Inhibitory effect of sesquiterpene lactones and the sesquiterpene alcohol aromadendrane-4β,10α-diol on memory impairment in a mouse model of Alzheimer

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• 作者：Solomon K.S. Amoah^c ; Maria Tereza Dalla Vecchia^a ; Beatriz Pedrini^a ; Gabriela Lazzarotto Carnhelutti^a ; Ana Elisa Gonç ; alves^b ; Diogo Adolfo dos Santos^b ; Maique W. Biavatti^c ; ^{maique.biavatti@ufsc.br" class="auth_mail" title="E-mail the corresponding author} ; Má ; rcia Maria de Souza^b
• 关键词：Hedyosmum brasiliense ; Sesquiterpene lactones ; Sesquiterpene alcohol ; Alzheimer
• 刊名：European Journal of Pharmacology
• 出版年：2015
• 出版时间：15 December 2015
• 年：2015
• 卷：769
• 期：Complete
• 页码：195-202
• 全文大小：789 K

文摘

Alzheimer's disease (AD), a progressive neurodegenerative disorder of the aged brain with no known cause or cures, has become a major medical and social problem for industrialized countries. Cerebral deposition of amyloid-β peptide (Aβ) is a critical feature of AD. The use of medicinal plants as an alternative form of prevention, or even as a possible treatment of AD, is therefore interesting areas of research. Sesquiterpene lactones and a sesquiterpene alcohol are compounds found in H. brasiliense that have several anti-oxidative and anti-inflammatory effects. In the present study, we investigated whether these compounds have neuroprotective effects in an amyloid-β peptide-induced Alzheimer's disease mouse model. Mice were injected with Aβ_1-42 peptide intracerebroventricularly and were subsequently injected (i.c.v.) with 1 µg/site of IGM-A (15-acetoxy-isogermafurenolide), IGM-H (15-hydroxy-isogermafurenolide), PDA (Podoandin), EHP (1,2-epoxy-10α-hydroxy-podoandin), HDS (13-hydroxy-8,9-dehydroshizukanolide), and ARD (aromadendrane-4β,10α-diol). Seven days after treatments the animals had their memory tested in the inhibitory avoidance. After the behavioral testing of animals the brains were removed and subjected to biochemical tests for oxidative stress. The results showed that ARD, HDS and PDA significantly ameliorated the Aβ_1-42 peptide-induced memory impairment in the passive avoidance task (P<0.05). In addition, GSH activity was increased while the TBARS levels were decreased by treatment with these compounds. These results suggest that these compounds inhibit the cognitive deficit of animals induced peptide amyloid and may be potential candidates for Alzheimer's disease therapy.