Pharmacological evidence for antidementia effect of Choto-san (Gouteng-san), a traditional Kampo medicine.
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.
Watanabe
Hiroshi
H
Department of Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan. hwatanabe@ms.toyama-mpu.ac.jp
Zhao
Qi
Q
Matsumoto
Kinzo
K
Tohda
Michihisa
M
Murakami
Yukihisa
Y
Zhang
Shao-Hui
SH
Kang
Tae-Hyun
TH
Mahakunakorn
Pramote
P
Maruyama
Yukiko
Y
Sakakibara
Iwao
I
Aimi
Norio
N
Takayama
Hiromitsu
H
D000818:Animals; D002460:Cell Line; D003704:Dementia / Q000188:drug therapy* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D020835:Medicine, Kampo; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014981:Xenopus
D004365:Drugs, Chinese Herbal; D016166:Free Radical Scavengers; C120250:choto-san