Inhibition of stress-induced plasma corticosterone levels by ginsenosides in mice: involvement of nitric oxide

GINSENG total saponins (GTS) injected intracere-broventricularly (i.c.v.) at doses of 0.1–1 μg inhibited the i.c.v. injection stress-induced plasma corticosterone levels in mice. The inhibitory action of GTS was blocked by co-administered N-nitro-L-arginine methyl ester (L-NAME; 1.5 μg, i.c.v.), an inhibitor of nitric oxide synthase (NOS). Of the ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, 20(S)-Rg3 and 20(R)-Rg3 injected i.c.v. at doses of 0.01–1 μg, 20(S)-Rg3 and Rc significantly inhibited the i.c.v. injection stress-induced plasma corticosterone levels. The inhibitory actions of 20(S)-Rg3 and Rc were blocked by co-administered L-NAME (1.5 μg, i.c.v.). These results suggest that GTS, 20(S)-Rg3 and Rc may inhibit the i.c.v. injection stress-induced hypothalamo-pituitary-adrenal response by inducing NO production in the brain.