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. CONCLUSION: 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.

Pulmonary hypertension (PH) is characterized by elevated pulmonary artery pressure (PAP), pulmonary vascular remodeling and right ventricular hypertrophy, which are mainly due to endothelial dysfunction. Electro-acupuncture has shown beneficial effects on cardiovascular homeostasis, but little evidence has been obtained on pulmonary effects. The goal of the present study was to investigate whether electro-acupuncture on bladder-13 and -15 points can protect against chronic hypoxia-induced PH by regulating endothelium-derived endothelin (ET)-1 and endothelial nitric oxide synthase (eNOS). Male Wistar rats were exposed to hypoxia to induce PH. Hemodynamic analysis revealed that mean PAP was similar under normoxic conditions. Chronic hypoxia increased mean PAP to 37 +/- 3 mmHg, and electro-acupuncture attenuated it to 29 +/- 3 mmHg. Absolute right ventricular weight was ameliorated by electro-acupuncture from 0.288 +/- 0.048 g to 0.228 +/- 0.029 g under hypoxic conditions. Hypoxia-induced right ventricular hypertrophy index decreased from 0.477 +/- 0.069 to 0.378 +/- 0.053 with electro-acupuncture treatment. Histological examination revealed that hypoxic rats showed increased medial pulmonary artery wall thickness as well as muscularization. However, these alternations by chronic hypoxia were attenuated by electro-acupuncture. There was no difference in eNOS or ET-1 between groups under normoxic conditions. Electro-acupuncture treatment significantly improved the circulating eNOS concentration (365.36 +/- 31.51 pg/mL) compared with only hypoxia exposure (247.60 +/- 30.64 pg/mL). In lung homogenate, levels of eNOS under hypoxia increased from 684.96 +/- 117.90 to 869.86 +/- 197.61 pg/mg by electro-acupuncture treatment. Levels of ET-1 changed oppositely to eNOS in response to electro-acupuncture (ET-1 in plasma, 29.44 +/- 2.09 versus 20.70 +/- 2.37 pg/mL; ET-1 in lung homogenate, 120.51 +/- 3.03 versus 110.60 +/- 4.04 pg/mg). In conclusion, these results indicated that treatment with electro-acupuncture can protect against hypoxia-induced PH, possibly by regulating the balance of endothelium-derived vasoconstrictors and vasodilators.