Zhongshi Huang1,2, Shijun Zhang1, Haiyuan Xie1, Xing Lin1, Weizhe Jiang1, Renbin Huang1

1Department of Pharmacology, Guangxi Medical University, Nanning  530021, Guangxi Zhuang Autonomous Region, China
2Department of Biochemistry, Youjiang Medical College for Nationalities, Baise  533000, Guangxi Zhuang Autonomous Region, China

Guangxi Scientific Research and Technological Development Program, No. 0630002-2A*; Doctoral Research and Innovation Program of Guangxi Graduate Education, No. 2007105981007D10*

Abstract
BACKGROUND: During onset and development of Alzheimer’s disease, β-amyloid (Aβ) precursor protein (APP), β-site amyloid precursor protein cleaving enzyme (BACE), and β-amyloid are key genes and proteins in the Aβ pathway, and over-expression of these genes can lead to Aβ deposi-tion in the brain.
OBJECTIVE: To observe the influence of Longyanshen polysaccharides on expression of BACE, APP, and Aβ in the senescence-accelerated mouse prone/8 (SAMP8) brain, and to compare these effects with huperzine A treatment.
DESIGN, TIME AND SETTING: A randomized, controlled, neurobiochemical experiment was per-formed at the Department of Pharmacology and Scientific Experimental Center of Guangxi Medical University from September 2005 to January 2008.
MATERIALS: Longyanshen polysaccharides powder was extracted from the dried slices of the medicinal plant Longyanshen. The active component, Longyanshen polysaccharides, was provided by the Department of Pharmacology, Guangxi Medical University; huperzine A was purchased from Yuzhong Drug Manufactory, China.
METHODS: Healthy SAMP8 mice were used to establish a model of Alzheimer’s disease. A total of 50 SAMP8 mice were randomly assigned to 5 groups (n = 10): SAMP8, huperzine A, low-, middle-, and high-dose polysaccharides. In addition, 10 senescence-accelerated mouse resistant 1 (SAMR1) mice were selected as normal controls. SAMP8 and SAMR1 mice were administered 30 mL/kg normal saline; the huperzine A group was administered 0.02 mg/kg huperzine A; the low-, middle-, and high-dose polysaccharides groups were respectively administered 45, 90, and 180 mg/kg Longyanshen polysaccharides. Each group was treated by intragastric administration, once per day, for 50 consecutive days.
MAIN OUTCOME MEASURES: One hour after the final administration, immunohistochemical analysis was used to determine Aβ expression in the cortex and hippocampus of SAMP8 mice. Reverse-transcription polymerase chain reaction was used to determine mRNA levels of BACE and APP in SAMP8 brain tissue.
RESULTS: Compared with the SAMR1 group, Aβ expression in the cerebral cortex and hippo-campus, as well as expression of BACE, APP mRNA in the brain was significantly increased in the SAMP8 group (P < 0.05–0.01). Compared with the SAMP8 group, Aβ expression, as well as BACE and APP mRNA expression, were significantly decreased in the cerebral cortex and hippocampus of huperzine A and low-, middle-, and high-dose polysaccharides groups (P < 0.05–0.01). In particular, the effect of high-dose polysaccharides was the most significant (P < 0.05–0.01).
CONCLUSION: Longyanshen polysaccharides reduced or inhibited over-expression of BACE, APP, and Aβ in SAMP8 mice in a dose-dependent manner, and the effect was not worse than huperzine A.

Key Words: β-amyloid; β-site amyloid precursor protein cleaving enzyme; β-amyloid precursor protein; Longyanshen polysaccharides

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