Black soybean promotes the formation of active components with antihepatoma activity in the fermentation product of Agaricus blazei

The antihepatoma activity and related active components in the fermentation products of Agaricus blazei (AB) cultured in the medium containing soybean (S) or black soybean (BS) were investigated. AB(BS)-pE and AB(S)-pE were the ethanolic extracts from the fermentation products of AB(BS) and AB(S), respectively. According to the IC 50 values, AB(BS)-pE (161.1 and 24.0 microg/mL for Hep 3B and Hep G2 cells, respectively) exhibited stronger cytotoxicities against hepatoma cells than AB(S)-pE (>200 and 99.9 microg/mL for Hep 3B and Hep G2 cells, respectively). AB(BS)-pE was separated by silica gel column chromatography and eluted with n-hexane/ethyl acetate/methanol gradient solvent system into 21 fractions. Fraction 3 [AB(BS)-pE-F3], eluted with n-hexane/ethyl acetate (97:3 and 19:1, v/v), was the most active fraction having inhibitory activity on the proliferation of Hep 3B and Hep G2 cells (IC 50 of 3.6 and 1.9 microg/mL, respectively). Three major compounds, compounds 1- 3, were further isolated from the AB(BS)-pE-F3 fraction by reversed-phase semipreparative high-performance liquid chromatography. Compounds 2 and 3 gave better antihepatoma activity than that of compound 1. The IC 50 values of compounds 2 and 3 were 2.8 and 4.5 microg/mL for Hep 3B cells and 1.4 and 2.0 microg/mL for Hep G2 cells, respectively. The structures of compounds 2 and 3 were identified by UV, IR, electron impact mass spectrometry, and (1)H and (13)C NMR to be blazeispirols A and C, respectively. Blazeispirols A and C existed in the mycelia but not in the broth and were more in AB(BS)-pE (49.9 +/- 8.9 and 14.2 +/- 2.4 mg/g, respectively) than AB(S)-pE (15.9 +/- 1.7 and 3.9 +/- 0.6 mg/g, respectively). Additionally, the result shows that the production of blazeispirols A and C was increased after cultivation in the medium containing black soybean on day 6 and reached the maximum on day 12, and the contents of blazeispirols A and C were negatively correlated with Hep 3B and Hep G2 cell viabilities ( r = -0.84 to -0.93, P < 0.01). It suggests that blazeispirols A and C could be used as biomarkers to produce the fermentation product of A. blazei with antihepatoma activity.     

Tumor cell proliferation and cyclooxygenase inhibitory constituents in horseradish (Armoracia rusticana) and Wasabi (Wasabia japonica)

Cyclooxygenase and human tumor cell growth inhibitory extracts of horseradish (Armoracia rusticana) and wasabi (Wasabia japonica) rhizomes upon purification yielded active compounds 1-3 from horseradish and 4 and 5 from wasabi rhizomes. Spectroscopic analyses confirmed the identities of these active compounds as plastoquinone-9 (1), 6-O-acyl-beta-d-glucosyl-beta-sitosterol (2), 1,2-dilinolenoyl-3-galactosylglycerol (3), linolenoyloleoyl-3-beta-galactosylglycerol (4), and 1,2-dipalmitoyl-3-beta-galactosylglycerol (5). 3-Acyl-sitosterols, sinigrin, gluconasturtiin, and phosphatidylcholines isolated from horseradish and alpha-tocopherol and ubiquinone-10 from wasabi rhizomes isolated were inactive in our assays. At a concentration of 60 microg/mL, compounds 1 and 2 selectively inhibited COX-1 enzyme by 28 and 32%, respectively. Compounds 3, 4, and 5 gave 75, 42, and 47% inhibition of COX-1 enzyme, respectively, at a concentration of 250 microg/mL. In a dose response study, compound 3 inhibited the proliferation of colon cancer cells (HCT-116) by 21.9, 42.9, 51.2, and 68.4% and lung cancer cells (NCI-H460) by 30, 39, 44, and 71% at concentrations of 7.5, 15, 30, and 60 microg/mL, respectively. At a concentration of 60 microg/mL, compound 4 inhibited the growth of colon, lung, and stomach cancer cells by 28, 17, and 44%, respectively. This is the first report of the COX-1 enzyme and cancer cell growth inhibitory monogalactosyl diacylglycerides from wasabi and horseradish rhizomes.     

Anti-inflammatory activities of new succinic and maleic derivatives from the fruiting body of Antrodia camphorata

Six new compounds, trans-3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]pyrrolidine-2,5-dione (1), trans-1-hydroxy-3-(4-hydroxyphenyl)-4-isobutylpyrrolidine-2,5-dione (2), cis-3-(4-hydroxyphenyl)-4-isobutyldihydrofuran-2,5-dione (3), 3-(4-hydroxyphenyl)-4-isobutyl-1H-pyrrole-2,5-dione (4), 3-(4-hydroxyphenyl)-4-isobutylfuran-2,5-dione (5), and dimethyl 2-(4-hydroxyphenyl)-3-isobutylmaleate (6), together with one known compound, 3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]furan-2,5-dione (7), were isolated from the fruiting bodies of Antrodia camphorata. The structures of the compounds were elucidated by analysis of their spectroscopic data. To investigate the immunomodulatory potential of the compounds, RAW264.7 macrophage cells were treated with the compounds. Compound 1 significantly increased spontaneous TNF-alpha secretion from unstimulated RAW264.7 cells but suppressed IL-6 production [50% inhibition concentration value (IC50) = 10 microg/mL] in LPS-stimulated cells. Compounds 3, 4, and 6 also suppressed IL-6 production with IC50 values of 17, 18, and 25 microg/mL, respectively, suggesting that these four compounds may have an anti-inflammatory effect on macrophage-mediated responses. Of the six compounds, compound 1 was the most effective, exerting both immunostimulatory and anti-inflammatory effects.     

Impact of alkyl esters of caffeic and ferulic acids on tumor cell proliferation, cyclooxygenase enzyme, and lipid peroxidation

The antioxidant ferulic and caffeic acid phenolics are ubiquitous in plants and abundant in fruits and vegetables. We have synthesized a series of ferulic and caffeic acid esters and tested for tumor cell proliferation, cyclooxygenase enzymes (COX-1 and -2) and lipid peroxidation inhibitory activities in vitro. In the tumor cell proliferation assay, some of these esters showed excellent growth inhibition of colon cancer cells. Among the phenolics esters assayed, compounds 10 (C12-caffeate), 11 (C16-caffeate), 21 (C8-ferulate), and 23 (C12-ferulate) showed strong growth inhibition with IC50 values of 16.55, 13.46, 18.67, and 7.57 microg/mL in a breast cancer cell line; 9.65, 7.45, 17.05, and 4.35 microg/ mL in a lung cancer cell line; 5.78, 3.5, 4.29, and 2.46 microg/mL in a colon cancer cell line; 12.04, 12.21, 14.63, and 8.09 microg/ mL in a central nervous system cancer cell line; and 8.62, 7.76, 11.0, and 5.37 in a gastric cancer cell line. In COX enzyme inhibitory assays, ferulic and caffeic acid esters significantly inhibited both COX-1 and COX-2 enzymes. Caffeates 5-10 (C4-C12), inhibited COX-1 enzyme between 50% and 90% and COX-2 enzyme by about 70%, whereas ferulates 15-21 (C3-C8) inhibited COX-1 and COX-2 enzymes by 85-95% 25 microg/mL. Long-chain caffeates 11-14 (C16-C22) and short-chain ferulates 15-20 (C3-C5) were the most active in lipid peroxidation inhibition and showed 60-70% activity at 5 microg/mL concentration.     

Effects of commercial anthocyanin-rich extracts on colonic cancer and nontumorigenic colonic cell growth

Commercially prepared grape (Vitis vinifera), bilberry (Vaccinium myrtillus L.), and chokeberry (Aronia meloncarpa E.) anthocyanin-rich extracts (AREs) were investigated for their potential chemopreventive activity against colon cancer. The growth of colon-cancer-derived HT-29 and nontumorigenic colonic NCM460 cells exposed to semipurified AREs (10-75 microg of monomeric anthocyanin/mL) was monitored for up to 72 h using a sulforhodamine B assay. All extracts inhibited the growth of HT-29 cells, with chokeberry ARE being the most potent inhibitor. HT-29 cell growth was inhibited approximately 50% after 48 h of exposure to 25 microg/mL chokeberry ARE. Most importantly, the growth of NCM460 cells was not inhibited at lower concentrations of all three AREs, illustrating greater growth inhibition of colon cancer, as compared to nontumorigenic colon cells. Extracts were semipurified and characterized by high-pressure liquid chromatography, spectrophotometry, and colorimetry. Grape anthocyanins were the glucosylated derivatives of five different anthocyanidin molecules, with or without p-coumaric acid acylation. Bilberry contained five different anthocyanidins glycosylated with galactose, glucose, and arabinose. Chokeberry anthocyanins were cyanidin derivatives, monoglycosylated mostly with galactose and arabinose. The varying compositions and degrees of growth inhibition suggest that the anthocyanin chemical structure may play an important role in the growth inhibitory activity of commercially available AREs.     

Synthesis, fungicidal, and insecticidal activities of beta-Methoxyacrylate-containing N-acetyl pyrazoline derivatives

1-Acetyl-3,-5-diarylpyrazolines have received considerable interests from the fields of medicinal and agricultural chemistry due to their broad spectrum of biological activities. To discover new lead compounds exhibiting both fungicidal and insecticidal activities, a series of pyrazoline derivatives were designed and synthesized by introducing the beta-methoxyacrylate pharmacophore into the scaffold of 1-acetyl-3,5-diarylpyrazoline. The fungicidal activities against Pseudoperoniospora cubensis, Sphaerotheca fuliginea, Botrytis cinerea, and Rhizoctonia solani and the insecticidal activities against Aphis medicagini, Nilaparvata legen, Mythima separata, and Tetranychus cinnabarnus were screened. The most potent compound 13, 1-aceto-3-[m-[o-(E-1-methoxycarboxyl-2-methoxy)-1-yl]benzyloxy]phenyl-5-(benzo-[1,3]-dioxolyl)-4,5-dihydro- pyrazoline, was identified. Its fungicidal IC(50) values against P. cubensis and S. fuliginea are 26.6 and 57.6 microg mL(-1), respectively, while its insecticidal LC(50) value against M. separata is 26.6 microg mL(-1). These results indicated that compound 13 could be used as a lead for further developing new pyrazoline type products exhibiting both fungicidal and insecticidal activities.     

Effect of yerba mate (Ilex paraguariensis) tea on topoisomerase inhibition and oral carcinoma cell proliferation

Tea flavonoids have antitopoisomerase activity and can inhibit cell proliferation. The objectives of this study were to determine the phenolic content of yerba mate tea products (MT) (Ilex paraguariensis) and evaluate their capacity to inhibit topoisomerase I (Topo I) and II (Topo II) activities and oral carcinoma cell proliferation. Total polyphenols of aqueous extracts of dried MT leaves were measured by the Folin-Ciocalteau assay, using chlorogenic (CH) and gallic (GA) acids as standards. Topoisomerase inhibition was determined by a clone-forming assay, which uses yeast (Saccharomyces cerevisiae) strains as a model. Controls included dimethyl sulfoxide (1.66%); camptothecin (50 microg/mL), a Topo I inhibitor; and amsacrine (100 microg/mL), a Topo II inhibitor. Cytotoxicity studies were conducted using a nontumorigenic human keratinocyte cell line HaCaT and two human squamous cancer cell lines (SCC-61 and OSCC-3). MT was found to be a rich source of phenolic compounds. Total polyphenol content of various commercially available traditional MT products ranged from 236 to 490 mg equiv of CH/g of dry leaves. Such levels were significantly different among products depending on their origin (P < 0.001). Higher anti-topoisomerase II activity was observed against JN394t(2-4) strain for Nobleza Gaucha MT (IC50 = 0.43 microg equiv of CH) in comparison to GA (IC50 = 112 mM) and CH (IC50 > 1500 mM). MT showed catalytic anti-topoisomerase activity against Topo II but not against Topo I. In addititon, MT exhibited dose-dependent cytotoxicity against all squamous cell lines tested. In comparison to premalignant cell line HaCaT [28 microg equiv of (+)-catechin mL(-1)], the cell line SCC-61 [21 microg equiv of (+)-catechin mL(-1)] was the most sensitive to MT, resulting in 50% inhibition of net cell growth. It is concluded that MT is rich in phenolic constituents and can also inhibit oral cancer proliferation. The effect on cancer cell proliferation may be mediated via inhibition of topoisomerase II. The lack of correlation between polyphenol content and the inhibition of topoisomerases suggests that the effect of MT on topoisomerase inhibition may be due to other still unidentified biologically active phytochemicals constituents.     

Biologically active carbazole alkaloids from Murraya koenigii

The bioassay guided fractionation of the acetone extract of the fresh leaves of Murraya koenigii resulted in the isolation of three bioactive carbazole alkaloids, mahanimbine (1), murrayanol (2), and mahanine (3), as confirmed from their (1)H and (13)C NMR spectral data. Compound 2 showed an IC(50) of 109 microg/mL against hPGHS-1 and an IC(50) of 218 microg/mL against hPGHS-2 in antiinflammatory assays, while compound 1 displayed antioxidant activity at 33.1 microg/mL. All three compounds were mosquitocidal and antimicrobial and exhibited topoisomerase I and II inhibition activities.     

In vitro anti-inflammatory and anti-proliferative activity of sulfolipids from the red alga Porphyridium cruentum

A sulfoglycolipidic fraction (SF) isolated from the red microalga Porphyridium cruentum was analyzed for fatty acid composition and assayed for ability to inhibit, in vitro, the generation of superoxide anion in primed leucocytes and the proliferation of a panel of human cancer cell-lines. Results demonstrated that SF contained large amounts of palmitic acid (26.1%), arachidonic acid (C20: 4 omega-6, 36.8%), and eicopentaenoic (C20:5 omega-3, 16.6%) acids, and noticeable amounts of 16:1n-9 fatty acid (10.5%). It strongly inhibited both the production of superoxide anion generated by peritoneal leukocytes primed with phorbol myristate acetate (IC(50): 29.5 microg/mL), and the growth of human colon adenocarcinoma DLD-1 and to a lesser extent of human breast adenocarcinoma MCF-7, human prostate adenocarcinoma PC-3, and human malignant melanoma M4 Beu cell-lines, and therefore might have a chemopreventive or chemotherapeutic potential, or both. It was found markedly more cytotoxic than sulfoquinovosyldiacylglycerols from plant used as a standard (STD), due to a stronger ability to inhibit DNA alpha-polymerase (IC(50): 378 microg/mL, vs 1784 microg/mL for STD). After a 48-h continuous treatment, IC(50) values for growth inhibition were in the range of 20-46 microg/mL instead of 94 to >250 microg/mL for STD, and those for inhibition of metabolic activity were in the range of 34-87 microg/mL instead of >250 microg/mL for STD. The higher anti-proliferative effect was observed on colon adenocarcinoma DLD-1 cells, and the weaker effect was observed on breast adenocarcinoma MCF-7.     

Isolation and identification of phase II enzyme-inducing agents from nonpolar extracts of green onion (Allium spp.)

The objective of the study was to isolate and identify potential cancer preventive constituents from green onion based on the ability to induce quinone reductase (QR, a representative phase II enzyme) in murine hepatoma cells (Hepa 1c1c7). Crude nonpolar solvent extracts were prepared from freeze-dried green onion by sequential refluxing with hexane and then ethyl acetate, followed by liquid-liquid extraction. Active fractions were subjected to the Hepa 1c1c7 bioassay-guided steps of flash chromatography, thin layer chromatography (TLC), and high-pressure preparative liquid chromatography (HPLC) to afford pure isolates capable of inducing QR. Multiple fractions were active in inducing QR. Five pure compounds were isolated from active fractions and identified using spectroscopic methods; these were p-hydroxyphenethyl trans-ferulate (1), 5,6-dimethyl-2-pyridinecarboxylic acid (2), ferulic acid (3), 1-(6-hydroxy-[3]pyridyl)-propan-1-one (4), and N-trans-feruloyl 3-O-methyldopamine (5). p-Hydroxyphenethyl trans-ferulate (1) doubled QR specific activity in Hepa 1c1c7 cells at a level of 2.1 microg/mL (6.6 microM).     

Study of anticancer activities of muscadine grape phenolics in vitro

Muscadine grapes have unique aroma and flavor characteristics. Although a few studies reported high polyphenols content of muscadine grapes, little research has been conducted to evaluate the phenolic compounds bioactivities in any muscadine grape cultivar. The objective of this study was to evaluate the effect of phenolic compounds in muscadine grapes on cancer cell viability and apoptosis. Four cultivars of muscadine (Carlos, Ison, Noble, and Supreme) were assessed in this study. Phenolic compounds were extracted from muscadine skins and further separated into phenolic acids, tannins, flavonols, and anthocyanins using HLB cartridge and LH20 column. Some individual phenolic acids and flavonoids were identified by HPLC. Anthocyanin fractions were more than 90% pure. The effect of different fractions on the viability and apoptosis of two colon cancer cell lines (HT-29 and Caco-2) was evaluated. A 50% inhibition of cancer cell population growth for the two cell lines was observed at concentrations of 1-7 mg/mL for crude extracts. The phenolic acid fractions showed a 50% inhibition at the level of 0.5-3 mg/mL. The greatest inhibitory activity was found in the anthocyanin fraction, with a 50% inhibition at concentrations of approximately 200 microg/mL in HT-29 and 100-300 microg/mL in Caco-2. Anthocyanin fractions also resulted in 2-4 times increase in DNA fragmentation, indicating the induction of apoptosis. These findings suggest that polyphenols from muscadine grapes may have anticancer properties.     

Synthesis and herbicidal activity of N,N-diethyl-3-(arylselenonyl)-1H-1,2,4-triazole-1-carboxamide

Based on the carbamoyl triazole herbicide Cafenstrole, 12 novel selenium-containing compounds were designed and synthesized. All of the compounds were characterized and confirmed by IR, 1H NMR, and high-resolution mass spectroscopy. The bioassay tests showed that some of the compounds (C2, C4, C(7-8), and C12) exhibited good inhibitory activity against cucumber (Cucumis sativus L.) and semen euphorbiae (Leptochloa chinensis N.). Especially, compound C6 inhibited the growth of cucumber and semen euphorbiae by >90% at a concentration of 1.875 microg/mL, and the inhibition of the compound on the rice (Oryza sativa L.) was only 8.3% at a concentration of 7.5 microg/mL, which indicated a higher selectivity between weed and rice than that shown by Cafenstrole.     

o-Orsellinaldehyde from the submerged culture of the edible mushroom Grifola frondosa exhibits selective cytotoxic effect against Hep 3B cells through apoptosis

The tumoricidal activity of a bioactive metabolite produced by submerged culture in a 2.1-L airlift fermentor of Grifola frondosa NTUS was investigated. After 14 days of cultivation, ethyl acetate extracts from the supernatant of culture broth (EES) were analyzed by cell viability assay. The IC50 of EES for cytotoxicity against human carcinoma cells (Hep 3B, Hep G2, HeLa, CL1-1) and normal human lung fibroblast MRC-5 was 78.4, 52.7, 77.6, 71.0, and 233.3 microg/mL, respectively. EES was further fractionated and a main cytotoxic compound, HE-5-5, was obtained. The IC50 of HE-5-5 based on the cell viability of Hep 3B and MRC-5 cells was 3.6 and 33.1 microg/mL, respectively. Thus, HE-5-5 showed a selective cytotoxic effect against Hep 3B cells and MRC-5. According to the UV, MS, and NMR data, HE-5-5 was identified as o-orsellinaldehyde. A DNA fragmentation assay together with the presence of a significant sub-G1 peak by flow cytometry suggested that o-orsellinaldehyde might mediate its cytotoxicity through apoptosis.     

Curcuma longa L. constituents inhibit sortase A and Staphylococcus aureus cell adhesion to fibronectin

The inhibitory activity of Curcuma longa L. (turmeric) rhizome constituents against sortase A, a bacterial surface protein anchoring transpeptidase, from Staphylococcus aureus ATCC 6538p was evaluated. The activity of the isolated compounds (1-4) was compared to that of the positive control,p-hydroxymecuribenzoic acid (pHMB). The biologically active components of C. longa rhizome were characterized by spectroscopic analysis as the curcuminoids curcumin (1), demethoxycurcumin (2), and bisdemethoxycurcumin (3). Curcumin was a potent inhibitor of sortase A, with an IC50 value of 13.8 +/- 0.7 microg/mL. Bisdemethoxycurcumin (IC50 = 31.9 +/- 1.2 microg/mL) and demethoxycurcumin (IC50 = 23.8 +/- 0.6 microg/mL) were more effective than pHMB (IC50 = 40.6 +/- 1.2 microg/mL). The three isolated compounds (1-3) showed no growth inhibitory activity against S. aureus strain Newman, with minimum inhibitory concentrations (MICs) greater than 200 microg/mL. Curcumin also exhibited potent inhibitory activity against S. aureus cell adhesion to fibronectin. The suppression of fibronectin-binding activity by curcumin highlights its potential for the treatment of S. aureus infections via inhibition of sortase activity. These results indicate that curcumin is a possible candidate in the development of a bacterial sortase A inhibitor.     

Moscatilin from Dendrobium nobile, a naturally occurring bibenzyl compound with potential antimutagenic activity.

A bibenzyl compound that possesses antimutagenic activity was isolated from the storage stem of Dendrobium nobile. The isolated compound suppressed the expression of the umu gene following the induction of SOS response in Salmonella typhimurium TA1535/pSK1002 that have been treated with various mutagens. The suppressive compound was mainly localized in the n-hexane extract fraction of the processed D. nobile. This n-hexane fraction was further fractionated by silica gel column chromatography, which resulted in the purification and subsequent identification of the suppressive compound. EI-MS and (1)H and (13)C NMR spectroscopy were then used to delineate the structure of the compound that confers the observed antimutagenic activity. Comparison of the obtained spectrum with that found in the literature indicated that moscatilin is the secondary suppressive compound. When using 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide) as the mutagen, moscatilin suppressed 85% of the umu gene expression compared to the controls at <0.73 micromol/mL, with an ID(50) value of 0.41 micromol/mL. Additionally, moscatilin was tested for its ability to suppress the mutagenic activity of other well-known mutagens such as 4-nitroquinoline-1-oxide (4NQO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), UV irradiation, 3-amino-1,4-dimethyl-5H-pyrido[4,3b]indole (Trp-P-1), benzo[a]pyrene (B[a]P), and aflatoxin B(1) (AFB(1)). With all of the aforementioned chemicals or treatments, moscatilin showed a dramatic reduction in their mutagenic potential. Interestingly, moscatilin almost completely suppressed (97%) the AFB(1)-induced SOS response at concentrations <0.73 micromol/mL, with an ID(50) of 0.08 micromol/mL. Finally, the antimutagenic activities of moscatilin against furylfuramide and Trp-P-1 were assayed by the Ames test using the S. typhimurium TA100 strain. The results those experiments indicated that moscatilin demonstrated a dramatic suppression of the mutagenicity of only Trp-P-1 but not furylfuramide.     

Total cranberry extract versus its phytochemical constituents: antiproliferative and synergistic effects against human tumor cell lines

Cranberries (Vaccinium macrocarpon Ait.) are an excellent dietary source of phytochemicals that include flavonol glycosides, anthocyanins, proanthocyanidins (condensed tannins), and organic and phenolic acids. Using C-18 and Sephadex Lipophilic LH-20 column chromatography, HPLC, and tandem LC-ES/MS, the total cranberry extract (TCE) has been analyzed, quantified, and separated into fractions enriched in sugars, organic acids, total polyphenols, proanthocyanidins, and anthocyanins (39.4, 30.0, 10.6, 5.5, and 1.2% composition, respectively). Using a luminescent ATP cell viability assay, the antiproliferative effects of TCE (200 microg/mL) versus all fractions were evaluated against human oral (KB, CAL27), colon (HT-29, HCT116, SW480, SW620), and prostate (RWPE-1, RWPE-2, 22Rv1) cancer cell lines. The total polyphenol fraction was the most active fraction against all cell lines with 96.1 and 95% inhibition of KB and CAL27 oral cancer cells, respectively. For the colon cancer cells, the antiproliferative activity of this fraction was greater against HCT116 (92.1%) than against HT-29 (61.1%), SW480 (60%), and SW620 (63%). TCE and all fractions showed >/=50% antiproliferative activity against prostate cancer cells with total polyphenols being the most active fraction (RWPE-1, 95%; RWPE-2, 95%; 22Rv1, 99.6%). Cranberry sugars (78.8 microg/mL) did not inhibit the proliferation of any cancer cell lines. The enhanced antiproliferative activity of total polyphenols compared to TCE and its individual phytochemicals suggests synergistic or additive antiproliferative interactions of the anthocyanins, proanthocyanidins, and flavonol glycosides within the cranberry extract.     

Isolation and identification of strawberry phenolics with antioxidant and human cancer cell antiproliferative properties

Studies suggest that consumption of berry fruits, including strawberries ( Fragaria x ananassa Duch.), may have beneficial effects against oxidative stress mediated diseases such as cancer. Berries contain multiple phenolic compounds, which are thought to contribute to their biological properties. Comprehensive profiling of phenolics from strawberries was previously reported using high-performance liquid chromatography with mass spectrometry (HPLC-MS) detection. The current study reports the isolation and structural characterization of 10 phenolic compounds from strawberry extracts using a combination of Amberlite XAD16-resin and C18 columns, HPLC-UV, and nuclear magnetic resonance (NMR) spectroscopy methods. The phenolics were cyanidin-3-glucoside ( 1), pelargonidin (2), pelargonidin-3-glucoside (3), pelargonidin-3-rutinoside (4), kaempferol (5), quercetin (6), kaempferol-3-(6'-coumaroyl)glucoside) (7), 3,4,5-trihydroxyphenyl-acrylic acid (8), glucose ester of ( E)- p-coumaric acid (9), and ellagic acid . Strawberry crude extracts and purified compounds 1- 10 were evaluated for antioxidant and human cancer cell antiproliferative activities by the Trolox equivalent antioxidant capacity (TEAC) and luminescent ATP cell viability assays, respectively. Among the pure compounds, the anthocyanins 1 (7156 microM Trolox/mg), 2 (4922 microM Trolox/mg), and 4 (5514 microM Trolox/mg) were the most potent antioxidants. Crude extracts (250 microg/mL) and pure compounds (100 microg/mL) inhibited the growth of human oral (CAL-27, KB), colon (HT29, HCT-116), and prostate (LNCaP, DU145) cancer cells with different sensitivities observed between cell lines. This study adds to the growing body of data supporting the bioactivities of berry fruit phenolics and their potential impact on human health.     

Green-leaf-derived C6-aroma compounds with potent antibacterial action that act on both Gram-negative and Gram-positive bacteria

All eight C6-aliphatic alcohol and aldehyde compounds in naturally occurring green leaves showed bacteriostatic effects against Staphylococcus aureus IFO 12732, methicillin-resistant S. aureus, Escherichia coli IFO 3301, E. coli O157:H7, and Salmonella enteritidis, with bacteriostatic activities of less than 12.5 microg mL(-1). In this study, the susceptibility of Gram-positive bacteria tested was observed to be greater than that of Gram-negative bacteria. The bactericidal action of the aldehyde compounds was found to be much stronger than that of the alcohol compounds under both liquid and gaseous conditions. The most effective compound was (3E)-hexenal at concentrations of 0.1 and 1 microg mL(-1), which killed 2.1 x 10(5) cfu mL(-1) of S. aureus IFO 12732 and 1.4 x 10(5) cfu mL(-1) of E. coli IFO 3301, respectively, by direct contact with the compound. Lethality of (3E)-hexenal against S. aureus IFO 12732 and E. coli IFO 3301 was also observed as a result of gaseous contact at concentrations of 3 and 30 microg mL(-1), respectively. The bactericidal effects of 30 microg mL(-1) (3E)-hexenal were thoroughly maintained throughout periods of 2 days and 1 day against S. aureus IFO 12732 and E. coli IFO 3301, respectively, by a complex formation with alpha-cyclodextrin.     

Structure-activity relationships of derivatives of fusapyrone, an antifungal metabolite of Fusarium semitectum

Fusapyrone (1) and deoxyfusapyrone (2) are two 3-substituted-4-hydroxy-6-alkyl-2-pyrones isolated from Fusarium semitectum that have considerable antifungal activity against molds. Because of their low zootoxicity and selective action they are potentially utilizable along with biocontrol yeasts for control of postharvest crop diseases. Seven derivatives of 1 (3 and 5-10) and one derivative of 2 (4) were obtained by chemical modifications of the glycosyl residue, the 2-pyrone ring, the aliphatic chain, or a combination thereof, and a structure-activity correlation study was carried out with regard to their zootoxicity and antifungal activity. Derivatives 7-10, as well as 1, were slightly zootoxic in Artemia salina (brine shrimp) bioassays, whereas pentaacetylation of 1 into 3, 5, and 6 resulted in a strong increase in toxicity. Compound 4, the tetraacetyl derivative of 2, was as toxic as 2. Because the structural changes of 1 that resulted in an increase of biological activity in A. salina bioassay were those that affected mainly the water solubility of the molecule, it appears that toxicity is related to hydrophobicity. Compounds 1 and 2 showed strong antifungal activity toward Botrytis cinerea, Aspergillus parasiticus, and Penicilliun brevi-compactum (minimum inhibitory concentration at 24 h = 0.78-6.25 microg/mL). Among derivatives 3-10, only compounds 7, 9, and 10 retained some activity, limited to B. cinerea and at high concentration (25-50 microg/mL). None of the compounds 1-10 inhibited the growth of the biocontrol yeasts Pichia guilliermondii and Rhodotorula glutinis at the highest concentration tested (50 microg/mL).     

Phenolic compounds from blueberries can inhibit colon cancer cell proliferation and induce apoptosis

Research has shown that diets rich in phenolic compounds may be associated with lower risks of several chronic diseases including cancer. This study systematically evaluated the bioactivities of phenolic compounds in rabbiteye blueberries and assessed their potential antiproliferation and apoptosis induction effects using two colon cancer cell lines, HT-29 and Caco-2. Polyphenols in three blueberry cultivars, Briteblue, Tifblue, and Powderblue, were extracted and freeze-dried. The extracts were further separated into phenolic acids, tannins, flavonols, and anthocyanins using an HLB cartridge and LH20 column. Some individual phenolic acids and flavonoids were identified by HPLC with >90% purity in anthocyanin fractions. The dried extracts and fractions were added to the cell culture medium to test for antiproliferation activities and induction of apoptosis. Flavonol and tannin fractions resulted in 50% inhibition of cell proliferation at concentrations of 70-100 and 50-100 microg/mL in HT-29 and Caco-2 cells, respectively. The phenolic acid fraction showed relatively lower bioactivities with 50% inhibition at approximately 1000 microg/mL. The greatest antiproliferation effect among all four fractions was from the anthocyanin fractions. Both HT-29 and Caco-2 cell growth was significantly inhibited by >50% by the anthocyanin fractions at concentrations of 15-50 microg/mL. Anthocyanin fractions also resulted in 2-7 times increases in DNA fragmentation, indicating the induction of apoptosis. The effective dosage levels are close to the reported range of anthocyanin concentrations in rat plasma. These findings suggest that blueberry intake may reduce colon cancer risk.