To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220？g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400？mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required. 1. Background Dementia, a serious loss of global cognitive ability including the impairments of memory, attention, language, and problem solving, is continually growing worldwide accompanied with the increased elderly population. It has been estimated that there are approximately 35.6 million people with dementia worldwide [1]. Due to the rapidly growth of prevalence, high expenditure cost, and unsatisfactory outcomes of therapeutic strategy, dementia has been recognized as one of the major medical and social challenges especially in developing countries [2]. Recent findings have shown that the age-related cognitive dysfunction occurs as a result of oxidative stress elevation in the brain [3], hippocampal atrophy [4], and the disturbances of neurotransmission, especially cholinergic transmission. Therefore, the modulation of cholinergic function becomes the approach to dementia treatment. However, most drugs still induce adverse effects [5]. This disadvantage consequently motivates research effort to find out novel protective agent against dementia. Herbal medicine has long been used to treat numerous ailments. Moreover, the “Green” movement has driven the attitude changes of the general population to
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