Paeoniflorin, the main active constituent of Paeonia lactiflora roots, attenuates bleomycin-induced pulmonary fibrosis in mice by suppressing the synthesis of type I collagen

Ethnopharmacolog-ical relevance: 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. Aim of study: This study aimed to investigate the effects and underlying mechanisms of paeoniflorin on bleomycin (BLM)-induced PF in mice. Materials and Methods: The PF model was established in mice by an intratracheal instillation of BLM. Paeoniflorin (25, 50, 100 mg/kg) and prednisone (6 mg/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-beta 1 and IFN-gamma were detected by ELISA. The levels of alpha-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 (50 mg/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 alpha-SMA (an indicator of myofibroblasts) in lung tissues of mice. Paeoniflorin down-regulated the expressions of TGF-beta 1, Smad4 and the phosphorylations of Smad2/3, while up-regulated the expression of Smad7 in lung tissues. Moreover, paeoniflorin increased the content of IFN-gamma. 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-beta/Smad pathway and increasing the expression of IFN-gamma. (C) 2013 Elsevier Ireland Ltd. All rights reserved.