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Anthocyanidin and flavonol glycosides have been linked to the health-promoting effects associated with apple consumption. However, very few enzymes involved in flavonoid glycosylation have been characterised to date. Here, we present the identification and phylogenetic analysis of 234 putative glycosyltransferases involved in flavonoid biosynthesis, and detail the biochemical and structural characterisation of MdUGT78T2 as a strict galactosyltransferase involved in the formation of quercetin-3-O-galactoside and cyanidin-3-O-galactoside, the major glycoconjugates of flavonoids in apple. The enzyme is also active on other flavonoids but with a lower catalytic efficiency. Our data, complemented with gene expression analysis suggest that MdUGT78T2 synthesises the glycoconjugates at both the early and late stages of fruit development. This newly discovered type of catalytic activity can potentially be exploited for in vitro modification of flavonoids to increase their stability in food products and to modify apple fruits and other commercial crops through breeding approaches to enhance their health benefits., QC 20230630

Inhibition of human topoisomerase I have been shown to reduce excessive transcription of PAMP-induced genes based on prior studies, which offers a solution to offset complications of sepsis such as tissue damage and organ failure. The enzyme resolves the topological constraints on DNA that encodes these genes. The aim of this study is to identify human topoisomerase I (HTop1) inhibitors that can a.) prevent the relaxation of negative supercoiled plasmid DNA by HTop1 and b.) reduce HTop1 binding to DNA and formation of covalent cleavage complex (HTop1cc) utilizing a novel yeast screening system. Top hits from in-silico screening conducted by our collaborator showed moderate to no inhibition. The natural products anthocyanidins, delphinidin, and cyanidin chloride were shown to restore the growth of yeast expressing a lethal HTOP1 mutant by preventing HTop1cc. Myricetin inhibited yeast growth in the presence and absence of HTop1 overexpression, which requires further investigation. This novel yeast screening approach can offer potential insights into the inhibitor’s mechanism of action.

The use of a single family of dietary bioactive compounds has not been sufficient to manage highly regulated mechanisms such as body weight. Therefore, we aimed to evaluate the effect of a multifunctional ingredient (MIX) based on the co-administration of a low dose of conjugated linoleic acid with the protein hydrolysate from chicken feet, Hpp11, and a mixture of grape-seed proanthocyanidins and berry anthocyanins on body weight management in obese rats fed a cafeteria diet. The daily oral administration of the MIX for three weeks significantly reversed obesity and hyperleptinemia and increased energy expenditure and fat oxidation. In addition, animals administered the MIX exhibited greater hypothalamic activation of STAT3 in POMC-expressing neurons than non-supplemented animals. Our results strongly suggest that the co-administration of different bioactive compounds could be a promising strategy to complement the existing therapies against obesity and leptin resistance.

A metabolomics approach based on nuclear magnetic resonance (NMR) spectroscopy, a rapid and simple technique, was used for the assessment of chemical changes of 'Van' sweet cherries during their storage. This approach affords a holistic analysis since NMR spectroscopy allows the simultaneous detection of diverse groups of secondary and primary metabolites, and reflects the real molar levels of the metabolites. Additionally, color parameters L∗, a∗ and b∗, total phenolic content (TPC), total flavonoid content (TFC), anthocyanidins and total antioxidant potential (AOP) were measured. After harvest, cherries were stored at 1°C and sampling was done after 0, 2, 4, 7 and 10 days. Cherry skin was removed, freeze dried and stored at -80°C till analyses. For NMR analyses, freeze dried cherry skins have been extracted with methanol-d4/trifluoroacetic acid-d solvent mixture. For other analyses, samples were extracted in 70% ethanol with 1% of formic acid. The 1D and 2D NMR spectral analysis confirmed that sugars (glucose, fructose, sucrose), organic acids (malic and citric acid), and phenolic compounds (neochlorogenic acid, cyanidin 3-O-rutinoside, and cyanidin 3-O-glucoside) are the main compounds in the cherry skin extracts. The 1H NMR spectral data have been subjected to multivariate analysis. Orthogonal projections to latent structures (OPLS) were applied to correlate the NMR data with the storage time. The changes in chemical composition among the samples with different storage time were clearly visible on the score plot. According to the goodness of fit of the model (R 2 =0.954), and its predictive ability (Q 2 =0.634), cherry skin extracts were well-correlated with the storage time. A positive correlation of the signals corresponding to glucose, neochlorogenic acid, cyanidin 3-O-rutinoside, and cyanidin 3-O-glucoside with the storage time of cherries has been observed on the loading plot. According to the loading plot, the increase in the content of glucose, neochlorog

A metabolomics approach based on nuclear magnetic resonance (NMR) spectroscopy, a rapid and simple technique, was used for the assessment of chemical changes of 'Van' sweet cherries during their storage. This approach affords a holistic analysis since NMR spectroscopy allows the simultaneous detection of diverse groups of secondary and primary metabolites, and reflects the real molar levels of the metabolites. Additionally, color parameters L∗, a∗ and b∗, total phenolic content (TPC), total flavonoid content (TFC), anthocyanidins and total antioxidant potential (AOP) were measured. After harvest, cherries were stored at 1°C and sampling was done after 0, 2, 4, 7 and 10 days. Cherry skin was removed, freeze dried and stored at -80°C till analyses. For NMR analyses, freeze dried cherry skins have been extracted with methanol-d4/trifluoroacetic acid-d solvent mixture. For other analyses, samples were extracted in 70% ethanol with 1% of formic acid. The 1D and 2D NMR spectral analysis confirmed that sugars (glucose, fructose, sucrose), organic acids (malic and citric acid), and phenolic compounds (neochlorogenic acid, cyanidin 3-O-rutinoside, and cyanidin 3-O-glucoside) are the main compounds in the cherry skin extracts. The 1H NMR spectral data have been subjected to multivariate analysis. Orthogonal projections to latent structures (OPLS) were applied to correlate the NMR data with the storage time. The changes in chemical composition among the samples with different storage time were clearly visible on the score plot. According to the goodness of fit of the model (R 2 =0.954), and its predictive ability (Q 2 =0.634), cherry skin extracts were well-correlated with the storage time. A positive correlation of the signals corresponding to glucose, neochlorogenic acid, cyanidin 3-O-rutinoside, and cyanidin 3-O-glucoside with the storage time of cherries has been observed on the loading plot. According to the loading plot, the increase in the content of glucose, neochlorog

[EN] Wine colour is one of the main organoleptic characteristics influencing its quality. It is of special interest in red vinifications due to the economic resources that wineries have to invest for the extraction of the phenolic compounds responsible for wine colour, compounds that are mainly located inside the skin cell vacuoles, where the volatile compounds are also found. The transfer of phenolic compounds from grapes to must during vinification is closely related to the type of grapes and the winemaking technique. During traditional winemaking, grapes are crushed and skin macerated for several days, with pumps overs to facilitate the colour extraction. To increase this extraction, some chemical (maceration enzymes) or physical technologies (thermovinification, cryomaceration, flash-expansion) can be applied. In this work, a new methodology has been tested. This methodology consists in the application of high-power ultrasounds to crushed grapes to increase the extraction of phenolic compounds. Crushed grapes were treated with this non-thermal technology and vinified, with 3, 6 and 8days of skin maceration time, and the results were compared with a control vinification, where crushed grapes were not subjected to any treatment and were skin macerated during 8days. The wine chromatic characteristics (determined spectrophotometrically) and the individual phenolic compounds (anthocyanins and tannins, determined by HPLC) were followed during the maceration period, at the end of alcoholic fermentation and after two months in bottle. Also, the wine volatile compounds were determined by GC-MS. The wines made with ultrasound-treated grapes showed differences with the control wine, especially regarding total phenol content and tannin content. The wines elaborated with sonicated grapes and with only three days of skin maceration time presented similar concentration of anthocyanins and twice the concentration of tannins than control wines elaborated with 8days of skin macer

[EN] Wine colour is one of the main organoleptic characteristics influencing its quality. It is of special interest in red vinifications due to the economic resources that wineries have to invest for the extraction of the phenolic compounds responsible for wine colour, compounds that are mainly located inside the skin cell vacuoles, where the volatile compounds are also found. The transfer of phenolic compounds from grapes to must during vinification is closely related to the type of grapes and the winemaking technique. During traditional winemaking, grapes are crushed and skin macerated for several days, with pumps overs to facilitate the colour extraction. To increase this extraction, some chemical (maceration enzymes) or physical technologies (thermovinification, cryomaceration, flash-expansion) can be applied. In this work, a new methodology has been tested. This methodology consists in the application of high-power ultrasounds to crushed grapes to increase the extraction of phenolic compounds. Crushed grapes were treated with this non-thermal technology and vinified, with 3, 6 and 8days of skin maceration time, and the results were compared with a control vinification, where crushed grapes were not subjected to any treatment and were skin macerated during 8days. The wine chromatic characteristics (determined spectrophotometrically) and the individual phenolic compounds (anthocyanins and tannins, determined by HPLC) were followed during the maceration period, at the end of alcoholic fermentation and after two months in bottle. Also, the wine volatile compounds were determined by GC-MS. The wines made with ultrasound-treated grapes showed differences with the control wine, especially regarding total phenol content and tannin content. The wines elaborated with sonicated grapes and with only three days of skin maceration time presented similar concentration of anthocyanins and twice the concentration of tannins than control wines elaborated with 8days of skin macer

The relationships between structure, spectral characteristics, and colour of the aglycone moiety of cyanidin and its 3-glucosidic substitution in cyanidin 3-O- β-glucopyranoside were studied as a function of pH, using a combination of techniques (UV-Vis spectrophotometry, colorimetry, and HPLC-ESI/MS). The absorption and fluorescence emission spectra of cyanidin and Cy3Glc at pH 5.5 in aqueous solution have been studied. The colour variation, colour intensity and stability at various pH values (2.0, 4.0, 7.0 and 9.0) of cyanidin and Cy3Glc were investigated during a period of 8 hours storage at 25 ± 0.1ºC, as well as, in the aqueous solution at pH 7.0 and under the conditions of the elevated temperature (55.0 ± 0.1ºC) which simulate the rapid food ageing. The interactions of cyanidin and Cy3Glc with model lipid membranes differing in surface charge and phase state were investigated using DSC and fluorescence emission polarization spectrometry.

Cílem diplomové práce byla charakteristika vybraných odrůd tichých vín. V teoretické části se práce zabývá chemickým složením a technologií výroby vína, dále stručným popisem vybraných odrůd tichých vín, vinohradnických oblastí Slovenska a taktéž možnostmi stanovení analytických parametrů vína. K vypracování této práce bylo použito 10 vzorků 9 odrůd vín, pocházejících z Malokarpatské a Jihoslovenské vinohradnické oblasti Slovenska. Analýza vín Dornfelder, Frankovka modrá, Svätovavrinecké, Zweigeltrebe, Müller Thurgau, Veltlínske zelené, Rizling rýnsky, Rizling vlašský a Sauvignon zahrnovala stanovení antokyaninů a polyfenolů spektrofotometricky a pomocí HPLC, stanovení titrovatelných kyselin, hustoty pyknometricky a stanovení trichromatické charakteristiky a barviv v odrůdách červených vín., The aim of this diploma work was focused on characterization of selected varieties of still wines. In the theoretical part, thesis deals with description of the chemical composition and wine production technology. Further, there is discussed a brief description of selected varieties of still wines present in the market, there are defined geographical regions of Slovakia with respect to the wine production, and possibilities of determination of the analytical parameters of wine. For the elaboration of this thesis there was used 10 samples of 9 varieties of wines originating from Malokarpatská "Lesser Carpathian" and Južnoslovenská "Southern Slovak" wine regions of Slovak Republic. Analysis was performed on Dornfelder, Frankovka modrá, Svätovarinecké, Zweigeltrebe, Müller Thurgau, Veltlínské zelené, Rizling rýnsky, Rizling vlašský and Sauvignon wine varieties. It was focused mainly on determination of anthocyanins and polyphenols by means of spectrophotometry and by HPLC techniques, determination of titration acidity, wine density, chromatic characteristics and dyes present in studied red wines., Ústav technologie potravin

Anthocyanidins are bioactive flavonoids with potential health-promoting effects. These may vary among single anthocyanidins considering differences in their bioavailability and some of the mechanisms involved. The aim of the present study was to estimate the dietary intake of anthocyanidins, their food sources and the lifestyle factors (sex, age, BMI, smoking status, educational level and physisical activity) involved among twenty-seven centres in ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthocyanidin intake and their food sources for 36 037 subjects, aged between 35 and 74 years, in twenty-seven redefined centres were obtained using standardised 24 h dietary recall software (EPIC-SOFT). An ad hoc food composition database on anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin) was compiled using data from the US Department of Agriculture and Phenol-Explorer databases and was expanded by adding recipes, estimated values and cooking factors. For men, the total anthocyanidin mean intake ranged from 19.83 (SE 1.53) mg/d (Bilthoven, The Netherlands) to 64.88 (SE 1.86) mg/d (Turin, Italy), whereas for women the range was 18.73 (SE 2.80) mg/d (Granada, Spain) to 44.08 (SE 2.45) mg/d (Turin, Italy). A clear south to north gradient intake was observed. Cyanidins and malvidins were the main anthocynidin contributors depending on the region and sex. Anthocyanidin intake was higher in non-obese older females, non-smokers, and increased with educational level and physical activity. The major food sources were fruits, wine, non-alcoholic beverages and some vegetables. The present study shows differences in both total and individual anthocyanidin intakes and various lifestyle factors throughout Europe, with some geographical variability in their food sources.

Anthocyanidins are bioactive flavonoids with potential health-promoting effects. These may vary among single anthocyanidins considering differences in their bioavailability and some of the mechanisms involved. The aim of the present study was to estimate the dietary intake of anthocyanidins, their food sources and the lifestyle factors (sex, age, BMI, smoking status, educational level and physisical activity) involved among twenty-seven centres in ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthocyanidin intake and their food sources for 36 037 subjects, aged between 35 and 74 years, in twenty-seven redefined centres were obtained using standardised 24 h dietary recall software (EPIC-SOFT). An ad hoc food composition database on anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin) was compiled using data from the US Department of Agriculture and Phenol-Explorer databases and was expanded by adding recipes, estimated values and cooking factors. For men, the total anthocyanidin mean intake ranged from 19.83 (SE 1.53) mg/d (Bilthoven, The Netherlands) to 64.88 (SE 1.86) mg/d (Turin, Italy), whereas for women the range was 18.73 (SE 2.80) mg/d (Granada, Spain) to 44.08 (SE 2.45) mg/d (Turin, Italy). A clear south to north gradient intake was observed. Cyanidins and malvidins were the main anthocynidin contributors depending on the region and sex. Anthocyanidin intake was higher in non-obese older females, non-smokers, and increased with educational level and physical activity. The major food sources were fruits, wine, non-alcoholic beverages and some vegetables. The present study shows differences in both total and individual anthocyanidin intakes and various lifestyle factors throughout Europe, with some geographical variability in their food sources.

In vitro ruminal digestion was conducted on novel "purple-green" alfalfa forage that accumulated anthocyanidin and proanthocyanidins through the expression of a maize bHLH anthocyanidin regulatory gene (Lc). The Lc-transgenic genotypes were compared with parental (non-transformed, NT) alfalfa in their in vitro ruminal fermentation, dry matter (DM) and N disappearances, and DM degradability. The transgenic genotypes expressed the Lc gene at different levels when grown under high light conditions, resulting in anthocyanidin contents as high as 136 mu g g(-1) DM. Lc genotypes had lower true DM disappearance than NT alfalfa at 0, 4 and 12 h of incubation, but not at 24 or 48 h. Compared with NT, Lc-transgenic genotypes had a lower content of rapidly soluble DM, but a similar content and rate of degradation of the slowly degradable DM fraction, and a similar lag time for digestion. True disappearance of N was lower for Lc-transgenic than NT alfalfa at the initiation of the incubation. The solubility of both DM and N were negatively correlated with the concentration of anthocyanidins measured in the forage. The results indicate that Lc-transformation reduced the initial rate, but not the extent of DM and N digestion of alfalfa in the rumen. These properties could improve the utilization of protein and possibly reduce the risk of bloat in ruminants consuming fresh alfalfa. However, further increasing the amount of anthocyanidins (or proanthocyanidins) produced in the forage may be required to make this a viable strategy for improved protein utilization and bloat prevention.

English: The bark of Cassia petersiana afforded the known flavan-f-ols (+)-catechin, (-)- epicatechin, (+)-gallocatechin and epigallocatechin which co-occured with three new procassinidins namely cassiaflavan-( 4ß-8)-gallocatechin, cassiaflavan-( 4a.-8)- epigallocatechin and cassiaflavan-( 4a-8)-epigallocatechin as well as four novel probutinidins namely butiniflavan-( 4a.-8)-epicatechin, butiniflavan-( 4ß~8)- epicatechin, butiniflavan-( 4~8)-epigallocatechin and ent-butiniflavan-( 4J3~8)- epicatechin. A combination of solvent extraction, column (LH20) and thin layer chromatography procedures were used to isolate and purify the compounds mentioned. Structure elucidation was done using high resolution IH NMR spectroscopy which included NOE and COSY experiments in conjunction with FAB-MS. Due to a high degree of rotational isomerism structural assignments of the following compounds cassiaflavan-( 4J3~8)-epigallocatechin, cassiaflavan-( 4a.~8)-epigallocatechin, butiniflavan-( 4a.~8)-epicatechin, butiniflavan-( 4J3~8)-epicatechin, butiniflavan- (4J3~8)-epigallocatechin and ent-butiniflavan-( 4J3~8)-epicatechin were obtained by tedious NMR experiments and CD data hence recourse to synthesis was absolutely essential to confirm the proposed structures beyond any doubt. Biomimetic synthesis of the procassinidin dimers via reduction of the racerrue flavanones, (±)-4',7-di-O-methyIcassinidin to the diastereomeric flavan-e-ols and condensation with 3',4',S',S,7-penta-O-methylepigallocatechin usmg titanium tetrachloride as Lewis acid was used to confirm the structures. A similar biomimetic synthesis of probutinidins via reduction of the racemic flavanones, (±)-3',4',7-tri-O-methylbutin to the diastereomeric flavan-t-ols followed by condensation with 3',4',5,7 -tetra-O-methylepicatechin and 3',4',5',5,7 -penta-Omethylepigallocatechin using titanium tetrachloride as Lewis acid was also employed to confirm the proposed structures. The biornimetic synthesis of probutinidins yielded, Afrikaans: Tydens die huidige studie is die asetoonekstrak van"die bas van Cassia petersiana ondersoek. Die bas van Cassia petersiana het die bekende flavan-f-ole (+)-katesjien, (-)-epi katesjien, (+)-gallokatesjien en epigallokatesjien gelewer wat saam met drie nuwe procassinidiene voorkom, naamlik cassiaflavan-( 4f3~8)-gallokatesj ien, cassiaflavan- (4f3~8)-epigallokatesjien and cassiaflavan-(4a~8)-epigallokatesjien en ook vier on bekende probutinidiene, naamlik butiniflavan-( 4a~8)-epikatesj ien, butiniflavan- (4B~8)-epikatesjien, butiniflavan-( 4B~8)-epigallokatesj ien en ent-butiniflavan- (4B~8)-epikatesj ien. 'n Kombinasie van oplosrniddelekstrahering, kolom (LH20) en dun laag chromatografie metodes is gebruik om die gemelde verbindings te isoleer en te suiwer. Struktuuropklarings is gedoen met hoë resolusie IH KMR spektroskopie wat NOE en COSYeksperimente ingesluit het te same met FAB-MS. Te wyte aan die hoë mate van rotasieisomerie is die struktuuropklaring van die volgende verbindings, nl.cassiaflavan- (4f3~8)-epigallokatesjien, cassiaflavan-( 4a~8)-epigallokatesjien, butiniflavan- (4a~8)-epikatesjien, butiniflavan-( 4f3~~)-epikatesjien, butiniflavan-( 4f3~8)- epigallokatesjien en ent-butiniflavan-(4f3~8)-epikatesjien baie bemoeilik en nieteenstaande uitgebreide KMR eksperimente en SD data moes toevlug geneem word tot sintese om die voorgestelde strukture sonder enige twyfel te bevestig. Biornimetiese sintese van die procassinidien dimere via reduksie van die raserruese flavanoon, (±)-{ 7-di-O-metielcassinidien na die diastereomeriese flavan-ë-ole en kondensasie met 3',{5',5,7-penta-O-metielepigallokatesjien is met titaniumtetrachloried as Lewis suur gedoen om die strukture te bevestig. Soortgelyke biomimetiese sintese van probutinidiene via reduksie van die rasemiese flavanoon, (±)-3',{ 7-tri-O-metielbutin na die diastereomeriese flavan-d-ole en kondensasie met 3',{5,7-tetra-O-metielepikatesjien en 3',{5',5,7-penta-Ometielepigallokatesjien is ook met titan

Anthocyane, eine Untergruppe der Flavonoide, sind als natürliche Farbpigmente weit verbreitet in Lebensmitteln pflanzlicher Herkunft. Ihnen werden eine Reihe von gesundheitlich positiven Wirkungen zugeschrieben, was dazu geführt hat, dass auf dem Markt für Nahrungsergänzungsmittel immer mehr Produkte auf Anthocyanbasis auftauchen. Als ein möglicher nachteiliger Faktor für eine potentielle genotoxische Wirkung von Flavonoiden wird die Interaktion mit humanen Topoisomerasen diskutiert. Bezüglich einer möglichen Risiko/Nutzen-Evaluierung ist es nicht nur von Bedeutung, ob Flavonoide/Anthocyane mit diesen Enzymen interagieren, sondern auch die Art dieser Interaktion und sich möglicherweise daraus ergebende Konsequenzen, besonders im Hinblick auf die Integrität der DNA. Ziel der vorliegenden Arbeit war es, die Anthocyanidine Delphinidin (Del), Cyanidin (Cy), Pelargonidin (Pg), Paeonidin (Pn) und Malvidin (Mv) hinsichtlich ihrer Beeinflussung humaner Topoisomerase I und II zu untersuchen. Ein Schwerpunkt lag bei der Aufklärung des Wirkmechanismus dieser Verbindungen bezüglich einer Stabilisierung des Cleavable Complex, möglichen Interaktionen mit der DNA und die Relevanz dieser Effekte für die Integrität zellulärer DNA. Es konnte gezeigt werden, dass nur die Verbindungen mit vicinalen Hydroxygruppen im B-Ring des Anthocyangrundgerüstes, Del und Cy, effektiv die katalytische Aktivität isolierter humaner Topoisomerase I und Topoisomerase IIalpha + IIbeta hemmen. Sie wirken jedoch nicht wie die klassischen Topoisomerasegifte Camptothecin oder Etoposid über die Stabilisierung des kovalenten Topoisomerase-DNA-Komplexes, sondern stellen rein katalytische Inhibitoren dar. Del und Cy könnten sogar die DNA vor Topoisomerase I-Giften schützen, da sie zumindest am isolierten Enzym die Stabilisierung des Cleavable Complex der Topoisomerase I durch Camptothecin effektiv verhindern. Für alle getesteten Anthocyanidine konnte gezeigt werden, dass sie im niedrigen mikromolaren Bereich, zw, In the present study we investigated the effect of the anthocyanidins delphinidin (DEL), cyanidin (CY), pelargonidin (PG), paeonidin (PN) and malvidin (MV) on human topoisomerases I and II and its relevance for DNA integrity within human cells. We especially focused on the mechanism of interaction with the target enzyme, particularly the stabilization of the covalent DNA-topoisomerase-intermediate (cleavable complex), possible interactions with DNA and the potential relevance for DNA integrity within human cells. Anthocyanidins bearing vicinal hydroxyl groups at the B-ring, DEL and CY, were found to potently inhibit the catalytic activity of human topoisomerases I and II, without discriminating between the IIalpha and IIbeta isoforms. However, in contrast to topoisomerase poisons, DEL and CY did not stabilize the cleavable complex. Using recombinant topoisomerase I, the presence of CY or DEL (> 1 µM) effectively prohibited the stabilization of the cleavable complex by the topoisomerase I poison camptothecin. In contrast, the stabilization of the topoisomerase II cleavable complex by etoposide remained unaffected. Using a fluorescence competition assay with ethidiumbromide or Hoechst 33258, it could be shown that at all analogues were able to compete with ethidium bromide for the intercalation into calf thymus DNA or to replace the minor groove binder Hoechst 33258. Furthermore it could be shown that at concentrations > 50 µM all anthocyanidins tested (delphinidin, cyanidin, malvidin, pelargonidin, paeonidin), including those not interfering with topoisomerases, were found to induce DNA strand breaks in the comet assay. These data indicate substantial affinity to double stranded DNA, which might contribute at least to the DNA strand breaking effect of anthocyanidins. The effect of anthocyanidins on DNA integrity appears to depend on the concentration range. A second focus of the present study was the influence of an overexpression of the tyrosyl-DNA-phosphodiesterase