Cordyceps sinensis extract suppresses hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells.
OBJECTIVE
To investigate the effects of a Chinese herb Cordyceps sinensis (C. sinensis) extract on hypoxia-induced proliferation and the underlying mechanisms involved.


METHODS
This prospective study was carried out at the Central Laboratory of Yichang Central People's Hospital, Yichang, China from March 2008 to April 2010. The C. sinensis was extracted from the Chinese herb C. sinensis using aqueous alcohol extraction techniques. Forty healthy adult male Sprague Dawley rats were used in the study. The proliferation of pulmonary artery smooth muscle cells (PASMCs) was measured using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell viability was determined by trypan blue exclusion. Cell cycles were analyzed using FACSort flow cytometric analysis. The expression of proliferating cell nuclear antigen (PCNA), c-jun, and c-fos in rat PASMCs was determined by immunohistochemistry.


RESULTS
We found an increased proliferation of PASMCs and increased expression of transcription factors, c-jun and c-fos in PASMCs cultured under hypoxic conditions. The C. sinensis extract significantly inhibited hypoxia-induced cell proliferation in a dose-dependent manner. In addition, C. sinensis extract also significantly inhibited the expression of PCNA, c-jun, and c-fos in these PASMCs.


CONCLUSIONS
Our results indicated that C. sinensis extract inhibits hypoxia-induced proliferation of rat PASMCs, probably by suppressing the expression of PCNA, c-fos, c-jun, and decreasing the percentage of cells in synthesis phase, second gap phase, and mitotic phase in cell cycle (S+G2/M) phase. Our results therefore, provided novel evidence that C. sinensis extract may be used as a therapeutic reagent in the treatment of hypoxic pulmonary hypertension.
Gao
Bao-an
BA
Department of Respiratory Medicine, The First College of Clinical Medical Science of China Three Gorges University and Yichang Central People's Hospital, Yichang, China.
Yang
Jun
J
Huang
Ji
J
Cui
Xiang-jun
XJ
Chen
Shi-xiong
SX
Den
Hong-yan
HY
Xiang
Guang-ming
GM
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D032661:Cordyceps; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005434:Flow Cytometry; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011651:Pulmonary Artery; D051381:Rats; D017207:Rats, Sprague-Dawley
D004365:Drugs, Chinese Herbal; D018809:Proliferating Cell Nuclear Antigen; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun