NF-kappaB inhibitory activity of cyclitols isolated from Hancornia speciosa.

Hancornia speciosa Gomes (Apocynaceae) is a Brazilian plant traditionally employed to treat inflammatory conditions, among other uses. The chemopreventive effect of an ethanol extract from H. speciosa leaves (EHS) was evaluated in a battery of in vitro tests [inhibition of aromatase, NF-kappaB and ornithine decarboxylase (ODC), antioxidant response elements (ARE) induction and cell proliferation assays]. Bioassay-directed fractionation of EHS following by inhibition of 12-O-tetradecanoyl-13-acetate (TPA)-mediated NF-kB activation led to the isolation of the cyclitols quinic acid (1) (85.0+/-12.3 microM) and l-(+)-bornesitol (2) (IC(50)=27.5+/-3.8 microM), along with rutin (26.8+/-6.3 microM). Based on these lead compounds, the cyclitols per-O-acetyl-1l-(+)-bornesitol (3) (IC(50)=38.4+/-6.2 microM), myo-inositol (4) (>180.2 microM), scyllo-inositol (5) (83.0+/-13.7 microM) and beta-d-galactoside-myo-inositol (6) (52.4+/-8.4 microM) were evaluated in the assay, but found to be somewhat less active than 1 and 2. None of the compounds was active in the ARE, aromatase or ODC assays and did not inhibit proliferation of MCF-7, LNCaP, HepG2 or LU-1 cell lines at a final concentration of 20 microg/ml (equivalent to 104.07-32.76 microM).This work identifies l-(+)-bornesitol, quinic acid and rutin as NF-kappaB inhibitors of H. speciosa and suggests cyclitols, in addition to myo-inositol, are potentially useful as chemopreventive agents.