Effects of Yukmijihwang-tang derivatives (YMJd) on ibotenic acid-induced amnesia in the rat

Our previous results have revealed that Yukmijihwang-tang derivatives (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 growth events [1] and also demonstrated that YMJd significantly enhances cognitive abilities in normal human subjects [2]. However, there have been few reported studies on accessing learning and memory enhancement triggered by treatment with YMJd in dementia animal models. Thus, the present study investigates the effects of YMJd on learning and memory through the Morris water maze task and the central cholinergic system of rats with excitotoxic medial septum (MS) lesions. Ibotenic acid lesions of the MS showed the impaired performance in the Morris water maze test and severe cell losses in the MS, as indicated by decreased choline acetyltransferase-immunoreactivity in the medial septum. Daily administrations of YMJd (100mg/kg, i.p.) for 21 consecutive days produced significant reversals of ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of choline acetyltransferase (ChAT) immunoreactivity in the MS induced by ibotenic acid. These results suggest that impairments of spatial learning and memory might be attributable to the degeneration of septohippocampal cholinergic (SHC) neurons and that YMJd treatment ameliorated learning and memory deficits partly due through neuroprotective effects on the central acetylcholine system. Our studies suggest that YMJd might be useful in the treatment of Alzheimer's disease.

Acknowledgements: This study was supported by a grant of the Oriental Medicine R&D Project, Ministry of Health & Welfare, Republic of Korea (B061016)

References: 1. Rho, S. et al. (2005) Biol. Pharm. Bull. 28:87–93

2. Park, E. et al. (2005) The American Journal of Chinese Medicine 33:107–115