Polyphenolic and molecular variation in Thymus species using HPLC and SRAP analyses.

In the present research, inter and intra genetic variability of 77 accessions belonging to 11 Thymus species were assessed using eight SRAP primer combinations. High polymorphism (98.3%) was observed in the studied species. The cluster analysis classified Thymus species into five main groups. According to molecular variance (AMOVA) analysis, 63.14% of total genetic variation was obtained within the species, while 36.86% of variation was observed among species. STRUCTURE analysis was also performed to estimate the admixture of species. For instance, T. carmanicus and T. transcaspicus revealed high admixtures. HPLC analysis also demonstrated the presence of rosmarinic acid (32.3-150.7 mg/100 g DW), salvianolic acid (8-90 mg/100 g DW), and cinnamic acid (1.7-32.3 mg/100 g DW) as major phenolic acids, as well as apigenin, epicatechin, and naringenin as the major flavonoids. The highest phenolic and flavonoid contents were detected in T. transcaspicus (37.62 mg gallic acid equivalents (GAE) g-1 DW) and T. vulgaris (8.72 mg quercetin equivalents (QE) g-1 DW), respectively. The antioxidant properties and total phenolic of Thymus species were examined using DPPH and ß-carotene-linoleic acid model systems and consequently T. vulgaris and T. pubescens were detected with the highest and the lowest antioxidant activities respectively. Cluster and principal Components Analysis (PCA) of the components classified the species in to three groups. Finally, similarity within some species was observed comparing molecular and phytochemical markers. For instance, T. vulgaris separated from other species according to major polyphenolic profiles and molecular analyses, as well as T. transcaspicus, T. carmanicus, and T. fedtschenkoi that were clustered in the same groups.

Assessment of the Biological Activity and Phenolic Composition of Ethanol Extracts of Pomegranate (Punica granatum L.) Peels.

Pomegranate (Punica granatum L.) is a rich source of constituents with confirmed strong biological activities. However, pomegranate peel, which encompasses approximately 30-40% of its weight, is treated as a biological waste. The aim of this paper was to evaluate the potential of pomegranate peel extracts and to propose its functional properties that can be used for development of functional products. Eight ethanol extracts of pomegranate peels (PPEs) were characterized by use of direct infusion quadrupole-time of flight (Q-TOF), and afterwards tested on their antioxidant, antibacterial and antiproliferative activities. Mass spectrometry analysis revealed that the most prevalent compounds in pomegranate peels were punicalagin, granatin and their derivatives. Analysed extracts had high total phenolic contents that ranged from 5766.44 to 10599.43 mg GAE/100 g, and strong antioxidant activity (7551.31-7875.42 and 100.25-176.60 µmol TE/100 g for DPPH and FRAP assays, respectively). The results of biological activity assays showed that all PPEs possessed antibacterial activity, and that S. aureus was the most sensitive specie with minimum inhibitory concentration and minimum bactericidal concentrations ranging from 0.8 to 6.4 mg/mL. Additionally, the analysis of antiproliferative activity revealed high potency of PPEs, as the IC50 values ranged from 0.132 mg/mL to 0.396 mg/mL. Multivariate analysis pointed out the most discriminative metabolites for antioxidant or antiproliferative activity. Overall, the pomegranate peel confirmed to be a highly valuable source of bioactive compounds that could be used to improve the food functional characteristics.

Identification and accumulation of phenolic compounds in the leaves and bark of Salix alba (L.) and their biological potential.

The study examines the phenolic compounds in hydromethanolic extracts of Salix alba (L.) leaves and bark as well as their antioxidant activity and cytotoxic potential. UPLC-PDA-Q/TOF-MS analysis showed a total of 29 phenolic compounds in leaves and 34 in bark. Total phenolic compound content was 5575.96 mg/100 g of dry weight (DW) in leaves and 2330.31 mg/100 g DW in bark. The compounds were identified as derivatives of phenolic acids (seven in leaves and five in bark), flavanols and procyanidins (eight in leaves and 26 in bark) and flavonols (14 in leaves and three in bark). Both extracts exhibited strong antioxidant potential, assessed by radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), but the bark extract was even stronger than the ascorbic acid used as a standard. The cytotoxicity of both extracts was evaluated against human skin fibroblasts and human epidermal keratinocytes cell lines using the Presto Blue cell viability assay. The keratinocytes were more resistant to tested extracts than fibroblasts. The leaf and bark extracts at concentrations which exhibited antioxidant activity were also not toxic against the keratinocyte cell line. Thus, S. alba extracts, especially the leaf extract, offer promise as a nontoxic natural antioxidant, in cosmetic products or herbal medicines, and as a source of bioactive secondary metabolites.

Wine's Phenolic Compounds and Health: A Pythagorean View.

In support of the J curve that describes the association between wine consumption and all-cause mortality, researchers and the lay press often advocate the health benefits of (poly)phenol consumption via red wine intake and cite the vast amount of in vitro literature that would corroborate the hypothesis. Other researchers dismiss such evidence and call for total abstention. In this review, we take a skeptical, Pythagorean stance and we critically try to move the debate forward by pointing the readers to the many pitfalls of red wine (poly)phenol research, which we arbitrarily treat as if they were pharmacological agents. We conclude that, after 30 years of dedicated research and despite the considerable expenditure, we still lack solid, "pharmacological", human evidence to confirm wine (poly)phenols' biological actions. Future research will eventually clarify their activities and will back the current recommendations of responsibly drinking moderate amounts of wine with meals.

Comparison of Bioactive Phenolic Compounds and Antioxidant Activities of Different Parts of Taraxacum mongolicum.

Herbs derived from Taraxacum genus have been used as traditional medicines and food supplements in China for hundreds of years. Taraxacum mongolicum is a famous traditional Chinese medicine derived from Taraxacum genus for the treatment of inflammatory disorders and viral infectious diseases. In the present study, the bioactive phenolic chemical profiles and antioxidant activities of flowers, leaves, and roots of Taraxacum mongolicum were investigated. Firstly, a high performance liquid chromatography method combined with segmental monitoring strategy was employed to simultaneously determine six bioactive phenolic compounds in Taraxacum mongolicum samples. Moreover, multivariate statistical analysis, including hierarchical clustering analysis, principal component analysis, and partial least squares discriminant analysis were performed to compare and discriminate different parts of Taraxacum mongolicum based on the quantitative data. The results showed that three phenolic compounds, caftaric acid, caffeic acid, and luteolin, could be regarded as chemical markers for the differences of flowers, leaves, and roots of Taraxacum mongolicum. In parallel, total phenolic contents, total flavonoid contents and antioxidant activities of different parts of Taraxacum mongolicum were also evaluated and compared. It is clear that Taraxacum mongolicum had antioxidant properties, and the antioxidant capacities of different parts of Taraxacum mongolicum in three antioxidant assays showed a similar tendency: Flowers ≈ leaves > roots, which revealed a positive relationship with their total phenolic and flavonoid contents. Furthermore, to find the potential antioxidant components of Taraxacum mongolicum, the latent relationships of the six bioactive phenolic compounds and antioxidant activities of Taraxacum mongolicum were investigated by Pearson correlation analysis. The results indicated caftaric acid and caffeic acid could be the potential antioxidant ingredients of Taraxacum mongolicum. The present work may facilitate better understanding of differences of bioactive phenolic constituents and antioxidant activities of different parts of Taraxacum mongolicum and provide useful information for utilization of this herbal medicine.

Phenolic Profile, Antioxidant and Anti-Proliferative Activities of Methanolic Extracts from Asclepias linaria Cav. Leaves.

Asclepias linaria Cav. (Apocynaceae) is a shrubby plant endemic of Mexico which has been used in traditional medicine. However, the bioactive potential of this plant remains unexplored. In this study, the phenolic composition, antioxidant, and cytotoxic activities of A. linaria leaves were determined. In order to estimate the phenolic composition of the leaves, the total phenolic, flavonoid, and condensed tannins contents were determined. Furthermore, the antioxidant activity was measured by the scavenging activity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2'-azino-bis[3-ethylbenzothiazoline-6-sulphonic acid] (ABTS•+) radicals and the total antioxidant capacity. The phenolic compounds identified in the A. linaria leaves by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) include phenolic acids, such as p-coumaric and ferulic acid, as well as flavonoids, such as rutin and quercetin. The leaves' extracts of A. linaria showed a high scavenging activity of DPPH• and ABTS•+ radicals (IC50 0.12 ± 0.001 and 0.51 ± 0.003 µg/mL, respectively), high total antioxidant capacity values (99.77 ± 4.32 mg of ascorbic acid equivalents/g of dry tissue), and had a cytotoxic effect against K562 and HL60 hematologic neoplasia cells lines, but no toxicity towards the normal mononuclear cell line was observed. These results highlight the potential of A. linaria and could be considered as a possible alternative source of anticancer compounds.

Natural antioxidants of plant origin.

Interest in the content of natural antioxidants in plant-based foods can be from the human health perspective, in terms of how these compounds might help promote one's health and wellness, or from the storage point-of-view, as the endogenous antioxidant constituents aid to extend a foodstuff's shelf-life. This chapter reports essential information about the mechanism of antioxidant action and methods employed for determination of their activity, classes of phenolic compounds (phenolic acids, flavonoids, lignans, stilbenes, tannins), sources of plant antioxidants (oil seeds, cereals, legumes, plants of the Lamiaceae family, tea and coffee, tree nuts, fruits, and berries), extraction strategies of phenolic compounds from plant material, and the influence of processing and storage on the content of natural antioxidants in foods and their antioxidant activity. Thermal processing, if not releasing bound phenolics from the structural matrices of the food, tends to decrease the antioxidant potential or, in the best case scenario, has no significant negative impact. Gentler sterilization processes such as high-pressure processing tend to better retain the antioxidant potential of a foodstuff than thermal treatments such as steaming, boiling, or frying. The impact of processing can be assessed by determining the antioxidant potential of foodstuffs either at the point of formulation or after different periods of storage under specified conditions.

Solidago graminifolia L. Salisb. (Asteraceae) as a Valuable Source of Bioactive Polyphenols: HPLC Profile, In Vitro Antioxidant and Antimicrobial Potential.

Solidago species are often used in traditional medicine as anti-inflammatory, diuretic, wound-healing and antimicrobial agents. Still, the bioactive compounds and biological activities of some species have not been studied. The present work aimed to investigate the polyphenolic profile and the biological properties of Solidago graminifolia L. Salisb., a poorly explored medicinal plant. The hydroalcoholic extracts from aerial parts were evaluated for total phenolic content (TPC), total flavonoid content (TFC) and the polyphenolic compounds were investigated by HPLC-MS. The antioxidant potential in vitro was determined using DPPH and FRAP assays. Antibacterial and antifungal effects were evaluated by dilution assays and MIC, MBC and MFC were calculated. The results showed that Solidago graminifolia aerial parts contain an important amount of total phenolics (192.69 mg GAE/g) and flavonoids (151.41 mg RE/g), with chlorogenic acid and quercitrin as major constituents. The hydroalcoholic extracts showed promising antioxidant and antimicrobial potential, with potent antibacterial activity against Staphylococcus aureus and important antifungal effect against Candida albicans and C. parapsilosis. The obtained results indicated that the aerial parts of Solidago graminifolia could be used as novel resource of phytochemicals in herbal preparations with antioxidant and antimicrobial activities.

The Pharmacological Potential of Oil Palm Phenolics (OPP) Individual Components.

The oil palm tree (Elaeis guineensis) from the family Arecaceae is a high oil-producing agricultural crop. A significant amount of vegetation liquor is discarded during the palm oil milling process amounting to 90 million tons per year around the world. This water-soluble extract is rich in phenolic compounds known as Oil Palm Phenolics (OPP). Several phenolic acids including the three isomers of caffeoylshikimic acid (CFA), p-hydroxybenzoic acid (PHBA), protocatechuic acid (PCA) and hydroxytyrosol are among the primary active ingredients in the OPP. Previous investigations have reported several positive pharmacological potentials by OPP such as neuroprotective and atheroprotective effects, anti-tumor and reduction in Aß deposition in Alzheimer's disease model. In the current review, the pharmacological potential for CFA, PHBA, PCA and hydroxytyrosol is carefully reviewed and evaluated.

Quantificação de metabólitos secundários e avaliação da atividade antimicrobiana e antioxidante de algumas plantas selecionadas do Cerrado de Mato Grosso / Quantification of secondary metabolites and antimicrobial and antioxidant activities of some medicinal plants from the Cerrado of the Mato Grosso

RESUMO Extratos etanólicos de Luehea paniculata, Anadenanthera colubrina, Cariniana rubra, Hancornia speciosa, Qualea grandiflora, Kielmeyera coriaceae e Palicourea rigida, coletadas no Cerrado de Mato Grosso foram submetidos à análise fitoquímica preliminar para identificação das principais classes de metabolitos secundários e à quantificação do teor de compostos fenólicos totais, flavonoides e cumarinas. O estudo também descreve a atividade antimicrobiana, antioxidante e a toxicidade preliminar frente a larvas de Artemia salina. Os extratos de C. rubra e Q. grandiflora foram os mais ativos contra as cepas fúngicas de C. neoformans (CIM 3,91 µg/mL), C. krusei(CIM 15,63 µg/mL), C. parapsilosis (CIM 31,25 µg/mL) e C. albicans (CIM 62,5 µg/mL), ambos com os mesmos resultados para estes microrganismos. Em relação às cepas bacterianas a mais sensível foi S. aureus com CIM de 250 µg/mL para todos os extratos testados. Luhea paniculata e Q. grandiflora foram as espécies vegetais mais ativas contra E. coli (CIM 500 e 250 µg/mL, respectivamente) e E. faecalis (CIM 250 e 500 µg/mL, respectivamente). No teste do DPPH, merece destaque as espécies K. coriaceae (Ca) (IC50 = 0,72 ± 0,51 μg /mL), K. coriaceae (Fo) (IC50 = 1,34 ± 0,53 μg /mL), H. speciosa (Fo)(IC50 = 1,03 ± 0,52 μg /mL), Q. grandiflora (Fo) (IC50 = 1,31 ± 0,19 μg /mL) e P. rigida (Fo) (IC50 = 1,39 ± 0,53 μg /mL). Com exceção de L. paniculata(Fo), que apresentou IC50 de 14,40 ± 0,34 μg /mL e teor de flavonoides de 295,5 mg/g, todas as espécies que tiverem significativa atividade no teste do DPPH, também apresentaram teor de flavonoides semelhante ao padrão, ou seja, H. speciosa (Fo) (280,5 mg/g), Q. grandiflora(Fo) (260,5 mg/g), K. coriaceae (Ca) (250,5 mg/g), K. coriaceae (Fo) (235,5 mg/g). Quanto à determinação de fenóis totais e cumarinas os resultados foram inferiores quando comparados aos padrões.

ABSTRACT Ethanol extracts of Luehea paniculata, Anadenanthera colubrina, Cariniana rubra, Hancornia speciosa, Qualea grandiflora, Kielmeyera coriaceae and Palicourea rigida, collected in the Cerrado of Mato Grosso went through preliminary phytochemical analysis in order to identify major classes of secondary metabolites and also to quantify the total content of phenolics, flavonoids and coumarins. The study also describes the antimicrobial and antioxidant activity and the toxicity of the larva of Artemia salina. The C. rubra extracts and the Q. grandiflora were the most active against fungal strains of C. neoformans (MIC 3.91 µg/ml), C. krusei (MIC 15.63 µg/ml), C. parapsilosis(31.25 MIC µg/ml) and C. albicans (MIC 62.5 µg/ml), both with the same results for these organisms. Regarding the bacterial strains, the most sensitive one was the S. aureus with 250 µg/ml MIC for all the tested extracts. The Luhea paniculata and the Q. grandiflora were the most active against E. coli species (MIC 500 and 250 µg/ml, respectively) and E. faecalis (MIC 250 and 500 µg/ml, respectively). In the test of DPPH, K. coriaceae (Ca) (IC50 = 0.72 ± 0.51 µg/mL), K. coriaceae (Fo) (IC50 = 1.34 ± 0.53 µg/mL), H. speciosa (Fo) (IC50= 1.03 ± 0.52 µg/mL), Q. grandiflora (Fo) (IC50 = 1.31 ± 0.19 µg/ml) and P. rigida (Fo) (1.39 ± 0,53 µg/ml) stood out. With the exception of the L. paniculata (Fo), which showed an IC50 of 14.40 ± 0.34 µg/ml and a flavonoid content of 295.5 mg/g, all species that had significant activity in the DPPH test, also showed flavonoid content similar to the standard one, or H. speciosa (Fo) (280.5 mg/g) Q. grandiflora (Fo) (260.5 mg/g), K. coriaceae (Ca) (250.5 mg/g), K. coriaceae (Fo) (235.5 mg/g).

Effects-based chemical category approach for prioritization of low affinity estrogenic chemicals.

Regulatory agencies are charged with addressing the endocrine disrupting potential of large numbers of chemicals for which there is often little or no data on which to make decisions. Prioritizing the chemicals of greatest concern for further screening for potential hazard to humans and wildlife is an initial step in the process. This paper presents the collection of in vitro data using assays optimized to detect low affinity estrogen receptor (ER) binding chemicals and the use of that data to build effects-based chemical categories following QSAR approaches and principles pioneered by Gilman Veith and colleagues for application to environmental regulatory challenges. Effects-based chemical categories were built using these QSAR principles focused on the types of chemicals in the specific regulatory domain of concern, i.e. non-steroidal industrial chemicals, and based upon a mechanistic hypothesis of how these non-steroidal chemicals of seemingly dissimilar structure to 17ß-estradiol (E2) could interact with the ER via two distinct binding types. Chemicals were also tested to solubility thereby minimizing false negatives and providing confidence in determination of chemicals as inactive. The high-quality data collected in this manner were used to build an ER expert system for chemical prioritization described in a companion article in this journal.

Mutagenicity and DNA damage of bisphenol A and its structural analogues in HepG2 cells.

Environmental oestrogen bisphenol A (BPA) and its analogues are widespread in our living environment. Because their production and use are increasing, exposure of humans to bisphenols is becoming a significant issue. We evaluated the mutagenic and genotoxic potential of eight BPA structural analogues (BPF, BPAF, BPZ, BPS, DMBPA, DMBPS, BP-1, and BP-2) using the Ames and comet assay, respectively. None of the tested bisphenols showed a mutagenic effect in Salmonella typhimurium strains TA98 and TA100 in either the presence or absence of external S9-mediated metabolic activation (Aroclor 1254-induced male rat liver). Potential genotoxicity of bisphenols was determined in the human hepatoma cell line (HepG2) at non-cytotoxic concentrations (0.1 µmol L(-1) to 10 µmol L(-1)) after 4-hour and 24-hour exposure. In the comet assay, BPA and its analogue BPS induced significant DNA damage only after the 24-hour exposure, while analogues DMBPS, BP-1, and BP-2 induced a transient increase in DNA strand breaks.

Plant polyphenols and their anti-cariogenic properties: a review.

Polyphenols constitute one of the most common groups of substances in plants. Polyphenolic compounds have been reported to have a wide range of biological activities, many of which are related to their conventional antioxidant action; however, increasing scientific knowledge has highlighted their potential activity in preventing oral disease, including the prevention of tooth decay. The aim of this review is to show the emerging findings on the anti-cariogenic properties of polyphenols, which have been obtained from several in vitro studies investigating the effects of these bioactive molecules against Streptococcus mutans, as well as in vivo studies. The analysis of the literature supports the anti-bacterial role of polyphenols on cariogenic streptococci, suggesting (1) a direct effect against S. mutans; (2) an interaction with microbial membrane proteins inhibiting the adherence of bacterial cells to the tooth surface; and (3) the inhibition of glucosyl transferase and amylase. However, more studies, particularly in vivo and in situ, are necessary to establish conclusive evidence for the effectiveness and the clinical applications of these compounds in the prevention of dental caries. It is essential to better determine the nature and distribution of these compounds in our diet and to identify which of the hundreds of existing polyphenols are likely to provide the greatest effects.

Characterization of neurotoxic effects of NMDA and the novel neuroprotection by phytopolyphenols in mice.

Excitotoxicity plays a major role in various neurological disorders. In this study, we explored the behavioral and neurotoxic effects of intraventricular NMDA administration in mice. After NMDA injection, acute seizures were followed by impairments in locomotor activity, motor performance on a rotarod, and climbing ability. Mice killed 1 day after NMDA administration showed increased synaptosomal reactive oxygen species ROS production and calcium concentration and decreased mitochondrial membrane potential, mitochondrial reductase activities, and neuronal membrane Na+, K+ -ATPase and mg2+ -ATPase activities. One and 3 days after excitotoxic injury, Golgi stains showed that dendritic length and spine density were significantly decreased in neurons of the hippocampal dentate gyrus. Some mice received honokiol, tea polyphenol plus memantine, and honokiol plus memantine prior to NMDA treatment; the occurrence of generalized seizures was attenuated, seizure scores were reduced, latency to generalized seizures was prolonged, and motor impairments were lessened. Moreover, all of the neurochemical changes of the synaptosomes were also ameliorated. In conclusion, the behavioral and neurotoxic effects of intracerebroventricular injection of NMDA were ameliorated by treatment with honokiol alone or combined treatment with either tea polyphenol plus memantine or honokiol plus memantine, but only partly by either tea polyphenol or memantine alone. The therapeutic potential of these neuroprotective regimens in treating excitotoxicity-related diseases merits for further investigation.

Combining naturally occurring polyphenols with TNF-related apoptosis-inducing ligand: a promising approach to kill resistant cancer cells?

TNF-related apoptosis-inducing ligand (TRAIL) and its receptors are attractive targets for anticancer therapy owing to their ability to trigger apoptosis selectively in cancer cells but not in normal cells. To date, many combinatorial strategies, such as chemotherapy or radiotherapy, have given encouraging results for overcoming TRAIL resistance in preclinical models. In this review, we provide an overview of the molecular mechanisms underlying sensitization to TRAIL-induced apoptosis by polyphenols. These naturally occurring compounds can restore tumor cell sensitivity to TRAIL-induced cell death with no apparent toxicity towards normal cells. Both extrinsic and intrinsic pathways can be modulated by polyphenols, the activation of which largely depends on the cell type, the particular polyphenolic compound, and the conditions of treatment. The large variety of polyphenol cellular targets could prove useful in circumventing TRAIL resistance. The relevance of these combined treatments for cancer therapy is discussed in the light of recent preclinical studies.

Plant phenolics in the prevention and treatment of cancer.

Epidemiological studies indicate that populations consuming high levels of plant derived foods have low incidence rates of various cancers. Recent findings implicate a variety of phytochemicals, including phenolics, in these anticancer properties. Both monophenolic and polyphenolic compounds from a large variety of plant foods, spices and beverages have been shown to inhibit or attenuate the initiation, progression and spread of cancers in cells in vitro and in animals in vivo. The cellular mechanisms that phenolics modulate to elicit these anticancer effects are multi-faceted and include regulation of growth factor-receptor interactions and cell signaling cascades, including kinases and transcription factors, that determine the expression of genes involved in cell cycle arrest, cell survival and apoptosis or programmed cell death. A major focus has been the inhibitory effects of phenolics on the stress-activated NF-KB and AP-1 signal cascades in cancer cells which are regarded as major therapeutic targets. Phenolics can enhance the body's immune system to recognize and destroy cancer cells as well as inhibiting the development of new blood vessels (angiogenesis) that is necessary for tumour growth. They also attenuate adhesiveness and invasiveness of cancer cells thereby reducing their metastatic potential. Augmentation of the efficacy ofstandard chemo- and radiotherapeutic treatment regimes and the prevention of resistance to these agents is another important effect of plant phenolics that warrants further research. Plant phenolics appear to have both preventative and treatment potential in combating cancer and warrant further, in-depth research. It is interesting that these effects of plant phenolics on cancer inhibition resemble effects reported for specific fatty acids (omega-3 PUFA, conjugated linoleic acids). Although phenolic effects in cells in vitro and in animal models are generally positive, observations from the less numerous human interventions are less clear. This is surprising given the positive epidemiological data and may relate to mixed diets and synergistic interactions between compounds or the bioavailability of individual compounds. Much of the work in vitro with phenolic compounds has utilized concentrations higher than the amount that can be obtained from the diet suggesting a role of fortified, functional foods in cancer suppression.

Metabolites are key to understanding health effects of wine polyphenolics.

Phenolic compounds in grapes and wine are grouped within the following major classes: stilbenes, phenolic acids, ellagitannins, flavan-3-ols, anthocyanins, flavonols, and proanthocyanidins. Consumption of foods containing phenolic substances has been linked to beneficial effects toward chronic diseases such as coronary heart disease and colorectal cancer. However, such correlations need to be supported by in vivo testing and bioavailability studies are the first step in establishing cause and effect. Class members from all phenolic groups can be glucuronidated, sulfated, and/or methylated and detected at low concentrations in the bloodstream and in urine. But the majority of phenolic compounds from grapes and wine are metabolized in the gastrointestinal tract, where they are broken down by gut microflora. This typically involves deglycosylation, followed by breakdown of ring structures to produce phenolic acids and aldehydes. These metabolites can be detected in bloodstream, urine, and fecal samples by using sophisticated instrumentation methods for quantitation and identification at low concentrations. The health effects related to grape and wine consumption may well be due to these poorly understood phenolic acid metabolites. This review discusses the known metabolism of each major class of wine and grape phenolics, the means to measure them, and ideas for future investigations.

Genotoxicity studies of a desealant solvent mixture, SR-51.

The Royal Australian Air Force (RAAF) has reported that personnel involved in F-111 fuel tank maintenance were concerned that exposure to a range of chemicals during the period 1977 to mid-1990s was the cause of health problems, including cancer. Particular concern was directed at SR-51, a desealant chemical mixture containing the following four solvents: aromatic 150 solvent (Aro150), dimethylacetamide, thiophenol (TP), and triethylphosphate. The present study examined the mutagenic potential of SR-51 using a range of well-known mutagen and genotoxin assays. The tests used were i) a modified version of the Ames test, ii) the mouse lymphoma assay, iii) the comet assay (a single-cell gel electrophoresis assay), and iv) a mouse micronucleus test. The modified Ames test used mixed bacterial strains in liquid suspension media. The Ames test results showed that SR-51 (tested up to the cytotoxic concentration of 36 microg/ml, 30 min incubation) in the presence and absence of S9 metabolic activation was not mutagenic. The mouse lymphoma assay used cultured mouse lymphoma cells in a microwell suspension method. The mouse lymphoma assay was also negative with SR-51 (tested up to the cytotoxic concentration of 22.5 microg/ml, 3 h incubation) in the presence and absence of S9 metabolic activation. The Comet assay, using cultured mouse lymphoma cells, showed no evidence of DNA damage in cells exposed up to the cytotoxic concentration of SR-51 at 11.25 microg/ml. The in-vivo mouse micronucleus test was undertaken in wild-type C57Bl6J male mice dosed orally with SR-51for 14 days with a single daily dose up to 360 mg/kg/day (the maximum-tolerated dose). No increases were observed in micronuclei (MN) frequency in bone marrow collected (24 h after final dose) from SR-51-treated mice compared to the number of MN observed in bone marrow collected from untreated mice. Tissues collected from treated mice at necropsy demonstrated a significant increase in spleen weights in the high dose mice. Gas chromatography analysis of SR-51 identified more than 40 individual components and an oxidation product, diphenyldisulfide derived from TP under conditions of mild heating. In conclusion, there was no evidence that SR-51 is mutagenic.

Durian (Durio zibethinus Murr.) cultivars as nutritional supplementation to rat's diets.

The properties of Mon Thong, Chani and Kan Yao durian (Durio zibethinus Murr.) cultivars were compared in vitro and in vivo studies in order to find the best one as a supplement to antiatherosclerotic diet. Total polyphenols (361.4+/-35.3 mgGAE/100g FW), flavonoids (93.9+/-8.9 mgCE/100g FW) and total antioxidant capacity determined by DPPH and beta-carotene-linoleic acid assays (261.3+/-25.3 microMTE/100g FW and 77.8+/-7.8% of inhibition) were maximal in Mon Thong in comparison with Chani and Kan Yao and showed a good correlation between these three variables (R(2)=0.9859). Five groups of rats were fed diets supplemented with cholesterol and different durian cultivars. Diets supplemented with Mon Thong and to a lesser degree with Chani and Kan Yao significantly hindered the rise in the plasma lipids (TC - 8.7%, 16.1% and 10.3% and (b) LDL-C - 20.1%, 31.3% and 23.5% for the Chol/Kan Yao, Chol/Mon Thong and Chol/Chani, respectively) and the decrease in plasma antioxidant activity (P<0.05). Nitrogen retention remained significantly higher in Chol/Mon Thong than in other diet groups. Diet supplemented with Mon Thong affected the composition of plasma fibrinogen in rats and showed more intensity in protein bands around 47 kDa. No lesions were found in the examined tissue of heart and brains. Mon Thong cultivar is preferable for the supplementation of the diet as positively influenced the lipid, antioxidant, protein and metabolic status. The durian fruit till now was not investigated extensively, therefore based on the results of this study durian cultivars can be used as a relatively new source of antioxidants.

Evolution and current status of research in phenolic compounds.

Phenolic compounds are ubiquitous in plants which collectively synthesize several thousand different chemical structures characterized by hydroxylated aromatic ring(s). These compounds play several important functions in plants. They represent a striking example of metabolic plasticity enabling plants to adapt to changing biotic and abiotic environments and provide to plant products colour, taste, technological properties and putative health promoting benefits. Phenolic compounds represent the most studied phytochemicals and have been widely exploited as model systems in different areas of plant research. Initial studies in the field concerned the analytical characterization of a wide range of structures and of relevant enzymes with PAL being one of the most studied plant enzymes. This research is still active due to the complexity of the structures and the biosynthetic pathways As an example, the nature and functions of enzymes involved in lignin synthesis have been revisited several times, even in recent years. More recently, molecular biology and genomics have provided additional understanding of the mechanisms underlying the synthesis of these compounds with special emphasis on the regulation of gene expression by environmental factors. The extensive characterization of genes encoding the different enzymatic steps of flavonoid synthesis and cytochrome P450 genes have been among the most recent advances in this area. Metabolic engineering of lignins and flavonoids has been deeply investigated. Significant positive results have been obtained in both areas but the negative European opinion towards genetically modified organisms has considerably hampered potential applications. From a more basic point of view, global approaches (such as transcript and metabolite profiling) have investigated the repercussions of these engineered modulations of specific phenolics synthesis on other branches of plant metabolism. These studies have revealed a substantial and sometimes unexpected network of regulatory interactions. In the present time, the societal demand and an increasing interest for practical applications has stimulated a wide range of biological and epidemiological studies aiming at characterizing the health promoting properties of specific phenolic compounds with antioxidant activities towards cancer, cardiovascular and neurodegenerative diseases or for use in antiaging or cosmetic products. Increased emphasis on sustainable development should stimulate innovative investigations on phenolic synthesis for improving plant biomass and for a better control of plant and animal health.