Bioassay-guided isolation of saikosaponins with agonistic activity on 5-hydroxytryptamine 2C receptor from Bupleurum chinense and their potential use for the treatment of obesity

5-Hydroxytryptamine 2C（5-HT2C） receptor is one of the major targets of anti-obesity agents, due to its role in regulation of appetite. In the present study, the 70% EtO H extract of the roots of Bupleurum chinense was revealed to have agonistic activity on 5-HT2 C receptor, and the subsequent bioassay-guided isolation led to identification of several saikosaponins as the active constituents with 5-HT2 C receptor agonistic activity in vitro and anti-obesity activity in vivo. The new compound, 22-oxosaikosaponin d（1）, was determined by extensive spectroscopic analyses（HR-ESI-MS, IR, and 1D and 2D NMR）. The primary structure-activity relationship study suggested that the intramolecular ether bond between C-13 and C-28 and the number of sugars at C-3 position were closely related to the 5-HT2 C receptor agonistic activity. Saikosaponin a（3）, the main saponin in B. chinense, showed obviously agonistic activity on 5-HT2 C receptor with an EC50 value of 21.08 ± 0.33 μmol×L~（–1） in vitro and could reduce food intake by 39.1% and 69.2%, and weight gain by 13.6% and 16.4%, respectively, at 3.0 and 6.0 mg×kg~（–1） in vivo. This investigation provided valuable information for the potential use of B. chinense as anti-obesity agent.