ABSTRACT
OBJECTIVES: The present study was designed to investigate the effect of ginseng saponin and its major active metabolite on the HPA axis under acute stress-i.c.v. injection stress, and immobilization stress, and to examine whether nitric oxide is involved in the mechanism of ginseng saponin on the HPA axis under acute stress. METHODS: In the experiment to study the effect of ginseng on HPA axis during stress, various dose of GTS were injected intracerebroventricularly(i.c.v.) or intraperitoneally(i.p.). Plasma corticosterone levels were measured 30 min after the i.c.v. injection stress. Immobilization stress was applied for 30 min and then blood was cellected for the assays of plasma corticosterone levels immediately after the completion of immobilization stress. To determine the active ginsenosides that can affect the stressinduced plasma corticosterone levels, various dose of each gisendosides(Rb1, Rb2, Rc, Re, Rf, Rg1, 20(S)-Rg3, and 20(R)-Rg3) were injected i.c.v. or i.p.. In the experiment to determine the involvement of the nitric oxide in the inhibitory effect of ginseng on the HPA, NG-Nitro-L-arginine methyl ester(L-NAME) and ginsenosides were coadministered i.c.v. or i.p., and plasma corticosterone levels were measured 30 min after stress was applied. RESULTS: First, the present study showed that ginseng total saponin, ginsenoside Rg3(S form), and ginsenoside Rc administered i.c.v. attenuated the intracerebroventricular injection stress-induced increase in plasma corticosterone levels, and these effects were removed by nitric oxide co-injection. Second, ginseng total saponin and ginsenoside Rc administered i.p. attenuated the immobilization stress-induced increase in plasma corticosterone levels, but ginsenoside Rg3(S form) did not attenuate the immobilization stress-induced increase in plasma corticosterone levels. The attenuative effects of ginseng total saponin and ginsenoside Rc in the immobilization stress-induced increase in plasma corticosterone levels were not affected by L-NAME co-injection. CONCLUSION: This study suggests that ginseng saponin attenuated stress-induced increase in plasma corticosterone levels and these effects were mediated by different mechanisms according to the components of ginseng saponin, and routes of administration.