Biol. Pharm. Bull. 29(7) 1431—1435 (2006)

tients are impairment in cognitive performances such as attention, learning and memory, and change of cholinergic markers, including levels of acetylcholine (ACh) and choline acetyltransferase (ChAT). Since cholinergic deficits are found to be associated with cognitive decline or dementia, increase of the central cholinergic system by selective inhibition of cholinesterase is one of the more promising current therapeutic tools for treating AD. Cholinergic neurons originating in the nucleus basalis of Meynert (NBM) and the medial septum (MS) project to areas such as the cortex and hippocampus, where play the role of ACh in cognition. Lesioning these pathways in rodents decreases ACh release and produces an impairment of memory-related task performance. The observations that impairment can be reversed by cholinergic agonists suggest that the cholinergic system is damaged in AD and that drugs which induce cholinergic activity may treat AD. For the testing of putative, cognitionenhancing agents, the establishment and standardization of animal cognitive deficit models are required. Lesion of the MS in animals has been widely approved as an animal model of memory loss. Cognitive dysfunctions after lesioning the MS are mainly considered to be due to deafferentiation of the hippocampus, which plays a major role in learning and memory. Coordinated action of acetylcholine and glutamate is important for the production of memory. ACh facilitates glutamate activity by coordinating the states of acquisition and recall in the cortex and hippocampus and the activation of N-methyl-D-aspartate (NMDA) receptors is a prerequisite for the stimulation of long-term potentiation (LTP) in the septohippocampal cholinergic system, which is involved in the memory performance of rats in some learning tasks that depend on hippocampal functions. Ibotenic acid stimulates neuronal necrosis by a hyperstimulation of the NMDA glutamate receptors leading to calcium overload. Its excitotoxic properties are confined to somata of neurons and therefore axons and blood vessels that course through the target areas remain intact. Injections of ibotenic acid into the MS in rats result in a significant deficit in the Morris water maze, which has been designed to measure spatial learning and memory, and provide a more advanced stage of the neurodegeneration as an animal model of AD. Herbal medicines, such as Ginko biloba, Ginseng, or Melisa officinalis, have been commonly used as memory or cognition enhancers. The effects of these enhancers have been demonstrated scientifically. Yukmijihwang-tang (YMJ or Luweidihuang-wang) is another memory or cognition enhancer. YMJ is composed of 6 herbal medicines, including steamed Rehmannia radix, Discoreae radix, Corni fructus, Hoelen, Mountain cortex radicis, and Alismatis radix. YMJ has long been applied in the treatment of diabetes mellitus and neurosis. Ancient Chinese herbal textbooks also refer to YMJ as an anti-aging prescription. A series of modern medical reports show that YMJ has anti-aging effects in vivo and in vitro. In addition, antioxidant and free radical scavenging activities of YMJ have been clinically demonstrated. Besides its anti-aging effects, Wei have reported that YMJ prevents the deterioration of learning and memory ability in senescent accelerated mice and hydrocortisone-treated mice. It is also reported that YMJ reverses scopolamine-induced and p-chloroamphetamine-induced amnesia in rats. In addition, our unpublished data shows that YMJ derivatives (YMJd), including Lycii fructus, enhance memory retention by protecting neuronal cells from attack by reactive oxygen species (data not shown). Our previous results have revealed that YMJd has a significant effect on memory enhancement and the expression of genes associated not only with the prevention of neuronal degeneration but also with neuronal July 2006 1431 Biol. Pharm. Bull. 29(7) 1431—1435 (2006)