title: Paeoniflorin, the main active constituent of Paeonia lactiflora roots, attenuates bleomycin-induced pulmonary fibrosis in mice by suppressing the synthesis of type I collagen.
abstract: BACKGROUND
  In the theory of traditional Chinese medicine, pulmonary fibrosis (PF) belongs to pulmonary arthralgia, which means blood stasis in lung tissue. The roots of Paeonia lactiflora Pall are usually used to relieve the symptoms of this disease by promoting blood circulation and removing blood stasis. Paeoniflorin, the main active ingredient of P. lactiflora, may have anti-PF potential.
  
  
  OBJECTIVE
  This study aimed to investigate the effects and underlying mechanisms of paeoniflorin on bleomycin (BLM)-induced PF in mice.
  
  
  METHODS
  The PF model was established in mice by an intratracheal instillation of BLM. Paeoniflorin (25, 50, 100mg/kg) and prednisone (6mg/kg), as a positive control, were orally administered for consecutive 21 days. Histopathological changes were evaluated by hematoxylin and eosin stain and Masson's trichrome stain. The content of hydroxyproline was detected by using kits. The contents of type I collagen, TGF-β1 and IFN-γ were detected by ELISA. The levels of α-SMA, Smad4, Smad7 and the phosphorylations of Smad2/3 were detected by western blot. The mRNA expressions of MMP-1 and TIMP-1 were detected by RT-PCR.
  
  
  RESULTS
  In mice treated with BLM, paeoniflorin (50mg/kg) significantly prolonged the survival periods, attenuated infiltration of inflammatory cells, interstitial fibrosis, and deposition of extracellular matrix in lung tissues. It also decreased the contents of hydroxyproline (a marker of collagens), type I collagen and α-SMA (an indicator of myofibroblasts) in lung tissues of mice. Paeoniflorin down-regulated the expressions of TGF-β1, Smad4 and the phosphorylations of Smad2/3, while up-regulated the expression of Smad7 in lung tissues. Moreover, paeoniflorin increased the content of IFN-γ. But, it only slightly affected mRNA expressions of MMP-1 and TIMP-1 in lung tissues of mice.
  
  
  CONCLUSIONS
  Paeoniflorin attenuates PF by suppressing type I collagen synthesis via inhibiting the activation of TGF-β/Smad pathway and increasing the expression of IFN-γ.
authors: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors: Yu
authors: Y
authors: Ji
authors: Ting
authors: T
authors: Wang
authors: Zhi-Feng
authors: ZF
authors: Wei
authors: Guo-Xun
authors: GX
authors: Lu
authors: Si-de
authors: SD
authors: Jiang
authors: Yu-Feng
authors: YF
authors: Xia
authors: Yue
authors: Y
authors: Dai
mesh_terms: D000818:Animals; D001565:Benzoates / Q000302:isolation & purification / Q000627:therapeutic use*; D001761:Bleomycin / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000302:isolation & purification / Q000627:therapeutic use*; D024042:Collagen Type I / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000627:therapeutic use*; D005960:Glucosides / Q000302:isolation & purification / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D039821:Monoterpenes; D029596:Paeonia / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006027:Glycosides
chemical_list: D001565:Benzoates; D001761:Bleomycin; D001952:Bridged-Ring Compounds; D024042:Collagen Type I; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D039821:Monoterpenes; C015423:peoniflorin; D006027:Glycosides
keywords: Extracellular matrix; Paeoniflorin; Pulmonary fibrosis; TGF-β/Smad pathway; Type I collagen