A novel biflavonoid from roots of Glycyrrhiza uralensis cultivated in China.
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A novel biflavonoid named licobichalcone was isolated from the roots of Glycyrrhiza uralensis cultivated in China, along with twelve known compounds, including five chalcones, two isoflavones, two flavanones, two flavones and one pterocarpan. Their structures were respectively elucidated on the basis of chemical and spectroscopic evidence. (+info)
Mechanism of action of the antiherpesvirus biflavone ginkgetin.
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Screening of plant extracts found that a biflavone from Cephalotaxus drupacea, which was found to be ginkgetin, is active against herpes simplex virus type 1 (HSV-1). This compound caused dose-dependent inhibition of virus replication with a 50% cytotoxic activity at 12.8 micrograms/ml and 50% anti-HSV-1 activity at 0.91 micrograms/ml, the therapeutic index being 14.1. Ginkgetin also showed inhibitory effects against HSV type 2 and human cytomegalovirus with therapeutic indices of 13.8 and 11.6, respectively. Ginkgetin had a weak virucidal activity against HSV-1 at more than 5 micrograms/ml. Both adsorption of HSV-1 to host cells and virus penetration into cells were unaffected by this agent. Ginkgetin suppressed viral protein synthesis when added at various steps of HSV-1 replication and exerted strong inhibition of transcription of the immediate-early genes. (+info)
Epicatechin, catechin, and dimeric procyanidins inhibit PMA-induced NF-kappaB activation at multiple steps in Jurkat T cells.
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The capacity of the flavan-3-ols [(-)-epicatechin (EC) and (+)-catechin (CT)] and a B dimeric procyanidin (DP-B) to modulate phorbol 12-myristate 13-acetate (PMA)-induced NF-kappaB activation in Jurkat T cells was investigated. The classic PMA-triggered increase in cell oxidants was prevented when cells were preincubated for 24 h with EC, CT, or DP-B (1.7-17.2 microM). PMA induced the phosphorylation of IKKbeta and the subsequent degradation of IkappaBalpha. These events were inhibited in cells pretreated with the flavonoids. PMA induced a 4.6-fold increase in NF-kappaB nuclear binding activity in control cells. Pretreatment with EC, CT, or DP-B decreased PMA-induced NF-kappaB binding activity and the transactivation of the NF-kappaB-driven gene IL-2. EC, CT, and DP-B inhibited, in vitro, NF-kappaB binding to its DNA consensus sequence, but they had no effect on the binding activity of CREB or OCT-1. Thus, EC, CT, or DP-B can influence the immune response by modulating NF-kappaB activation. This modulation can occur at early (regulation of oxidant levels, IKK activation) as well as late (binding of NF-kappaB to DNA) stages of the NF-kappaB activation cascade. A model is presented for possible interactions between DP-B and NF-kappaB proteins, which could lead to the inhibition of NF-kappaB binding to kappaB sites. (+info)
Inhibition of angiotensin converting enzyme (ACE) activity by flavan-3-ols and procyanidins.
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It was determined that flavan-3-ols and procyanidins have an inhibitory effect on angiotensin I converting enzyme (ACE) activity, and the effect was dependent on the number of epicatechin units forming the procyanidin. The inhibition by flavan-3-ols and procyanidins was competitive with the two substrates assayed: N-hippuryl-L-histidyl-L-leucine (HHL) and N-[3-(2-furyl)acryloyl]-L-phenylalanylglycylglycine (FAPGG). Tetramer and hexamer fractions were the more potent inhibitors, showing Ki of 5.6 and 4.7 microM, respectively. As ACE is a membrane protein, the interaction of flavanols and procyanidins with the enzyme could be related to the number of hydroxyl groups on the procyanidins, which determine their capacity to be adsorbed on the membrane surface. (+info)
Cancer prevention by tea polyphenols is linked to their direct inhibition of antiapoptotic Bcl-2-family proteins.
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Epidemiological data and in vitro studies on cancer chemoprevention by tea polyphenols have gained attention recently from the scientific community, nutritionists, the pharmaceutical industry, and the public. Despite the several efforts made recently to elucidate the molecular basis for the anticancer activity of these natural products, little correlation has been found thus far between the putative protein targets of compounds found in tea extracts and levels found in plasma after tea consumption. Here, by using a combination of nuclear magnetic resonance binding assays, fluorescence polarization assay, and computational docking studies, we found that certain green tea catechins and black tea theaflavins are very potent inhibitors (K(i) in the nanomolar range) of the antiapoptotic Bcl-2-family proteins, Bcl-x(L) and Bcl-2. These data suggest a strong link between the anticancer activities of these tea polyphenols and their inhibition of a crucial antiapoptotic pathway, which is implicated in the development of many human malignancies. (+info)
Suppression of estrogen biosynthesis by procyanidin dimers in red wine and grape seeds.
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In breast cancer, in situ estrogen production has been demonstrated to play a major role in promoting tumor growth. Aromatase is the enzyme responsible for the conversion of androgen substrates into estrogens. This enzyme is highly expressed in breast cancer tissue compared with normal breast tissue. A wine extract fraction was recently isolated from red wine that exhibited a potent inhibitory action on aromatase activity. Using UV absorbance analysis, high-performance liquid chromatography profiling, accurate mass-mass spectrometry, and nanospray tandem mass spectrometry, most of the compounds in our red wine fraction were identified as procyanidin B dimers that were shown to be aromatase inhibitors. These chemicals have been found in high levels in grape seeds. Inhibition kinetic analysis on the most potent procyanidin B dimer has revealed that it competes with the binding of the androgen substrate with a K(i) value of 6 micro M. Because mutations at Asp-309, Ser-378, and His-480 of aromatase significantly affected the binding of the procyanidin B dimer, these active site residues are thought to be important residues that interact with this phytochemical. The in vivo efficacy of procyanidin B dimers was evaluated in an aromatase-transfected MCF-7 breast cancer xenograft model. The procyanidin B dimers were able to reduce androgen-dependent tumor growth, indicating that these chemicals suppress in situ estrogen formation. These in vitro and in vivo studies demonstrated that procyanidin B dimers in red wine and grape seeds could be used as chemopreventive agents against breast cancer by suppressing in situ estrogen biosynthesis. (+info)
Delivery of tea polyphenols to the oral cavity by green tea leaves and black tea extract.
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Catechins and theaflavins, polyphenolic compounds derived from tea (Camellia sinensis, fam. Theaceae), have been reported to have a wide range of biological activities including prevention of tooth decay and oral cancer. The present study was undertaken to determine the usefulness of green tea leaves and black tea extract for the delivery of catechins and theaflavins to the oral cavity. After holding either green tea leaves (2 g) or brewed black tea (2 g of black tea leaves in 100 ml) in the mouth for 2-5 min and thoroughly rinsing the mouth, high concentrations of catechins (C(max) = 131.0-2.2 micro M) and theaflavins (C(max) = 1.8-0.6 micro M) were observed in saliva in the 1st hour. Whereas there was significant interindividual variation in the peak levels of catechins and theaflavins, the overall kinetic profile was similar, with t(1/2) = 25-44 min and 49-76 min for catechins and theaflavins, respectively (average coefficient of variation in t(1/2) was 23.4%). In addition to the parent catechin and theaflavin peaks, five unidentified peaks were also observed in saliva after black tea treatment. Hydrolysis of theaflavin gallates, apparently by salivary esterases, was observed in vitro and in vivo. These results indicate that tea leaves can be used as a convenient, slow-release source of catechins and theaflavins and provide information for the possible use of tea in the prevention of oral cancer and dental caries. (+info)
Theaflavin-3,3'-digallate and penta-O-galloyl-beta-D-glucose inhibit rat liver microsomal 5alpha-reductase activity and the expression of androgen receptor in LNCaP prostate cancer cells.
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Androgens play a critical role in regulating the growth, differentiation and survival of epithelial cells in many androgen-responsive organs, such as prostate and skin. The enzyme steroid 5alpha-reductase (EC 1.3.99.5) catalyzes the conversion of testosterone (T) to a more active androgen, dihydrotestosterone (DHT). DHT then binds to androgen receptors (AR) and functions in the nucleus to regulate specific gene expression. Androgens via their cognate receptor may be involved in the development and progression of benign prostate hyperplasia, prostate cancer, hirsutism, male pattern alopecia and acne. The aim of this study was to determine whether theaflavin-3,3'-digallate (TF3) and penta-O-galloyl-beta-D-glucose (5GG) have inhibitory effects on androgen production and action. We found that TF3 and 5GG inhibit rat liver microsomal 5alpha-reductase activity. Furthermore, TF3 and 5GG significantly reduced androgen-responsive LNCaP prostate cancer cell growth, suppressed expression of the AR and lowered androgen-induced prostate-specific antigen secretion and fatty acid synthase protein level. In conclusion, our result suggests that TF3 and 5GG might be useful chemoprevention agents for prostate cancer through suppressing the function of androgen and its receptor. (+info)