title: Grape seed extract ameliorates bleomycin-induced mouse pulmonary fibrosis.
abstract: Pulmonary fibrosis is common in a variety of inflammatory lung diseases, such as interstitial pneumonia, chronic obstructive pulmonary disease, and silicosis. There is currently no effective clinical drug treatment. It has been reported that grape seed extracts (GSE) has extensive pharmacological effects with minimal toxicity. Although it has been found that GSE can improve the lung collagen deposition and fibrosis pathology induced by bleomycin in rat, its effects on pulmonary function, inflammation, growth factors, matrix metalloproteinases and epithelial-mesenchymal transition remain to be researched. In the present study, we studied whether GSE provided protection against bleomycin (BLM)-induced mouse pulmonary fibrosis. ICR strain mice were treated with BLM in order to establish pulmonary fibrosis models. GSE was given daily via intragastric administration for three weeks starting at one day after intratracheal instillation. GSE at 50 or 100mg/kg significantly reduced BLM-induced inflammatory cells infiltration, proinflammatory factor protein expression, and hydroxyproline in lung tissues, and improved pulmonary function in mice. Additionally, treatment with GSE also significantly impaired BLM-induced increases in lung fibrotic marker expression (collagen type I alpha 1 and fibronectin 1) and decreases in an anti-fibrotic marker (E-cadherin). Further investigation indicated that the possible molecular targets of GSE are matrix metalloproteinases-9 (MMP-9) and TGF-β1, given that treatment with GSE significantly prevented BLM-induced increases in MMP-9 and TGF-β1 expression in the lungs. Together, these results suggest that supplementation with GSE may improve the quality of life of lung fibrosis patients by inhibiting MMP-9 and TGF-β1 expression in the lungs.
authors.affiliation: Medical College of Yangzhou University, 11 Huaihai Road, Yangzhou 225001, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of Respiratory Drugs Research, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Jiang
authors.affiliation: Medical College of Yangzhou University, 11 Huaihai Road, Yangzhou 225001, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Liu
authors.affiliation: Medical College of Yangzhou University, 11 Huaihai Road, Yangzhou 225001, China.
authors.forename: Ling-Tian
authors.initials: LT
authors.lastname: Ge
authors.affiliation: Key Laboratory of Respiratory Drugs Research, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Key Laboratory of Respiratory Drugs Research, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Respiratory Drugs Research, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Yong-Liang
authors.initials: YL
authors.lastname: Jia
authors.affiliation: Key Laboratory of Respiratory Drugs Research, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Xin-Wei
authors.initials: XW
authors.lastname: Dong
authors.affiliation: Medical College of Yangzhou University, 11 Huaihai Road, Yangzhou 225001, China. Electronic address: jgz7718@sina.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Respiratory Drugs Research, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: xieqm@zju.edu.cn.
authors.forename: Qiang-Min
authors.initials: QM
authors.lastname: Xie
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D056604:Grape Seed Extract / Q000008:administration & dosage / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008813:Mice, Inbred ICR; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012129:Respiratory Function Tests; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000903:Antibiotics, Antineoplastic; D056604:Grape Seed Extract; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Anti-fibrotic effect; Anti-inflammation; Bleomycin; Grape seed extract; Lung inflammation; Pulmonary fibrosis; Pulmonary toxicology