Protopanaxadiol saponins in the caudexes and leaves of panax notoginseng coul d be the main constituents that contribute to its antidepressant effects

Objective: We previously found that total saponins, purified from the caudexes and leaves of Panax notoginseng (SCLPN), had antidepressant effects. In the present study, we investigated saponin monomers of SCLPN that may be the main constituents that contribute to the antidepressant effects of SCLPN.Methods: Three effective fractions of SCLPN, purified using a macroporous resin method, at doses of 50 and 100 mg/kg were tested in four different animal models of stress, including the learned helplessness test, tail suspension test, forced swim test, open field test, and reserpine-induced syndrome model. Using the same models of stress and the same doses, we then evaluated the antidepressant effects of four main and representative saponin monomers (ginsenosides Rd, Rb1 and Rg1 and notoginsenoside R1) in different effective fractions. We also examined the effects of Rd and Rb3 on monoamine neurotransmitter levels. To investigate the biotransformation of Rb1 and Rb3 orally administered in mice, Rb1 and Rb3 metabolites in blood and brain were determined by high-performance liquid chromatography.Results: Effective fraction A and C exerted greater antidepressant effects than fraction B in the behavioral tests and reserpine-induced syndrome model. Among the four saponin monomers, Rd had the strongest antidepressant effects, which improved depressive-like behavior in all four animal models of depression. We then found that Rb3 (50 and 100 mg/kg) and Rd (100 mg/kg) increased the levels of 5-hydroxytryptamine, dopamine, and norepinephrine, whereas 50 mg/kg Rd had no effect on the levels of these three neurotransmitters. Ginsenoside Rh2, C-K, and 20 (S)-protopanaxadiol saponins were detected in blood samples from mice that received Rb1 and Rb3, and protopanaxadiol saponins were found in the brain.Conclusion: The present results indicate that protopanaxadiol saponins in SCLPN have potential antidepressant-like effects.