TY  - JOUR
AU  - GAO Yan
AU  - CHU Shi-feng
AU  - LI Jian-ping
AU  - ZHANG Zhao
AU  - YAN Jia-qing
AU  - WEN Zhi-lin
AU  - XIA Cong-yuan
AU  - MOU Zheng
AU  - WANG Zhen-zhen
AU  - HE Wen-bin
AU  - GUO Xiao-feng
AU  - WEI Gui-ning
AU  - CHEN Nai-hong
PY  - 2017
TI  - Protopanaxtriol protects against 3-nitropropionic acid-induced oxidative stress in a rat model of Huntington’s disease
JF  - Acta Pharmacologica Sinica; Vol 36, No 3 (March 2015): Acta Pharmacologica Sinica
Y2  - 2017
KW  - 
N2  -  Aim:  Protopanaxtriol (Ppt) is extracted from Panax ginseng Mayer. In the present study, we investigated whether Ppt could protect against 3-nitropropionic acid (3-NP)-induced oxidative stress in a rat model of Huntington’s disease (HD) and explored the mechanisms of action.  Methods:  Male SD rats were treated with 3-NP (20 mg/kg on d 1, and 15 mg/kg on d 2–5, ip). The rats received Ppt (5, 10, and 20 mg/kg, po) daily prior to 3-NP administration. Nimodipine (12 mg/kg, po) or N-acetyl cysteine (NAC, 100 mg/kg, po) was used as positive control drugs. The body weight and behavior were monitored within 5 d. Then the animals were sacrificed, neuronal damage in striatum was estimated using Nissl staining. Hsp70 expression was detected with immunohistochemistry. Reactive oxygen species (ROS) generation was measured using dihydroethidium (DHE) staining. The levels of components in the Nrf2 pathway were measured with immunohistochemistry and Western blotting.  Results:  3-NP resulted in a marked reduction in the body weight and locomotion activity accompanied by progressive striatal dysfunction. In striatum, 3-NP caused ROS generation mainly in neurons rather than in astrocytes and induced Hsp70 expression. Administration of Ppt significantly alleviated 3-NP-induced changes of body weight and behavior, decreased ROS production and restored antioxidant enzymes activities in striatum. Moreover, Ppt directly scavenged free radicals, increased Nrf2 entering nucleus, and the expression of its downstream products heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidase 1 (NQO1) in striatum. Similar effects were obtained with the positive control drugs nimodipine or NAC.  Conclusion:  Ppt exerts a protective action against 3-NP-induced oxidative stress in the rat model of HD, which is associated with its anti-oxidant activity.
UR  - http://www.chinaphar.com/article/view/9225