Isolation of saponins with the inhibitory effect on nitric oxide, prostaglandin E₂ and tumor necrosis factor-α production from pleurospermum kamtschaticum

As an attempt to search for bioactive natural products exerting antiinflammatory activity, we have isolated two saponins were isolated from the aerial portion of Pleurospermum kamtschaticum (Umbelliferae) by nitrite assay activity-directed chromatographic fractionation. They were identified as saikogenin F 3-O-{β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl- (1→3)]-β-D-fucopyranoside} (buddlejasaponin IV, 1) and 3β,16β,23,28-tetrahydroxy-11α-methoxyolean-12-ene 3-O-{β-D-glucopyranosyl(1→2)-[β-D-glucopyranosyl(1→3)] -β-D-fucopyranoside} (buddlejasaponin IVa, 2). Compound 1 significantly inhibited nitric oxide (NO) production, and it also significantly decreased prostaglandin E₂ (PGE₂) and tumor necrosis factor-α (TNF-α) release in the lipopolysaccharide (LPS)-activated macrophage Raw 264.7 cells whereas compound 2 was much less active. Saikogenin A (3) and -H (4) were obtained by hydrolyzing 1 and 2. Although these sapogenin showed strong NO inhibition, these effects were caused by the cytotoxic effect on Raw 264.7 cells. These results supported the notion that buddlejasaponin IV is a major inhibitors of NO, PGE₂ and TNF-α production in P. kamtschaticum.