Involvement of serotonergic, noradrenergic and dopaminergic systems in the antidepressant-like effect of ginsenoside Rb1, a major active ingredient of Panax ginseng CA Meyer

Ethnopharmacology relevance: Ginsenoside Rb1, a 20 (S)-protopanaxadiol, is a major active ingredient of Panax ginseng C.A. Meyer, which as the King of Chinese herbs, has been wildly used for the treatment of central nervous system diseases. Previous studies have shown that 20 (S)-protopanaxadiol possesses a novel antidepressant-like effect in the treatment of depression, whereas ginsenoside Rb1 in depression has been rarely reported. Aim of the review: The present study was to investigate the antidepressant-like effect of ginsenoside Rb1 and its relevant mechanisms. Materials and methods: The whole experiment was divided into two parts: one part we examined the antidepressant-like effect of ginsenoside Rb1 with open-field test (OFT), tail suspension test (TST), forced swim test (FST), 5-HTP induced head-twitch and reserpine response in mice, another part we used chronic unpredicted mild stress (CUMS) model to further explore the antidepressant-like effect of ginsenoside Rb1 with caffeine, fluoxetine and p-Chlorophenylalanine (PCPA) in rats. Furthermore, the levels of monoamine neurotransmitters of NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, HVA were all measured by ELISA kits after the CUMS protocol. Results: Our data indicated that 7 days treatment with ginsenoside Rb1 (4, 8, 10 mg/kg, p.o.) significantly decreased immobility time in the FST and TST in mice, and played important roles in mice which were induced by 5-HTP (200 mg/kg, i.p.) and reserpine (4 mg/kg, i.p.). On the basis of CUMS model, 21 days treatment with ginsenoside Rbl not only had effective interactions with caffeine (5 mg/kg, i.p.), fluoxetine (1 mg/kg, i.p.) and PCPA (100 mg/kg, i.p.), but also significantly up-regulated the 5-HT, 5-HIAA, NE and DA levels in CUMS rats' brain, whereas HVA and DOPAC had no significant difference. Moreover, there was no alteration in spontaneous locomotion in any experimental group. Conclusions: These results suggest that ginsenoside Rb1 exhibits significant antidepressant-like effect in behavioral tests, chronic animal model and drug interactions, its mechanisms mainly mediated by central neurotransmitters of serotonergic, noradrenergic and dopaminergic systems.