1 beta-Hydroxyalantolactone from Inulae Flos alleviated the progression of pulmonary fibrosis via inhibiting JNK/FOXO1/NF-kappa B pathway

doi:10.1016/j.intimp.2021.108339

	1 beta-Hydroxyalantolactone from Inulae Flos alleviated the progression of pulmonary fibrosis via inhibiting JNK/FOXO1/NF-kappa B pathway
	Yu, Bing 2; Jin, Xiao-Qing 2; Yu, Wen-Ying 4; Dong, Ying-Ying 2; Ying, Hua-Zhong 2,4; Yu, Chen-Huan 1,3,4
刊名	INTERNATIONAL IMMUNOPHARMACOLOGY
	2021-12-01
卷号	101
关键词	Sesquiterpene lactone Flavonoid Cell apoptosis ROS JNK FOXO1
ISSN号	1567-5769
DOI	10.1016/j.intimp.2021.108339
通讯作者	Yu, Chen-Huan(yuchenhuan2002@163.com)
英文摘要	Inulae Flos was widely distributed throughout Europe, Africa, and Asia, and was commonly used as a folk medicine in clinic for treating various respiratory diseases, including cough, asthma, bronchitis, pulmonary fibrosis, and pneumonia. However, the ingredients responsible for the pharmacology effects of I. Flos and the underlying mechanisms remain unclear. In this study, the effects of 16 known sesquiterpene lactones and flavonoids from I. Flos on TGF-beta 1-induced fibroblast activation were assessed by phenotypic high-content screening. Among those sixteen compounds, 1 beta-hydroxy alantolactone (HAL), the main characteristic sesquiterpene lactone from I. Flos, exhibited remarkable inhibitory activity. The further studies showed that HAL significantly inhibited the proliferation and induced the apoptosis of human fibroblast cell lines HELF and MRC-5 in a concentrationdependent manner. It also reduced intracellular ROS production, suppressed the mRNA expressions of E-cad, TGF-beta 1, Smad3, Col I, alpha-SMA and TNF-alpha, and downregulated protein expressions of alpha-SMA and F-actin. Furthermore, HAL significantly reduced the levels of HA, LN, PC-III and IV-C in serum, TNF-alpha and IL-6 in BALF, and TGF-beta 1, HYP and Col I in lung tissues of bleomycin (BLM)-treated rats. HAL significantly downregulated the expressions of p-JNK, FOXO1, p-p65, alpha-SMA, p-smad3 and Col I but upregulated p-FOXO1, which could be reversed by JNK agonist anisomycin. These results demonstrated that HAL induced the apoptosis of lung fibroblast cells activated by TGF-beta 1 and improved BLM-induced lung fibrosis in rats via inhibiting JNK/FOXO1/ NF-kappa B pathway.
资助项目	Zhejiang Natural Science Foundation[LY19H280012] ; Zhejiang Medical Science and Technology Project[2020KY527] ; Zhejiang Medical Science and Technology Project[2021KY632]
WOS关键词	GROWTH-FACTOR-BETA ; SESQUITERPENE LACTONES ; NITRIC-OXIDE ; BRITANIN ; INACTIVATION ; PATHOGENESIS ; INFLAMMATION ; FLOWERS ; L.
WOS研究方向	Immunology ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000721035400002
资助机构	Zhejiang Natural Science Foundation ; Zhejiang Medical Science and Technology Project
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/126680]
专题	中国科学院合肥物质科学研究院
通讯作者	Yu, Chen-Huan
作者单位	1.Chinese Acad Sci, Inst Canc & Basic Med, Dongfang St 150, Hangzhou 310018, Peoples R China 2.Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou 310053, Peoples R China 3.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Hangzhou 310022, Peoples R China 4.Hangzhou Med Coll, Key Lab Expt Anim & Safety Evaluat, Hangzhou 310013, Peoples R China
推荐引用方式 GB/T 7714	Yu, Bing,Jin, Xiao-Qing,Yu, Wen-Ying,et al. 1 beta-Hydroxyalantolactone from Inulae Flos alleviated the progression of pulmonary fibrosis via inhibiting JNK/FOXO1/NF-kappa B pathway[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2021,101.
APA	Yu, Bing,Jin, Xiao-Qing,Yu, Wen-Ying,Dong, Ying-Ying,Ying, Hua-Zhong,&Yu, Chen-Huan.(2021).1 beta-Hydroxyalantolactone from Inulae Flos alleviated the progression of pulmonary fibrosis via inhibiting JNK/FOXO1/NF-kappa B pathway.INTERNATIONAL IMMUNOPHARMACOLOGY,101.
MLA	Yu, Bing,et al."1 beta-Hydroxyalantolactone from Inulae Flos alleviated the progression of pulmonary fibrosis via inhibiting JNK/FOXO1/NF-kappa B pathway".INTERNATIONAL IMMUNOPHARMACOLOGY 101(2021).