| 總結: | Dementia is a general term to describe decline of mental ability associated with
cognitive impairment, losing memory or other thinking skills that interfere with
occupational functioning and usual social activities. The most common type of
dementia is Alzheimer’s disease (AD) which is a neurodegenerative disease related to
cognitive and behavioural impairments. The major AD drugs are known as
acetylcholinesterase inhibitors (AChEI) which are not acceptable in a wide range of
patients due to resistance, adverse effect, and poor efficacy. Based on recent studies,
herbal medicine such as zerumbone (2,6,9,9-tetramethyl-[2E,6E,10E]-cycloundeca-
2,6,10-trien-1-one) which is a sesquiterpenoid compound, could be a new source for
inhibition of AChE enzyme. Zerumbone was first isolated from the rhizomes oil of
Zingiber zerumbet Smith, in 1956. It has the potential for treatment of cancers,
leukemia and virus infection. In this study, scopolamine which is a muscarinic
antagonist drug was used to induce some dementia-like behaviours in rats and the
effect of zerumbone (1 and 10mg/kg) was investigated through some behavioural and
biochemical experiments. All the results were expressed as mean ± standard error of
mean (SEM) and analyzed using one-way analysis of variance (ANOVA) followed by
Tukey's post hoc analysis. p<0.05 was considered statistically significant. Behavioural
assessments such as open field tests, elevated plus maze, and Morris water maze were
performed to assess general locomotors activity, anxiety-like behaviours, and learning
and memory processes respectively, in Sprague-Dawley rats pre-treated with
scopolamine. Based on the results obtained, zerumbone 1 mg/kg significantly reduced
total activity, stereotype, and total distance travelled in the open field arena. Moreover,
zerumbone 1 and 10mg/kg, respectively showed high percent of time spent in open
arms; and increased number and percent of entry to open arms, in the elevated plus
maze. Also, in the Morris water maze, zerumbone 1 and 10mg/kg showed learning
improvement by significant reduction in mean escape latency time. Interestingly, single
administration of zerumbone (1 and 10mg/kg) reversed the hyperactivity, anxiety-like
behaviour, and learning impairment effects of scopolamine to normal condition.
Biochemical experiments have been done on the brain samples which were sectioned to
three parts (prefrontal cortex, hippocampus, and cortex) and prepared for acetyl
cholinesterase (ACHE) enzyme activity and choline acetyltransferase (ChAT) protein
expression. AChE enzyme activity is significantly reduced by zerumbone 1mg/kg in
the hippocampus brain samples compared to all groups. On the other hand, lower dose
of zerumbone reversed the effect of scopolamine by decreasing AChE enzyme activity.
Western blotting was also used to determine ChAT protein expression among all
groups and it was concluded that there isn’t any significant differences between all
groups and both dosage of zerumbone were not effective towards ChAT protein
expression. In conclusion, zerumbone showed improvement in learning process while
reduced hyperactivity, anxiety/depression, and AChE enzyme activity in scopolamine
pre-treated rats. Thus, zerumbone could be a great candidate for treatment of dementialike
behaviour. Although, more research need to be done to find out its mechanism of
action.
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