Bene fi cial effects of asiaticoside on cognitive de fi cits 2 in senescence - accelerated mice

12 Article history: 13 Received 25 February 2013 14 Accepted in revised form 19 March 2013 15 Available online xxxx 6 The effect of asiaticoside isolated from Hydrocotyle sibthorpioides (AHS) on the promotion of 7 cognition in senescence-accelerated mice (SAMP) was evaluated. Six-month old male SAMP8 18 micewere orally administered 20, 40 or 80 mg/kg AHS daily for threemonths. SAMR1mice were 19 used as a “normal aging” control. The results showed that treatment with AHS significantly 20 improved learning and memory abilities in behavioral tests. AHS-treated mice showed higher 21 antioxidant enzyme activity and lower lipid oxidation in serum compared with untreated SAMP8 22 mice. Mechanistically, studies showed that AHS markedly reduced the content and deposition of 23 β-amyloid peptide (Aβ) by inhibiting the expression of mRNA for amyloid protein precursor, 24 β-site amyloid cleaving enzyme-1 and cathepsin B and promoting the expression of mRNA for 25 neprilysin and insulin degrading enzyme. In addition, AHS significantly increased the expression 26 of plasticity-related proteins including postsynaptic density-95, phosphor-N-methyl-D-aspartate 27 receptor 1, phospho-calcium–calmodulin dependent kinase II, phospho-protein kinase A Catalyticβ 28 subunit, protein kinase Cγ subunit, phospho-CREB and brain derived neurotrophic factor. 29 Furthermore, AHS increased the levels of acetylcholine (Ach), but decreased cholinesterase (AchE) 30 activity. These results demonstrated that AHS administration may prevent spatial learning and 31 memory decline by scavenging free radicals, up-regulating the activity of antioxidant enzymes, 32 decreasing the level of Aβ, ameliorating dysfunction in synaptic plasticity, and reversing abnormal 33 changes in Ach level and AchE activity. Thus, AHS should be developed as a new drug to prevent 34 age-related cognitive deficits. 35 © 2013 Published by Elsevier B.V. 36