Ilex kaushue and Its Bioactive Component 3,5-Dicaffeoylquinic Acid Protected Mice from Lipopolysaccharide-Induced Acute Lung Injury

被引:27
作者
Chen, Yu-Li [1 ]
Hwang, Tsong-Long [1 ,2 ,3 ,4 ,5 ,6 ]
Yu, Huang-Ping [6 ,7 ]
Fang, Jia-You [1 ,2 ,3 ,4 ,5 ,6 ]
Chong, Kowit Yu [1 ,8 ,9 ]
Chang, Yao-Wen [1 ,2 ]
Chen, Chun-Yu [6 ]
Yang, Hsuan-Wu [2 ]
Chang, Wen-Yi [2 ]
Hsieh, Pei-Wen [1 ,2 ,4 ,5 ,6 ]
机构
[1] Chang Gung Univ, Coll Med, Grad Inst Biomed Sci, Taoyuan, Taiwan
[2] Chang Gung Univ, Coll Med, Grad Inst Nat Prod, Taoyuan, Taiwan
[3] Chang Gung Univ, Hlth Aging Res Ctr, Chinese Herbal Med Res Team, Taoyuan, Taiwan
[4] Chang Gung Univ, Chang Gung Univ Sci & Technol, Res Ctr Ind Human Ecol, Taoyuan, Taiwan
[5] Chang Gung Univ, Chang Gung Univ Sci & Technol, Res Ctr Chinese Herbal Med, Taoyuan, Taiwan
[6] Chang Gung Mem Hosp, Dept Anesthesiol, Taoyuan, Taiwan
[7] Chang Gung Univ, Coll Med, Sch Med, Taoyuan, Taiwan
[8] Chang Gung Univ, Coll Med, Dept Med Biotechnol & Lab Sci, Taoyuan, Taiwan
[9] Chang Gung Mem Hosp Linkou, Dept Thorac Med, Taoyuan, Taiwan
关键词
KUDINGCHA CJ TSENG; ELASTASE INHIBITOR SIVELESTAT; FAMILY KINASES HCK; NF-KAPPA-B; NEUTROPHIL ELASTASE; METHANOL EXTRACT; CHLOROGENIC ACID; RAT PLASMA; IN-VITRO; CONSTITUENTS;
D O I
10.1038/srep34243
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Acute lung injury (ALI) is a severe respiratory disease with high mortality rates worldwide. Recent reports suggest that human neutrophil elastase (HNE) plays a key role in the inflammatory response that is characteristic of ALI, which indicates that the development of HNE inhibitors could be an efficient treatment strategy. In the current study, an enzyme-based screening assay was used to identify effective HNE inhibitors from a number of traditional Chinese medicines (TCMs). Among them, a water extract of Ilex kaushue (IKWE) effectively inhibited HNE activity (IC50, 11.37 +/- 1.59 mu g/mL). Using bioactivity-guided fractionation, one new compound and 23 known compounds were identified. Compound 6 (identified as 3,5-dicaffeoylquinic acid; 3,5-DCQA) exerted the most potent and selective inhibitory effect on HNE activity (IC50, 1.86 +/- 0.06 mu M). In a cell-based assay, 3,5-DCQA not only directly reduced superoxide generation and elastase activity but also attenuated the Src family kinase (SRKs)/Vav signaling pathway in N-formyl-L-Met-L-Leu-L-Phe (fMLF)-stimulated human neutrophils. In an animal disease model, both 3,5-DCQA and standardized IKWE protected against lipopolysacchar-ideinduced ALI in mice, which provides support for their potential as candidates in the development of new therapeutic agents for neutrophilic inflammatory diseases.
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页数:12
相关论文
共 60 条
[1]
Clinical utility of the neutrophil elastase inhibitor sivelestat for the treatment of acute respiratory distress syndrome [J].
Aikawa, Naoki ;
Kawasaki, Yasushi .
THERAPEUTICS AND CLINICAL RISK MANAGEMENT, 2014, 10 :621-629
[2]
Baset P, 1996, BIOL PHARM BULL, V19, P1479, DOI 10.1248/bpb.19.1479
[3]
Neutrophil Elastase Modulates Cytokine Expression CONTRIBUTION TO HOST DEFENSE AGAINST PSEUDOMONAS AERUGINOSA-INDUCED PNEUMONIA [J].
Benabid, Rym ;
Wartelle, Julien ;
Malleret, Laurette ;
Guyot, Nicolas ;
Gangloff, Sophie ;
Lebargy, Francois ;
Belaaouaj, Azzaq .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (42) :34883-34894
[4]
Bors W, 2004, BIOL RES, V37, P301
[5]
Design, synthesis and antithrombotic evaluation of novel dabigatran etexilate analogs, a new series of non-peptides thrombin inhibitors [J].
Chen, Dongxing ;
Wang, Shaochi ;
Diao, Xiaojuan ;
Zhu, Qihua ;
Shen, Huiliang ;
Han, Xueqing ;
Wang, Yiwei ;
Gong, Guoqing ;
Xu, Yungen .
BIOORGANIC & MEDICINAL CHEMISTRY, 2015, 23 (23) :7405-7416
[6]
The anti-inflammatory activities of Ainsliaea fragrans Champ. extract and its components in lipopolysaccharide-stimulated RAW264.7 macrophages through inhibition of NF-κB pathway [J].
Chen, Xin ;
Miao, Jingshan ;
Wang, Hao ;
Zhao, Fang ;
Hu, Jie ;
Gao, Peng ;
Wang, Yue ;
Zhang, Luyong ;
Yan, Ming .
JOURNAL OF ETHNOPHARMACOLOGY, 2015, 170 :72-80
[7]
The Src family kinases Hck and Fgr regulate neutrophil responses to N-formyl-methionyl-leucyl-phenylalanine [J].
Fumagalli, Laura ;
Zhang, Hong ;
Baruzzi, Anna ;
Lowell, Clifford A. ;
Berton, Giorgio .
JOURNAL OF IMMUNOLOGY, 2007, 178 (06) :3874-3885
[8]
Effects of caffeoyl conjugates of isoprenyl-hydroquinone glucoside and quinic acid on leukocyte function [J].
Göngora, L ;
Giner, RM ;
Máñez, S ;
Recio, MD ;
Schinella, G ;
Ríos, JL .
LIFE SCIENCES, 2002, 71 (25) :2995-3004
[9]
A systematic study on the influence of the main ingredients of an ivy leaves dry extract on the β2-adrenergic responsiveness of human airway smooth muscle cells [J].
Greunke, Christian ;
Hage-Huelsmann, Anne ;
Sorkalla, Thomas ;
Keksel, Nelli ;
Haeberlein, Felix ;
Haeberlein, Hanns .
PULMONARY PHARMACOLOGY & THERAPEUTICS, 2015, 31 :92-98
[10]
Contribution of Neutrophils to Acute Lung Injury [J].
Grommes, Jochen ;
Soehnlein, Oliver .
MOLECULAR MEDICINE, 2011, 17 (3-4) :293-307