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Gypenosides improve cognitive impairment induced by chronic cerebral hypoperfusion in rats by suppressing oxidative stress and astrocytic activation

Zhang, Guang-Lina,c; Deng, Jian-Pinga; Wang, Ben-Hanc; Zhao, Zhen-Weia; Li, Jianga; Gao, Lia; Liu, Bo-Linb; Xong, Jia-Ruic; Guo, Xiao-Dongc; Yan, Zhi-Qianga; Gao, Guo-Donga

doi: 10.1097/FBP.0b013e32834afef9
Original Articles

Gypenosides (GP), the saponin extract derived from the Gynostemma pentaphyllum Makino, a widely reputed medicinal plant in China, has been reported to have some neuroprotective effects. We used a rat model of chronic cerebral hypoperfusion to investigate the protective effects of GP on the cortex and hippocampal CA1 region and the underlying mechanisms for its inhibition of cognitive decline. Daily doses of 100 and 200 mg/kg GP were orally administered to adult male Sprague–Dawley rats for 61 days after inducing cerebral hypoperfusion experimentally, and spatial learning and memory were assessed using the Morris water maze. Antioxidative capability was measured biochemically. The levels of lipid peroxidation and oxidative DNA damage were assessed by immunohistochemical staining for 4-hydroxynonenal and 8-hydroxy-2′-deoxyguanosine, respectively. Activated astrocytes were assessed by immunohistochemical staining and western blotting with GFAP antibodies. Rats receiving 200 mg/kg GP had better spatial learning and memory than saline-treated rats. GP 200 mg/kg/day were found to markedly enhance antioxidant abilities, decrease lipid peroxide products and oxidative DNA damage, and reduce the activation of inflammatory astrocytes. However, GP 100 mg/kg had no significant effects. GP may have therapeutic potential for the treatment of dementia induced by chronic cerebral hypoperfusion and further evaluation is warranted.

aInstitute for Functional Neurosurgery PLA and Institute for Functional Brain Disorders, Tang Du Hospital

bDepartment of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, The Fourth Military Medical University, Xi'an

cDepartment of Neurosurgery, 153rd Hospital of PLA, Zhengzhou, People's Republic of China

Guang-Lin Zhang, Jian-Ping Deng, and Ben-Han Wang contributed equally to this study.

Correspondence to Dr Guo-Dong Gao, Institute for Functional Neurosurgery PLA and Institute for Functional Brain Disorders, Tang Du Hospital, The Fourth Military Medical University, Xinsi Road, Baqiao District, Xi'an 710038, P.R. China e-mail: zglin127s@163.com

Received March 30, 2011

Accepted June 19, 2011

© 2011 Lippincott Williams & Wilkins, Inc.