Ilex kaushue and Its Bioactive Component 3,5-Dicaffeoylquinic Acid Protected Mice from Lipopolysaccharide-Induced Acute Lung Injury.
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 μg/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 μM). 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 lipopolysaccharide-induced ALI in mice, which provides support for their potential as candidates in the development of new therapeutic agents for neutrophilic inflammatory diseases.
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Yu-Li
YL
Chen
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.|Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan, Taiwan.|Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Tsong-Long
TL
Hwang
Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|School Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Huang-Ping
HP
Yu
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.|Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan, Taiwan.|Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Jia-You
JY
Fang
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Kowit Yu
KY
Chong
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Yao-Wen
YW
Chang
Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Chun-Yu
CY
Chen
Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Hsuan-Wu
HW
Yang
Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Wen-Yi
WY
Chang
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan, Taiwan.|Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Pei-Wen
PW
Hsieh
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