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Title 

Picroside II isolated from Pseudolysimachion rotundum var. subintegrum inhibits glucocorticoid refractory serum amyloid A (SAA) expression and SAA-induced IL-33 secretion

Authors 

Kiram LeeJin ChoiBo Kyong ChoiYoung Mi GuHyung Won RyuSei-Ryang OhHyun-Jun Lee

Publisher 

MDPI

Issue Date 

2019

Citation 

Molecules

Keywords 

Picroside IIPseudolysimachion rotundum var. subintegrumserum amyloid AIL-33steroid-resistanceairway epithelial cells

Abstract 

Chronic obstructive pulmonary disease (COPD) is a major inflammatory lung disease characterized by irreversible and progressive airflow obstruction. Although corticosteroids are often used to reduce inflammation, steroid therapies are insu cient in patients with refractory COPD. Both serum amyloid A (SAA) and IL-33 have been implicated in the pathology of steroid-resistant lung inflammation. Picroside II isolated from Pseudolysimachion rotundum var. subintegrum (Plantaginaceae) is a major bioactive component of YPL-001, which has completed phase-2a clinical trials in chronic obstructive pulmonary disease patients. In this study, we investigated whether picroside II is e ective in treating steroid refractory lung inflammation via the inhibition of the SAA-IL-33 axis. Picroside II inhibited LPS-induced SAA1 expression in human monocytes, which are resistant to steroids. SAA induced the secretion of IL-33 without involving cell necrosis. Picroside II, but not dexamethasone e ectively inhibited SAA-induced IL-33 expression and secretion. The inhibitory e ect by picroside II was mediated by suppressing the mitogen-activated protein kinase (MAPK) p38, ERK1/2, and nuclear factor- B pathways. Our results suggest that picroside II negatively modulates the SAA-IL-33 axis that has been implicated in steroid-resistant lung inflammation. These findings provide valuable information for the development of picroside II as an alternative therapeutic agent against steroid refractory lung inflammation in COPD.

URI 

https://doi.org/10.3390/molecules24102020

ISSN 

1420-3049

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-07-10


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