title: Total glycosides of Yupingfeng protects against bleomycin-induced pulmonary fibrosis in rats associated with reduced high mobility group box 1 activation and epithelial-mesenchymal transition.
abstract: BACKGROUND
  Pulmonary fibrosis (PF) is a fatal inflammatory disease with limited effective strategies. Epithelial-mesenchymal transition (EMT) is a pivotal origin of myofibroblasts that secrete extracellular matrix (ECM) in the development of PF. High mobility group box 1 (HMGB1), one of the mediators of inflammation, has been proved abnormal activation in the pathogenesis of PF.
  
  
  OBJECTIVE
  The present study was aimed to investigate the potential effects of total glycoside of Yupingfeng (YPF-G), the natural compound extracted from Yupingfeng san, on HMGB1 activation and EMT in bleomycin-induced PF, which was a serious disease of respiratory system.
  
  
  METHODS
  The Sprague-Dawley (SD) rat model of PF was duplicated by intratracheal instillation of bleomycin (5 mg kg(-1)). After that, YPF-G (5, 10 mg kg(-1)) and prednisone (5 mg kg(-1)) were separately administered intragastrically, and then the rats were killed at days 14 and 28, respectively. Hematoxylin and eosin and Masson's trichrome staining were performed to assess the histopathologic level of lung tissues, western blotting and the common kits were utilized to investigate the hallmarks molecule expression of ECM and EMT, and the level of HMGB1 in lung tissues and serum.
  
  
  RESULTS
  We found that both dose of YPF-G markedly reduced bleomycin-induced alveolitis and PF in rats. Besides, the levels of HMGB1, laminin, hyaluronic acid, and hydroxyproline were effectively reduced. Meanwhile, the increased protein expression of HMGB1 and the mesenchymal markers including vimentin and alpha-smooth muscle actin, and the decreased protein expression of epithelial marker E-cadherin were dramatically inhibited after YPF-G treatment.
  
  
  CONCLUSIONS
  Our results demonstrated that YPF-G could ameliorate bleomycin-induced PF by reducing HMGB1 activation and reversing EMT.
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.|The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, China.
authors.forename: Liucheng
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui University of Chinese Medicine, 103 Meishan Road, Hefei, 230038, Anhui, China.
authors.forename: Delin
authors.initials: D
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.|The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Mo
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.|The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zhou
authors.affiliation: The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Anhui University of Chinese Medicine, 103 Meishan Road, Hefei, 230038, Anhui, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Anhui University of Chinese Medicine, 103 Meishan Road, Hefei, 230038, Anhui, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Jiangsu, 210009, Nanjing, China.
authors.forename: Lianwen
authors.initials: L
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Jiangsu, 210009, Nanjing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China. gaojianayfy@163.com.|The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China. gaojianayfy@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001761:Bleomycin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects; D006027:Glycosides; D024243:HMGB1 Protein / Q000187:drug effects*; D006909:Hydroxyproline / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D011241:Prednisone / Q000494:pharmacology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D006027:Glycosides; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D010936:Plant Extracts; C532967:yupingfeng; D001761:Bleomycin; D006909:Hydroxyproline; D011241:Prednisone
keywords: Epithelial–mesenchymal transition; High mobility group box 1; Pulmonary fibrosis; Total glycosides of Yupingfeng