Bupleurum chinenseRoots: a Bioactivity-Guided Approach toward Saponin-Type NF-κB Inhibitors

摘要

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 B 2(>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>16are new compounds, whereas>6,previously described as a semi-synthetic compound, is isolated from a natural source for the first time, and>13–>17are the first reports of polyacetylenes from this plant. Nine saponins/triterpenoids were tested for inhibition of NF-κB signaling in a cell-based NF-κB-dependent luciferase reporter gene modelin vitro. Five of them (>1, 2, 4, 6, and>8) showed strong (> 50%, at 30 µM) NF-κB inhibition, but also varying degrees of cytotoxicity, with compounds>1and>4(showing no significant cytotoxicity) presenting IC50values of 14.0 µM and 14.1 µM in the cell-based assay, respectively.