Total ginsenosides suppress monocrotaline-induced pulmonary hypertension in rats: involvement of nitric oxide and mitogen-activated protein kinase pathways.
BACKGROUND
Ginsenosides have been shown to exert beneficial pharmacological effects on the central nervous, cardiovascular, and endocrine systems. We sought to determine whether total ginsenosides (TG) inhibit monocrotaline (MCT)-induced pulmonary hypertension and to elucidate the underlying mechanism.


METHODS
MCT-intoxicated rats were treated with gradient doses of TG, with or without N (G)-nitro-l-arginine methyl ester. The levels of molecules involving the regulation of nitric oxide and mitogen-activated protein kinase pathways were determined.


RESULTS
TG ameliorated MCT-induced pulmonary hypertension in a dose-dependent manner, as assessed by the right ventricular systolic pressure, the right ventricular hypertrophy index, and pulmonary arterial remodeling. Furthermore, TG increased the levels of pulmonary nitric oxide, endothelial nitric oxide synthase, and cyclic guanosine monophosphate. Lastly, TG increased mitogen-activated protein kinase phosphatase-1 expression and promoted the dephosphorylation of extracellular signal-regulated protein kinases 1/2, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase 1/2.


CONCLUSIONS
TG attenuates MCT-induced pulmonary hypertension, which may involve in part the regulation of nitric oxide and mitogen-activated protein kinase pathways.
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China; Department of Pharmacy, Luoyang Orthopedic Hospital, Orthopedics Hospital of Henan Province, Luoyang, Henan, China.
Na
N
Qin
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
Wei
W
Yang
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China; Hong Hui Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
Dongxu
D
Feng
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China; Hong Hui Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
Xinwen
X
Wang
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
Muyao
M
Qi
Department of Pharmacy, Luoyang Orthopedic Hospital, Orthopedics Hospital of Henan Province, Luoyang, Henan, China.
Tianxin
T
Du
Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
Hongzhi
H
Sun
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
Shufang
S
Wu
endothelial nitric oxide synthase; mitogen-activated protein kinases; nitric oxide; pulmonary hypertension; total ginsenoside