Magnolol(5,5Ј-di-2-propenyl-1,1Ј-biphenyl-2,2Ј-diol), one of the main constituents in the stem bark of Magnolia obovata THUNB and Magnolia officinalis RHED, 1,2) has been used as a traditional Chinese medicine and has a wide spectrum of pharmacological activities.3) In the central nervous system, magnolol has been reported to increase extracellular acetylcholine release in rat hippocampus, 4) to decrease the release of serotonin, dopamine, and norepinephrine in rat hypothalamus, 5) to reduce the increased production of prostaglandin E 2 caused by chemical hypoxia in neurons, 6) and to interact with g-aminobutyric acid (GABA) receptors in rat brain. 7) In addition, we reported that magnolol had neurotrophic properties, such as promotion of neurite outgrowth and neuronal survival under serum-deprived conditions in cultured rat cortical neurons. 8) However, these actions have not been demonstrated in in vivo experiments.Senescence-accelerated mice (SAM) are selected by brother/sister mating of AKR/J mice, and are characterized by rapid accumulation of senile features and shortened life span (1-1.5 years compared to 2-2.5 years in control animals).9) SAM consist of nine inbred strains of accelerated senescence-prone mice (SAMP) and three of accelerated senescence-resistant mice (SAMR), the latter of which show normal aging. Until the age of 4 months, SAMP1 animals do not differ from SAMR1 either behaviorally or morphologically, but later they begin to rapidly accumulate senile changes. This results in disordering of their behavioral reactions and cognitive brain functions (orientation ability and learning capacity are particularly decreased) and appearance of age-specific morphological changes (lordokyphosis, loss of hair, frequent eye cataract, and mucosal inflammation).
10)Kawaguchi et al. reported that SAMP1TA/Ngs, a substrain of SAMP1, manifests learning disturbance at 7 months of age on a step-down passive avoidance test.
11)This study was undertaken to estimate the neurite outgrowth and neuronal survival effect of magnolol on the senescence-related morphological changes on the density of dendrite in the stratum radiatum of the hippocampal CA1 area, which plays an important role in learning and memory, in SAMP1 mice.
MATERIALS AND METHODSMaterials Magnolol (Fig. 1) was isolated from the cortex of M. officinalis RHED. The purity was determined by a high-performance liquid chromatography (single peak) and by nuclear magnetic resonance spectra.Animal Experiments All experiments were conducted in accordance with the Guiding Principles for Care and Use of Laboratory Animals approved by the Japanese Pharmacological Society. The substrains of SAM, SAMP1, and SAMR1 were originally obtained from the Institute for Frontier Medical Sciences in Kyoto University and bred in the Faculty of Health and Welfare Science in Okayama Prefectural University. Mice were kept in an air conditioned room maintained at 25Ϯ1°C with humidity of 55%Ϯ5%. The animals were given food and water ad libitum. Two-to 10-month-old female SAMP1 and SA...