Evaluation of the protective effects of alkaloids isolated from the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death in cultured cerebellar granule cells from rats

被引:149
作者
Shimada, Y
Goto, H
Itoh, T
Sakakibara, I
Kubo, M
Sasaki, H
Terasawa, K
机构
[1] Toyama Med & Pharmaceut Univ, Fac Med, Dept Japanese Oriental Med, Toyama 9300194, Japan
[2] Tsumura Cent Res Labs, Ami, Ibaraki 3001192, Japan
关键词
D O I
10.1211/0022357991772853
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We have previously shown that an aqueous extract of the hooks and stems of Uncaria sinensis (Oliv.) Havil., Uncariae Uncus Cum Ramulusis, protects against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx. Because it is not known which components of Uncaria sinensis are active, in this study we have evaluated, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) staining, the neuroprotective effects of the oxyindole alkaloids corynoxeine, rhynchophylline, isorhynchophylline and isocorynoxeine, and the indole alkaloids geissoschizine methyl ether, hirsuteine and hirsutine, isolated from the hooks and stems of Uncaria sinensis, on glutamate-induced cell death. We also investigated the inhibitory effects of the compounds on Ca-45(2+) influx in cultured rat cerebellar granule cells. Cell viability evaluated by the MTT assay was significantly increased by application of rhynchophylline (10(-3) M), isorhynchophylline (10(-4)-10(-3)M), isocorynoxeine (10(-4)-10(-3)M), hirsuteine (10(-4)-3 x 10(-4)M) or hirsutine (10(-4)-3 x 10(-4)M) compared with exposure to glutamate only, with the effect of isorhynchophylline being the strongest. The increased Ca-45(2+) influx into cells induced by glutamate was significantly inhibited by administration of rhynchophylline (10(-3) M), isorhynchophylline (3 x 10(-4)-10(-3)M), isocorynoxeine (3x10(-4)-10(-3) M), geissoschizine methyl ether (10(-3) M), hirsuteine (3 x 10(-4)-10(-3) M) or hirsutine (3 x 10(-4)-10(-3) M). These results suggest that oxyindole alkaloids such as isorhynchophylline, isocorynoxeine and rhynchophylline and indole alkaloids such as hirsuteine and hirsutine are the active components of the hooks and stems of Uncaria sinensis which protect against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx.
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页码:715 / 722
页数:8
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