Pharmacol Biochem Behav. 2003 Jun; 75(3): 635-43.

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

Watanabe H, Zhao Q, Matsumoto K, Tohda M, Murakami Y, Zhang SH, Kang TH, Mahakunakorn P, Maruyama Y, Sakakibara I, Aimi N, Takayama H.

Department of Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan. hwatanabe@ms.toyama-mpu.ac.jp

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.