Inhibitory effect of emodin on bleomycin-induced pulmonary fibrosis in mice.
1. Currently, there is no satisfactory treatment for pulmonary fibrosis. Emodin, a component in Chinese herbs, has been shown to have an antifibrotic effect on pancreatic fibrosis and liver fibrosis. In the present study, we tested the hypothesis that emodin may attenuate the development of pulmonary fibrosis. 2. Mice were randomly divided into five groups (n = 16 in each). One group was a control group; the remaining four groups were treated with intratracheal instillation of 3 mg/kg bleomycin (BLM). The following day, emodin (5, 10 or 20 mg/kg per day, p.o.) treatment was started for three of the BLM-treated groups and was continued for 21 days. The fourth BLM-treated group (and the control group) received daily 0.5% sodium carboxymethyl cellulose (placebo) by gavage over the same period. 3. Bleomycin challenge provoked severe pulmonary fibrosis, with marked increases in fibrosis fraction, hydroxyproline content and myeloperoxidase activity in lung tissue. Emodin treatment (10 and 20 mg/kg per day, p.o.) attenuated all these biochemical indices, as well as histopathological alterations induced by BLM. Furthermore, in mice injected with BLM, elevated levels of transforming growth factor-beta1, interleukin (IL)-4 and IL-13 were found in bronchoalveolar lavage fluid. These increases were significantly inhibited by 10 and 20 mg/kg per day emodin. 4. In cell culture, exposure of cells to 6.25, 12.5, 25 or 50 micromol/L emodin for 24 h decreased fibroblast proliferation. Treatment of cells with the same concentrations of emodin for 72 h decreased collagen production by fibroblasts. In addition, emodin (6.25, 12.5, 25 or 50 micromol/L) inhibited the steady state expression of alpha1 (I) procollagen and alpha2 (I) procollagen mRNA in a dose-dependent manner. 5. The results of the present study suggest that emodin may be effective in the treatment of pulmonary fibrosis.
Chen
Xiao-Hong
XH
Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China.
Sun
Ren-Shan
RS
Hu
Jian-Ming
JM
Mo
Zi-Yao
ZY
Yang
Zi-Feng
ZF
Jin
Guang-Yao
GY
Guan
Wen-Da
WD
Zhong
Nan-Shan
NS
D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004642:Emodin / Q000494:pharmacology / Q000627:therapeutic use*; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D001761:Bleomycin; D003094:Collagen; D009195:Peroxidase; D004642:Emodin