Bupleurum chinense Roots: a Bioactivity-Guided Approach toward Saponin-Type NF-κB Inhibitors.

The roots of Bupleurum chinense have a long history in traditional medicine to treat infectious diseases and inflammatory disorders. Two major compounds, saikosaponins A and D, were reported to exert potent anti-inflammatory activity by inhibiting NF- κ B. In the present study, we isolated new saikosaponin analogues from the roots of B. chinese interfering with NF- κ B activity in vitro . The methanol-soluble fraction of the dichloromethane extract of Radix Bupleuri was subjected to activity-guided isolation yielding 18 compounds, including triterpenoids and polyacetylenes. Their structures were determined by spectroscopic methods as saikogenin D ( 1 ), prosaikogenin D ( 2 ), saikosaponins B2 ( 3 ), W ( 4 ), B1 ( 5 ), Y ( 6 ), D ( 7 ), A ( 8 ), E ( 9 ), B4 ( 10 ), B3 ( 11 ), and T ( 12 ), saikodiyne A ( 13 ), D ( 14 ), E ( 15 ) and F ( 16 ), falcarindiol ( 17 ), and 1-linoleoyl-sn-glycero-3-phosphorylcholine ( 18 ). Among them, 4, 15 , and 16 are new compounds, whereas 6, previously described as a semi-synthetic compound, is isolated from a natural source for the first time, and 13 - 17 are the first reports of polyacetylenes from this plant. Nine saponins/triterpenoids were tested for inhibition of NF- κ B signaling in a cell-based NF- κ B-dependent luciferase reporter gene model in vitro . Five of them ( 1, 2, 4, 6 , and 8 ) showed strong (> 50%, at 30 µM) NF- κ B inhibition, but also varying degrees of cytotoxicity, with compounds 1 and 4 (showing no significant cytotoxicity) presenting IC50 values of 14.0 µM and 14.1 µM in the cell-based assay, respectively.