Structural implication in cytotoxic effects of sterols from Sellaginella tamariscina.

A bioassay-guided fractionation of the CH(2)Cl(2) extract of Selaginella tamariscina yielded six sterols 1-6 such as (4α, 5α)-4, 14-dimethylcholest-8-en-3-one (1), ergosta-4, 6, 8(14), 22-tetraene-3-one (2), ergosterol endoperoxide (3), 7ß-hydroxycholesterol (4), 7ß-hydroxysitosterol (5), and 7α-hydroxysitosterol (6). The structures of isolated compounds were determined using spectroscopic methods. Among these isolates, compounds 2-5 showed potent cytotoxicity against five human tumor cells, while compounds 1 and 6 did not. In the case of compounds 1 and 2, 3-oxo sterol derivatives, compound 1 was inactive, but compound 2 showed potent cytotoxicity. In addition, compound 5 exhibited potent cytotxicity, but, compound 6 which is the 7-epimer of compound 5 was weakly active against tumor cell lines. Therefore, in the case of oxysterol derivatives, the cytotoxicity appeared to be affected by the structural differences, i.e. the configuration of hydroxyl group and the number of conjugated double bond. Taken all together, the present study isolated six sterols from S. tamariscina for the first time based on a bioassay-guided fractionation and indicated that isolated oxysterols could exhibit the cytotoxic effects against tumor cells, suggesting that S. tamariscina might be a promising candidate for the development of anticancer agents.

A new furofuran lignan from Geranium thunbergii Sieb. et Zucc.

A new furofuran lignan, 4-hydroxykobusin (3), together with known lignans, kobusin (1), and 7,7'-dihydroxybursherenin (2), were isolated from the whole plant of Geranium thunbergii Sieb. et Zucc (Geraniaceae). The structures were determined based on the spectral data and a comparison with the published data. This is the first report of the presence of furofuran lignan in Geranium species.

Effects of phenylethanoid glycosides from Digitalis purpurea L. on the expression of inducible nitric oxide synthase.

We have isolated four different phenylethanoid glycosides (purpureaside A, desrhamnosyl acteoside, calceolarioside B and plantainoside D) from the leaves of Digitalis purpurea (foxglove). The effects of these glycosides on activator protein-1 (AP-1)-mediated inducible nitric oxide synthase (iNOS) gene expression in the Raw264.7 macrophage cell line have been studied. Of these four glycosides, purpureaside A potently inhibited iNOS induction by lipopolysaccharide (LPS). Increase in iNOS mRNA by LPS was completely suppressed by purpureaside A. Purpureaside A did not significantly affect LPS-inducible nuclear factor-kappaB (NF-kappaB) activation or the nuclear translocation of p65. Moreover, a reporter gene assay using AP-1 specific luciferase reporter revealed that the enhanced activity of AP-1 by LPS was completely abolished in cells treated with purpureaside A. These results demonstrated that purpureaside A inhibited LPS-inducible iNOS expression in macrophages through the suppression of AP-1, but not of NF-kappaB.

Matrix metalloproteinase-1 inhibitor from the stem bark of Styrax japonica S. et Z.

A bioassay-guided fractionation of the ethyl acetate soluble fraction from the stem bark of Styrax japonica S. et Z. (Styracaceae) yielded two new lignan compounds, styraxjaponoside A (1) and styraxjaponoside B (2), along with three known compounds, matairesinoside (3), egonol glucoside (4), and dihydrodehydrodiconiferyl alcohol 9'-O-glucoside (5). The structures of compounds 1-5 were determined by spectroscopic method, as well as 1D- and 2D-NMR (HSQC, 1H-1H COSY, and HMBC) spectroscopy. Among them, compound 2 exhibited potent inhibitory activity against matrix metalloproteinase (MMP)-1, and prevented the UV-induced changes in the MMP-1 expression. In addition, compounds 3 and 5 were isolated from this plant for the first time.

Structure-antiviral activity relationships of cecropin A-magainin 2 hybrid peptide and its analogues.

In order to elucidate the structure-antiviral activity relationship of cecropin A (1-8)-magainin 2 (1-12) (termed CA-MA) hybrid peptide, several analogues with amino acid substitutions were synthesized. In a previous study, it was shown that serine at position 16 in CA-MA hybrid peptide was very important for antimicrobial activity. Analogues were designed to increase the hydrophobic property by substituting a hydrophobic amino acid residue (S --> A, V, F or W, position 16) in the CA-MA hybrid peptide. In this study, the structure-antiviral activity relationships of CA-MA and its analogues were investigated. In particular, substitution of Ser with a hydrophobic amino acid, Val, Phe or Trp at position 16 caused a dramatic increase in the virus-cell fusion inhibitory activity. These results suggested that the hydrophobicity at position 16 in the hydrophobic region of CA-MA is important for potent antiviral activity.

Pentacyclic triterpenoids and their cytotoxicity from the stem bark of Styrax japonica S. et Z.

The methylene chloride soluble fraction of MeOH extract from the stem bark of Styrax japonica S. et Z. (Styracaceae) showed significant cytotoxicity by SRB method against five human tumor cell lines. Four known pentacyclic triterpenoids, oleanolic aldehyde acetate (1), erythrodiol-3-acetate (2), euphorginol (3), and anhydrosophoradiol-3-acetate (4) were isolated by activity-guided fractionation. Their structures were determined by chemical and spectral analysis. Compounds 1-4 were isolated from S. japonica for the first time.

Antioxidative constituents from Buddleia officinalis.

Four flavonoids (1-4), a phenylethyl glycoside (5), and a phenylpropanoid glycoside (6) were isolated from the flowers of Buddleia officinalis (Loganiaceae). Their structures were determined by chemical and spectral analysis. Among the isolated compounds, luteolin (1) and acteoside (6) exhibited the most potent antioxidative activity on the NBT superoxide scavenging assay. In addition, compounds 1-6 revealed weak antifungal activity, and no hemolytic activity.

A new phenolic amide from Lycium chinense Miller.

A new phenolic amide, dihydro-N-caffeoyltyramine (1) was isolated from the root bark of Lycium chinense Miller, along with known compounds, trans-N-caffeoyltyramine (2), cis-N-caffeoyltyramine (3), and lyoniresinol 3alpha-O-beta-D-glucopyranoside (4). Their structures were determined by spectroscopic analysis. A NBT superoxide scavenging assay revealed that three phenolic amides showed potent antioxidative activity.