Isolation and evaluation of kaempferol glycosides from the fern Neocheiropteris palmatopedata

Six kaempferol glycosides including three hitherto unknown compounds (1–3) were isolated from the roots of the fern Neocheiropteris palmatopedata. Compounds 1 and 2 were determined to possess an unusual sugar moiety containing a 4,4-dimethyl-3-oxo-butoxy substituent group, respectively. The isolates were evaluated for their cancer chemopreventive potential based on their ability to inhibit tumor necrosis factor-α-induced induced NF-κB, nitric oxide (NO) production, aromatase, quinone reductase 2 (QR2) and COX-1/-2 activities. Kaempferol glycosides, named palmatosides A ( 1), B ( 2) and C ( 3), together with three known kaempferol glycosides, multiflorins A ( 4) and B ( 5), and afzelin ( 6), were isolated from the roots of the fern Neocheiropteris palmatopedata. Palmatosides A ( 1) and B ( 2) each possessed an unusual sugar moiety containing a 4,4-dimethyl-3-oxo-butoxy substituent group. The isolated compounds were evaluated for their cancer chemopreventive potential based on their ability to inhibit tumor necrosis factor alpha (TNF-α)-induced NF-κB activity, nitric oxide (NO) production, aromatase, quinone reductase 2 (QR2) and COX-1/-2 activities. Palmatosides B ( 2) and C ( 3) inhibited TNF-α-induced NF-κB activity with IC 50 values of 15.7 and 24.1 μM, respectively; multiflorin A ( 4) inhibited aromatase enzyme with an IC 50 value of 15.5 μM; afzelin ( 6) showed 68.3% inhibition against QR2 at a concentration of 11.5 μg/ml; palmatoside A ( 1) showed 52% inhibition against COX-1 enzyme at a concentration of 10 μg/ml; and multiflorin B ( 5) showed 52% inhibition against nitric oxide production at a concentration of 20 μg/ml. In addition, compounds 3– 6 were shown to bind QR2 enzyme using LC–MS ultrafiltration binding assay.