Verproside, the Most Active Ingredient in YPL-001 Isolated from Pseudolysimachion rotundum var. subintegrum, Decreases Inflammatory Response by Inhibiting PKCd Activation in Human Lung Epithelial Cells
International journal of molecular sciences(2023)
摘要
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease which causes breathing problems. YPL-001, consisting of six iridoids, has potent inhibitory efficacy against COPD. Although YPL-001 has completed clinical trial phase 2a as a natural drug for COPD treatment, the most effective iridoid in YPL-001 and its mechanism for reducing airway inflammation remain unclear. To find an iridoid most effectively reducing airway inflammation, we examined the inhibitory effects of the six iridoids in YPL-001 on TNF or PMA-stimulated inflammation (IL-6, IL-8, or MUC5AC) in NCI-H292 cells. Here, we show that verproside among the six iridoids most strongly suppresses inflammation. Both TNF/NF-?B-induced MUC5AC expression and PMA/PKCd/EGR-1-induced IL-6/-8 expression are successfully reduced by verproside. Verproside also shows anti-inflammatory effects on a broad range of airway stimulants in NCI-H292 cells. The inhibitory effect of verproside on the phosphorylation of PKC enzymes is specific to PKCd. Finally, in vivo assay using the COPD-mouse model shows that verproside effectively reduces lung inflammation by suppressing PKCd activation and mucus overproduction. Altogether, we propose YPL-001 and verproside as candidate drugs for treating inflammatory lung diseases that act by inhibiting PKCd activation and its downstream pathways.
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关键词
EGR-1,MUC5AC,NF-κB,P. rotundum var. subintegrum,chronic obstructive pulmonary disease,iridoid
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