Protective roles of Cordyceps on lung fibrosis in cellular and rat models.
BACKGROUND
Cordyceps sinensis is a fungus used in traditional Chinese medicine as a tonic to soothe the lung for the treatment of fatigue and respiratory diseases. Idiopathic pulmonary fibrosis is a chronic, irreversible and debilitating lung disease showing fibroblast/myofibroblast expansion and excessive deposition of extracellular matrix in the interstitium leading to breathing difficulty. Our previous observation revealed a partial relief of lung fibrosis in patients suffering from severe acute respiratory syndrome (SARS). We hypothesize that Cordyceps has beneficial effects on lung fibrosis and the objective of this study is to explore the target(s) of Cordyceps in the relief of lung fibrosis in animal and cell models and to gain insight into its underlying mechanisms.


METHODS
A rat model of bleomycin (BLM)-induced lung fibrosis and a fibrotic cell model with transforming growth factor beta-1 induction were employed in the studies.


RESULTS
Reduction of infiltration of inflammatory cells, deposition of fibroblastic loci and collagen, formation of reactive oxygen species, and production of cytokines, as well as recovery from imbalance of MMP-9/TIMP-1, were observed in fibrotic rats after treatment with Cordyceps in preventive (from the day of BLM administration) and therapeutic (from 14 days after BLM) regimens. In a fibrotic cell model with transforming growth factor beta-1 induction, the human lung epithelial A549 acquired a mesenchymal phenotype and an increase of vimentin expression with a concomitant decrease of E-cadherin. This epithelial-mesenchymal transition could be partially reverted by cordycepin, a major component of Cordyceps.


CONCLUSIONS
The findings provide an insight into the preventive and therapeutic potentials of Cordyceps for the treatment of lung fibrosis.
School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Mengli
M
Chen
Florence W K
FW
Cheung
Ming Hung
MH
Chan
Pak Kwan
PK
Hui
Siu-Po
SP
Ip
Yick Hin
YH
Ling
Chun-Tao
CT
Che
Wing Keung
WK
Liu
D000818:Animals; D001761:Bleomycin; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D032661:Cordyceps; D003839:Deoxyadenosines / Q000494:pharmacology; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D020011:Protective Agents / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
D015820:Cadherins; D003839:Deoxyadenosines; D020011:Protective Agents; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D001761:Bleomycin; D003094:Collagen; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; C058120:cordycepin