Y. Mimaki et al., ANTI-CONVULSION EFFECTS OF CHOTO-SAN, AND CHOTOKO (UNCARIAE UNCIS CAMRAMLUS) IN MICE, AND IDENTIFICATION OF THE ACTIVE PRINCIPLES, Yakugaku zasshi, 117(12), 1997, pp. 1011-1021
The crude drug, Chotoko (Uncariae Uncis cam Ramlus), the hooks of Unca
ria spp. (Rubiaceae), has been claimed to possess sedative and anti-sp
asmodic actions, and is contained in a Chinese traditional preparation
, Choto-san, as a main crude drug. Examinations were made on the anti-
convulsion effects of Choto-san and Chotoko against some animal models
of epilepsy conducted by the stimulation of drugs or electricity. Ora
l administration of the Choto-san extract to mice at the doses of 1.0
g/kg and 3.0 g/kg tended to inhibit the glutamate-induced convulsion i
n a dose-dependent manner, and the effect of the Chotoko extract at a
3.0 g/kg dose was significant, while both the extracts showed no activ
ity against the picrotoxine-induced, strychinine-induced, and electros
hock convulsions. The Choto-san preparation without Chotoko was inacti
ve, and the activity of the Chotoko extract was more potent than that
of the every crude drug comprising Choto-san, suggesting that Chotoko
plays the most important role in the Choto-san prescription and contai
ns some active compounds. Bioassay-guided fractionation of the Chotoko
extract led to the location of the active components in the less pola
r alkaloids-containing fraction, from which three indole alkaloids, ge
issoschizine methylether (1), hirusteine (2) and hirsutine (3), and an
oxyindole alkaloid, isocorynoxeine (4) were isolated and identified.
Oral administration of 1 and 2 to mice at the doses of 50, 100, and 20
0 mg/kg inhibited the glutamate-induced convulsion in a dose-dependent
manner. The effect of 3, the dihydro derivative of 2, was less potent
than those of 1 and 2. Compound 4 showed no activity at a 100 mg/kg d
ose compared with control. The above results support the Chinese herba
l description of the anti-spasmodic action of Chotoko, and show that 1
and 2 contained in Chotoko must be mainly contributed to the activity
. It is also suggested that Choto-san may be clinically available for
treatment of epilepsy.