Protective effects of Choto-san and hooks and stems of Uncaria sinensis against delayed neuronal death after transient forebrain ischemia in gerbil

Previously, we revealed that Choto-san (Diao-teng-san in Chinese), a Kampo formula, is effective on vascular dementia clinically, and the hooks and stems of Uncaria sinensis (OLIV.) HAVIL., a medicinal plant comprising Chotosan, has a neuroprotective effect in vitro. In the present study, for the purpose of clarifying their effects in vivo, we investigated whether the oral administration of Choto-san extract (CSE) or U. sinensis extract (USE) reduces delayed neuronal death following ischemia/reperfusion (i/rp) in gerbils. Transient forebrain ischemia was induced by bilateral carotid artery occlusion for 4 min, and two doses (1.0% and 3.0%) of CSE or USE were dissolved in drinking water and provided to the gerbils ad libitum from 7 days prior to i/rp until 7 days after i/rp. It was found that 1.0% and 3.0% CSE treatments significantly reduced pyramidal cell death in the hippocampal CA1 region at 7 days post i/rp. Three percent USE treatment also inhibited pyramidal cell death significantly at 7 days after i/rp. Superoxide anion and hydroxyl radical scavenging activities of the homogenized hippocampus at 7 days after i/rp in the 1.0% CSE- and 3.0% USE-treated groups were significantly enhanced compared to those of control. Further, lipid peroxide and NO₂^-/NO ₃^- levels of the homogenized hippocampus at 48h after i/rp in the 1.0% CSE- and 3.0% USE-treated groups were significantly lower than those of control. These results suggest that the oral administration of CSE or USE provides a protective effect against transient ischemia-induced delayed neuronal death by reducing oxidative damage to neurons.