Protopanaxtriol protects against 3-nitropropionic acid-induced oxidative stress in a rat model of Huntington's disease.

Abstract

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.

• Authors: Yan Gao, Shi-feng Chu, Jian-ping Li, Zhao Zhang, Jia-qing Yan, Zhi-lin Wen, Cong-yuan Xia, Zheng Mou, Zhen-zhen Wang, Wen-bin He, Xiao-feng Guo, Gui-ning Wei, Nai-hong Chen
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 36 Issue 3 Pg. 311-22 (Mar 2015) ISSN: 1745-7254 [Electronic] United States
• PMID: 25640478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• HSP70 Heat-Shock Proteins
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Nfe2l2 protein, rat
• Nitro Compounds
• Propionates
• Reactive Oxygen Species
• Sapogenins
• protopanaxatriol
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, rat
• 3-nitropropionic acid

Topics

• Animals
• Antioxidants (pharmacology)
• Basal Ganglia (drug effects, metabolism, pathology, physiopathology)
• Behavior, Animal (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• HSP70 Heat-Shock Proteins (metabolism)
• Heme Oxygenase (Decyclizing) (metabolism)
• Humans
• Huntington Disease (chemically induced, metabolism, pathology, physiopathology, prevention & control)
• Male
• Mitochondria (drug effects, metabolism)
• Motor Activity (drug effects)
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• Nitro Compounds
• Propionates
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Sapogenins (pharmacology)
• Signal Transduction (drug effects)
• Time Factors
• Weight Loss (drug effects)