Anti-inflammatory activity of p-coumaryl alcohol-gamma-O-methyl ether is mediated through modulation of interferon-gamma production in Th cells.

BACKGROUND AND PURPOSE: p-Coumaryl alcohol-gamma-O-methyl ether (CAME) was isolated from Alpinia galanga and shown to contain a phenylpropanoid structure similar to p-coumaryl diacetate (CDA). CDA is known to have antioxidant and anti-inflammatory activity, but the biochemical activities of CAME are unknown. Inflammation is mediated by inflammatory cytokine production, in particular, by CD4+ T helper cells (Th cells), but it is unclear whether phenylpropanoids affect cytokine production in Th cells. In this study, we decided to investigate the functions of CAME and CDA in CD4+ Th cells. EXPERIMENTAL APPROACH: Mouse CD4+ Th cells were isolated from C57BL6 mice and stimulated with an antibody against T cell receptors in the presence of phenylpropanoids. Cytokine production was measured by elisa and intracellular cytokine staining. Gene knockout mice and tetracycline-inducible transgenic mice were used to examine the molecular mechanisms of phenylpropanoids on modulation of cytokine production. KEY RESULTS: CAME potently reduced intracellular reactive oxygen species in Th cells, as does CDA. However, although CDA was cytotoxic, CAME selectively and potently suppresses interferon-gamma (IFNgamma) production in CD4+ Th cells, without toxicity. This effect was caused by attenuated expression of the transcription factor, T-box protein expressed in T cells (T-bet), and T-bet was essential for CAME to inhibit IFNgamma production in CD4+ Th cells. CONCLUSIONS AND IMPLICATIONS: CAME selectively and substantially suppresses IFNgamma production in CD4+ Th cells by decreasing T-bet expression. As increased IFNgamma production by CD4+ Th cells can mediate inflammatory immune responses, a selective IFNgamma suppressor, such as CAME may be an effective, naturally occurring, compound for modulating inflammatory immune disorders.

Macharistol, a new cytotoxic cinnamylphenol from the stems of Machaerium aristulatum.

A new cinnamylphenol, macharistol (1), along with a known pterocarpan, (+)-medicarpin (2), were isolated as cytotoxic constituents from the stems of Machaerium aristulatum. In addition, a known pterocarpan, (+)-maackiain (3), and a known isoflavone, formononetin (4), were identified as inactive constituents. Compound 1 was evaluated in the in vivo hollow fiber assay with KB, Col-2, and hTERT-RPE1 cells and found to be inactive at the highest dose (25 mg/kg body weight) tested.

Cytotoxic constituents of Psoralea corylifolia.

A coumestan derivative, psoralidin (1) was found to be a cytotoxic principle of the seeds of Psoralea corylifolia L. (Leguminosae) with the IC50 values of 0.3 and 0.4 microg/ml against the HT-29 (colon) and MCF-7 (breast) human cancer cell lines, respectively. A coumarin, angelicin (2) was also isolated as a marginally cytotoxic agent along with an inactive compound, psoralen (3) from the plant. The isolates 1-3 were not active against the A541 (lung) and HepG2 (liver hepatoma) cancer cell lines.

Effect of dietary Platycodon grandiflorum on the improvement of insulin resistance in obese Zucker rats.

The effect of dietary Platycodon grandiflorum on the improvement of insulin resistance and lipid profile was investigated in lean (Fa/-) and obese (fa/fa) Zucker rats, a model for noninsulin dependent diabetes mellitus. Dietary Platycodon grandiflorum feeding for 4 weeks resulted in a significant decrease in the concentration of plasma triglyceride in both lean and obese Zucker rats. Furthermore, dietary Platycodon grandiflorum markedly decreased both plasma cholesterol and fasting plasma insulin levels, and significantly decreased the postprandial glucose level at 30 min during oral glucose tolerance test in obese Zucker rats. Although there was no statistical significance, the crude glucose transporter 4 protein level of obese rats fed Platycodon grandiflorum tended to increase when compared with that of obese control rats. Therefore, the present results suggested that dietary Platycodon grandiflorum may be useful in prevention and improvement of metabolic disorders characterized by hyperinsulinemia states such as noninsulin dependent diabetes mellitus, syndrome X, and coronary artery disease.

New bioactive aromatic compounds from Vismia guianensis.

Five benzophenones, vismiaguianones A-E, and two benzocoumarins, vismiaguianins A and B were isolated from the CHCl3 extract of the roots of Vismia guianensis by bioassay-directed fractionation using the DNA strand-scission assay and KB cell line. Of the isolates obtained, vismiaguianone B exhibited DNA strand-scission activity, whereas vismiaguianones D and E and vismiaguianin A were found to be significantly cytotoxic.

5-(4-Hydroxyphenethenyl)-4,7-dimethoxycoumarin, a new constituent of Monotes engleri.

A new coumarin, 5-(4-hydroxyphenethenyl)-4,7-dimethoxycoumarin (1) was isolated from the combined ethyl acetate extracts of the root bark, root wood and stem bark of Monotes engleri, and found to be cytotoxic against two cell lines in a human tumor panel. Its structure was determined on the basis of spectroscopic methods.

Immune-stimulating properties of polysaccharides from Phellodendri cortex (Hwangbek).

Heteropolysaccarides were isolated from the Korean medicinal plant, Phellodendri cortex (Hwangbek), by hot water and alkali extractions. The extracted polysaccharides were fractionated into eight fractions and they are mainly composed of D-N-acetylglucosamine, D-galactose, D-mannose, and D-glucose. Among the polysaccharide fractions, Fr.-2 showed a potent B-lymphocyte-stimulating activity in a system using polyclonal antibody forming cells in C57BL/6XC3H mice at dosages of 2-10 mg. On the basis of their solubility in aqueous ethanol, four fractions of Fr.-2-1 to Fr.-2-4 were further obtained from the Fr.-2, and Fr.-2-3 was divided into Fr.-2-3-1, 2, 3, and 4 by DEAE cellulose chromatography. The main activity was found in Fr.-2-3-2, which contained 100% (w/w) of carbohydrates and further purified to Fr.-2-3-2-2 by gel filtration chromatography using TSK Gel HW50S. Fr.-2-3-2-2, having a molecular weight of about 230 kDa, showed the highest B-cell-stimulating activity and the half-maximal concentration for B-lymphocyte-stimulating activity was ca. 2.2 microg/ml.

New biphenyl compounds with DNA strand-scission activity from Clusia paralicola.

Three new biphenyl derivatives, clusiparalicolines A (1), B (2), and C (3), were isolated from the roots of Clusia paralicola by bioassay-directed fractionation using the DNA strand-scission and the KB human cancer cell line cytotoxicity assays. Compounds 1 and 2 were found to be active in the DNA strand-scission assay, whereas all three compounds exhibited modest cytotoxicity against the KB cell line. The structures of 1-3 were elucidated by spectroscopic methods including 1D and 2D NMR techniques.

Cytotoxic constituents from the roots of Tovomita brevistaminea.

Two known xanthones, trapezifolixanthone and manglexanthone were isolated as cytotoxic constituents from the CHCl3 extract of the roots of Tovomita brevistaminea by bioassay-guided fractionation using the KB cell line. In addition, a new compound, tovophenone C, and two known compounds, tovophenones A and B which are benzophenones, were found to be inactive constituents in this investigation. The structure of the new isolate was determined by detailed analysis of spectroscopic parameters including its 1D and 2D NMR spectroscopy data.

New compounds with DNA strand-scission activity from the combined leaf and stem of Uvaria hamiltonii.

Two flavanones, hamiltones A (1) and B (2), an aurone, hamiltrone (3), a chalcone, hamilcone (4), and a tetrahydroxanthene, hamilxanthene (5), were isolated from Uvaria hamiltonii extracts guided initially by fractionation based on DNA strand-scission and/or 9KB cytotoxicity assays. Compounds 2-5 have not been reported previously, while 1 is new as a natural product. Structural assignments were made based on extensive spectroscopic measurements. Compounds 1-3 were inactive in the 9KB cytotoxicity assay, with compounds 4 and 5 having weak activity. In the DNA strand-scission assay, 3 was the most active compound found in the DNA strand-scission assay, being 10 times more potent than 1 or 2. Compound 4 was only weakly active, and 5 was inactive.

Cytotoxic prenylated flavanones from Monotes engleri.

From the leaves of Monotes engleri, five prenylated flavanones were isolated as constituents that displayed cytotoxic activity against several human cancer cell lines. There of these substances are novel, namely, 6-(1,1-dimethylallyl)naringenin, 6-(1,1-dimethylallyl)eriodictyol and 3'-O-methyl-6-(1,1-dimethylallyl)-eriodictyol, with the other two active substances being the known flavanones, 6,8-diprenyleriodictyol and hiravanone. Additionally, two novel, but non-cytotoxic, biogenetically related flavanones were isolated, 6-[(2RS)-hydroxy-3-methyl-3-butenyl]-8-prenyleriodictyol and 5,4'-dihydroxy-4",4"-dimethyl-5"-methyl-5"H-dihydrofurano[2",3": 6,7]flavanone. The structures of the new compounds were determined by spectral analysis 1D- and 2D-NMR experiments.