Pharmacological evidence for antidementia effect of Choto-san (Gouteng-san), a traditional Kampo medicine.

ABSTRACT

To clarify the clinical efficacy of one of the traditional medicines in the treatment of patients with vascular dementia, we investigated the pharmacological activities of Choto-san in animal models. Pretreatment with Choto-san (0.75-6.0 g/kg po), a component herb, Chotoko (75-600 mg/kg po), and indole alkaloids and phenolic fractions of Chotoko prevented ischemia-induced impairment of spatial learning behaviour in water maze performance of mice. A single administration of Choto-san (0.5 to 6.0 g/kg po) or Chotoko (Uncaria genus) produced a dose-dependent antihypertensive effect in spontaneously hypertensive rats (SHR) and partly inhibited the induction of the apoplexy in stroke-prone SHR (SHR-SP). Choto-san, Chotoko, and its phenolic constituents, (-)epicatechin and caffeic acid, significantly protected NG108-15 cells from injury induced by H(2)O(2) exposure in vitro and also inhibited lipid peroxidation in the brain homogenate. Indole alkaloids, rhynchophylline and isorhynchophylline (1-100 microM), reversibly reduced N-methyl-D-aspartate (NMDA)-induced current concentration dependently in NMDA receptor-expressed Xenopus oocytes. These results suggest that antidementia effects of Choto-san are due to antihypertensive, free radical scavenging and antiexcitotoxic effects, which are attributed at least partly to phenolic compounds and indole alkaloids contained in Chotoko.