Beneficial estrogen-like effects of ginsenoside Rb1, an active component of Panax ginseng, on neural 5-HT disposition and behavioral tasks in ovariectomized mice

Decreased 5-hydroxytryptamine (5-HT) concentration in the brain has been linked to central nervous system dysfunctions, especially in menopausal women. Ginsenoside Rb1, a potential phytoestrogen, has been shown to improve central nervous system dysfunctions, comparable to the estrogen treatment. To investigate the estrogen-like effects of ginsenoside Rb1 on neural 5-HT disposition and behavioral tasks, we quantified the concentrations of 5-HT and other related endogenous substances in the frontal cortex and striatum of ovariectomized mice. The activities of tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AAAD) and monoamine oxidase (MAO) were also measured to evaluate the synthesis and metabolism of neural 5-HT. Our work shows that both ginsenoside Rb1 and estradiol increased the neural 5-HT concentration. Ginsenoside Rb1 and estradiol administration resulted in elevated TPH and depressed MAO activities, indicating that modulating the synthesis and metabolism of neural 5-HT successfully elevated 5-HT concentration. Ginsenoside Rb1 and estradiol also improved object recognition and decreased immobility time in the forced swimming test. However, a pretreatment with clomiphene (an estrogen receptor antagonist) blocked the beneficial effects of ginsenoside Rb1 and estradiol, suggesting that the estrogen-like effects of ginsenoside Rb1 were estrogen receptor-dependent.