory intestinal diseases (IBD) (Cheon et al, 2018), ischemic stroke (Hwang et al, 2018), colon cancer , obesity and type 2 diabetes (Park et al, 2008), demonstrating diverse effect in regulating pathophysiological changes like anti-inflammation (Hwangbo et al, 2009;Lee et al, 2016;Kim et al, 2017b), antioxidation (Park et al, 2014;Qin et al, 2014), antitumor . Especially, TUS was found to attenuate lipopolysaccharide (LPS)-induced inflammatory mediator production in RAW264.7 cells via NF-kB and (or) MAPK signaling cascades (Hwangbo et al, 2009;Lee et al, 2016;Kim et al, 2017b), therefore it may be a possible drug candidate for bone protection by suppressing osteoclast formation and activation.…”

Tussilagone Inhibits Osteoclastogenesis and Periprosthetic Osteolysis by Suppressing the NF-κb and p38 MAPK Signaling Pathways

“…Tussilagone (TUS) is a type of sesquiterpenoids that was isolated from the flower of Tussilago Farfara or some other species in the genus Tussilago. Previous studies suggested that this natural compound exerts therapeutical effects in inflammatory pulmonary diseases [16], inflammatory intestinal diseases (IBD) [17], ischemic stroke [18], colon cancer [19], obesity and type 2 diabetes [20], demonstrating multiple regulatory characteristics in diverse pathophysiological changes like antiinflammation [21][22][23], anti-oxidation [24,25], anti-tumor [19]. Especially, TUS was found attenuating lipopolysaccharide (LPS)-induced inflammatory mediators production in RAW264.7 cell via NF-κB and (or) MAPK signaling cascades in several studies [21][22][23], therefore may falling in the candidates of possible drugs to protect bone by suppressing osteoclast formation and activation.…”