Yu Wang

Polyphenolic chemistry of tea and coffee: a century of progress.

Tea and coffee, the most popular beverages in the world, have been consumed for thousands of years for their alluring flavors and health benefits. Polyphenols, particularly flavonoids and phenolic acids, are of great abundance in tea and coffee and contribute a lot to their flavor and health properties. This paper reviews the polyphenol chemistry of tea and coffee, specifically their stability, and scavenging ability of reactive oxygen species (ROS) and reactive carbonyl species (RCS). During the manufacturing and brewing process, green tea and black tea polyphenols undergo epimerization and oxidation, respectively. Meanwhile, the lactonization and the polymerization of chlorogenic acid are the major causes for the degradation of polyphenols in coffee. Tea catechins, besides having antioxidant properties, have the novel characteristic of trapping reactive carbonyl species. The A ring of the catechins is the binding site for RCS trapping, whereas the B ring is the preferred site for antioxidation.

Chemoprevention of colonic tumorigenesis by dietary hydroxylated polymethoxyflavones in azoxymethane-treated mice

SCOPE Hydroxylated polymethoxyflavones (PMFs), existing exclusively in citrus genus, have been reported to exhibit a broad spectrum of biological activity. Here we investigated the chemopreventive effects and underlying molecular mechanisms of dietary administration of hydroxylated PMFs in an azoxymethane (AOM)-induced colonic tumorigenesis model. METHODS AND RESULTS Male, Institute of Cancer Research (ICR), mice at age of 6 wk were injected with AOM twice weekly at a dose of 5 mg/kg for 2 wk and continuously fed control diet or diets containing 0.01 and 0.05% hydroxylated PMFs, respectively. Mice were then sacrificed at 6 and 20 wk, and colonic tissues were collected and examined. Hydroxylated PMFs feeding dose-dependently decreased the number of aberrant crypt foci in colonic tissues of mice. More importantly, we found that hydroxylated PMFs caused a strong reduction in numbers of large aberrant crypt foci and tumors in colonic tissue. Molecular analysis exhibited the anti-proliferative, anti-inflammatory, anti-angiogenic and pro-apoptotic activities of hydroxylated PMFs by significantly decreasing the levels of inducible nitric oxide synthase, cyclooxygenase, cyclin D1 and vascular endothelial growth factor through interfering with Wnt/β-catenin and epidermal growth factor receptor/Ras/mitogen-activated protein kinase signaling pathways as well as the activation of transcription factors NF-κB and STAT3 in colonic tissue, thus resulting in suppression of colonic tumorigenesis. CONCLUSION Taken together, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary hydroxylated PMFs against AOM-induced colonic tumorigenesis.

Formation of 2,5-Dimethyl-4-hydroxy-3(2H)-furanone through Methylglyoxal: A Maillard Reaction Intermediate

The caramel-like aroma compound, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) was quantified and verified by HPLC and GC-MS in the Maillard reaction based on methylglyoxal (MG). The reaction was performed in the 0.5 M phosphate buffer by heating MG with or without either glycine or cysteine at 120 degrees C for 1 h. MG alone or MG with cysteine could produce increased level of DMHF with pH increased, whereas MG with glycine had contrary trend. Experiments using a 1:1 mixture of [(13)C6]glucose and [(12)C6]glucose indicate that in the presence of glycine or cysteine, glucose skeleton kept intact during DMHF formation since a 1:1 mixture of [(13)C6]DMHF and [(12)C6]DMHF was formed. Acetylformoin was detected in the glucose with amino acid reaction system as a precursor of DMHF, while in the MG reaction systems, acetylformoin could not be identified. It is suggested different pathways of DMHF formation via MG and glucose.

Potential of Natural Products in the Inhibition of Adipogenesis through Regulation of PPARγ Expression and/or Its Transcriptional Activity

Obesity is a global health problem characterized as an increase in the mass of adipose tissue. Adipogenesis is one of the key pathways that increases the mass of adipose tissue, by which preadipocytes mature into adipocytes through cell differentiation. Peroxisome proliferator-activated receptor γ (PPARγ), the chief regulator of adipogenesis, has been acutely investigated as a molecular target for natural products in the development of anti-obesity treatments. In this review, the regulation of PPARγ expression by natural products through inhibition of CCAAT/enhancer-binding protein β (C/EBPβ) and the farnesoid X receptor (FXR), increased expression of GATA-2 and GATA-3 and activation of the Wnt/β-catenin pathway were analyzed. Furthermore, the regulation of PPARγ transcriptional activity associated with natural products through the antagonism of PPARγ and activation of Sirtuin 1 (Sirt1) and AMP-activated protein kinase (AMPK) were discussed. Lastly, regulation of mitogen-activated protein kinase (MAPK) by natural products, which might regulate both PPARγ expression and PPARγ transcriptional activity, was summarized. Understanding the role natural products play, as well as the mechanisms behind their regulation of PPARγ activity is critical for future research into their therapeutic potential for fighting obesity.

Metabolism of flavonoids.

Flavonoids, the most abundant polyphenolic compounds in foods, can be classified into flavanols, flavones, flavonols, flavanones, isoflavones and anthocyanidins. They have been demonstrated to possess strong antioxidant and disease-preventing properties especially for various degenerative diseases such as cancers and cardiovascular diseases in in vitro and in vivo models. However, flavonoids undergo metabolic transformation such as methylation, sulfation and glucuronidation, and consequently changes of their structures and biological activities. In order to reveal a relationship between parent compounds and their metabolites, the changes of structure and bioactivity of various flavonoids are reviewed in the vitro and vivo models.

Lutein from ozone-treated corn retains antimutagenic properties.

The present study was conducted to determine the influence of an ozonation process on lutein and protein in clean and contaminated corns. This study aimed to determine the levels of lutein and protein in corn before and after ozonation and to verify the antimutagenic potential of the extracted lutein against aflatoxin using the Ames test. The lutein content was analyzed by high-performance liquid chromatography. Nitrogen analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis were used to analyze protein. Clean ozone-treated corn had a total lutein content of 28.36 microg/g, which was higher than that of 22.75 microg/g in the untreated clean corn. However, the lutein content was 11.69 microg/g in the ozone-treated contaminated corn, which was lower than that of 16.42 microg/g in the untreated contaminated corn. In both corn samples, the protein content of ozone-treated corn was lower than that of untreated corn, indicating that protein could be destroyed by the ozonation process, which may influence the nutritious value of the corn. Lutein extracts alone showed no mutagenic potential against Salmonella typhimurium tester strains TA100. Lutein extracts from corn inhibited the mutagenicity of AFB1 in a dose-response manner more efficiently than lutein standard. Lutein extracts from different corn samples had similar antimutagenic potentials against AFB1, so the ozone treatment did not affect the antimutagenic potentials of lutein extracts.

Antitumor Activity of Garcinol in Human Prostate Cancer Cells and Xenograft Mice

Garcinol, which is isolated from fruit rinds of Garcinia indica, is a polyisoprenylated benzophenone. It has been studied for its antitumor activity by inducing apoptosis and inhibiting autophagy in human prostate cancer cells. The Bax/Bcl-2 ratio increased when garcinol was applied to PC-3 cells indicating a presence of apoptosis. Meanwhile, procaspases-9 and -3 were suppressed with attenuating PARP and DFF-45. Autophagy was inhibited through activating p-mTOR and p-PI3 Kinase/AKT by garcinol, which as a result induced the cells to apoptosis directly. In addition, the apoptosis effect of garcinol in a xenograft mouse model was also tested, suggesting a consistent result with PC-3 cell model. The tumor size was reduced more than 80 percent after the mouse accepted the garcinol treatment. Garcinol was demonstrated to have a strong antitumor activity through inhibiting autophagy and inducing apoptosis, which was discovered for the first time. Based on these findings, our data suggests that garcinol deserves further investigation as a potent chemopreventive agent.

Reactive Carbonyl Species Derived from Omega-3 and Omega-6 Fatty Acids.

Inflammation-related reactive oxygen species (ROS) and reactive nitrogen species (RNS) are associated with the development of cancer. ROS and RNS can directly damage biomacromolecules such as proteins, DNA, and lipids. Lipid peroxidation, however, can result in reactive carbonyl species (RCS) that can also modify proteins and DNA. In contrast to an extensive literature on the modification of proteins and DNA from omega-6 fatty acids, there are few studies on RCS generation from other fatty acids, particularly omega-3 fatty acids, which are frequently consumed from the diet and diet supplements. Therefore, a comparison between omega-3 and omega-6 fatty acids has been conducted. LC-MS/MS analysis of carbonyl-dinitrophenylhydrazine (DNPH) standards yielded characteristic fragment ions. Autoxidation products of α-linolenic acid and linoleic acid were then derivatized with DNPH and analyzed by LC-MS/MS. The results showed that α-linolenic acid, an omega-3 fatty acid, generated more acrolein and crotonaldehyde than did linoleic acid, an omega-6 fatty acid. Omega-3 fatty acids might be easily degraded to smaller monoaldehydes or dicarbonyls. Omega-3 fatty acids have been considered as health improvement components for a long time. However, on the basis of the results presented here, use of omega-3 fatty acids should be re-evaluated in vivo for safety purposes.

Identification and Quantification of Potential Anti-inflammatory Hydroxycinnamic Acid Amides from Wolfberry

Wolfberry or Goji berry, the fruit of Lycium barbarum, exhibits health-promoting properties that leads to an extensive study of their active components. We synthesized a set of hydroxycinnamic acid amide (HCCA) compounds, including trans-caffeic acid, trans-ferulic acid, and 3,4-dihydroxyhydrocinnamic acid, with extended phenolic amine components as standards to identify and quantify the corresponding compounds from wolfberry and to investigate anti-inflammatory properties of these compounds using in vitro model. With optimized LC-MS/MS and NMR analysis, nine amide compounds were identified from the fruits. Seven of these compounds were identified in this plant for the first time. The amide compounds with a tyramine moiety were the most abundant. In vitro studies indicated that five HCCA compounds showed inhibitory effect on NO production inuded by lipopolysaccharides with IC50 less than 15.08 μM (trans-N-feruloyl dopamine). These findings suggested that wolfberries demonstrated anti-inflammatory properties.

Gymnemic Acids Inhibit Sodium-Dependent Glucose Transporter 1

To evaluate the activity of botanicals used in Chinese Traditional Medicine as hypoglycemic agents for diabetes type II prevention and/or treatment, extracts prepared from 26 medicinal herbs were screened for their inhibitory activity on sodium-dependent glucose transporter 1 (SGLT1) by using two-electrode voltage-clamp recording of glucose uptake in Xenopus laevis oocytes microinjected with cRNA for SGLT1. Showing by far the strongest SGLT1 inhibitory effect, the phytochemicals extracted from Gymnema sylvestre (Retz.) Schult were located by means of activity-guided fractionation and identified as 3-O-β-D-glucuronopyranosyl-21-O-2-tigloyl-22-O-2-tigloyl gymnemagenin (1) and 3-O-β-D-glucuronopyranosyl-21-O-2-methylbutyryl-22-O-2-tigloyl gymnemagenin (2) by means of LC-MS/MS, UPLC-TOF/MS, and 1D/2D-NMR experiments. Both saponins exhibited low IC50 values of 5.97 (1) and 0.17 μM (2), the latter of which was in the same range as found for the high-affinity inhibitor phlorizin (0.21 μM). As SGLT1 is found in high levels in brush-border membranes of intestinal epithelial cells, these findings demonstrate for the first time the potential of these saponins for inhibiting electrogenic glucose uptake in the gastrointestinal tract.