Cytoprotective effects of creosote bush (Larrea tridentata) and Southern live oak (Quercus virginiana) extracts against toxicity induced by venom of the black-tailed rattlesnake (Crotalus ornatus).

The venom of Crotalus ornatus (vCo) poses a threat to human health, as it contains a mixture of toxins that can cause cytotoxic, necrotic, and hemolytic effects. The present study assessed methanolic and acetone extracts from leaves and flowers of Larrea tridentata, as well as the bark of Quercus virginiana as potential suppressors of the toxic effects of vCo in vitro. The content of total phenols, flavonoids, and tannins of the plant extracts were quantified for the suppression of vCo cytotoxicity in two cell culture models, human lymphocytes and porcine aortic endothelial (PAE) cells. Extracts from Q. virginiana displayed a greater concentration of total phenols, flavonoids, and tannins. Co-incubation of lymphocytes and PAE cells with fixed concentrations of vCo and plant extracts resulted in decreased vCo-induced cytotoxicity. A 24-hour co-incubation of lymphocytes with vCo (2.36 ± 0.17 µg/mL) and 0.5 µg/mL of methanolic leaf extract from L. tridentata (LLM) significantly suppressed the venom-induced cytotoxicity by 37.33 ± 8.33%. Similarly, the LLM extract (4 µg/mL) caused a significant decrease in vCo cytotoxicity after 24 hours in PAE cells. In contrast, while the acetone extract of Q. virginiana bark (QA) suppressed cytotoxicity by 29.20 ± 3.51% (p < 0.001) in lymphocytes, it failed to protect PAE cells against vCo after 24 hours. In PAE cells, a shorter 4-hour co-incubation showed significant suppression of cytotoxicity with both extracts. Our results collectively suggest that LLM and QA possess cytoprotective properties against the in vitro toxic effects of vCo, and thus establish extracts from these plants as potential therapeutic interventions against Crotalus envenomation.

Synergistic Interactions between Tocol and Phenolic Extracts from Different Tree Nut Species against Human Cancer Cell Lines.

Tree nuts are rich in polar (phenolic compounds) and non-polar (tocols) antioxidants, with recognized effects in the prevention of diseases such as cancer. These biomolecules possess antiproliferative activity on cancer cells; however, the combined effect of both types of compounds has been scarcely studied, and this approach could give valuable information on the real anticancer potential of tree nuts. In the present study, the antiproliferative activity of pure tocols and phenolic compounds, tocol- and phenolic-rich extracts (TRE and PRE, respectively) from tree nuts and the extracts combinations, was evaluated in four cancer (HeLa, MCF7, PC3, A549) and one control (ARPE) cell lines. The most sensible cell lines were HeLa and MCF7. TRE and PRE from nuts were chemically characterized; γ and δ tocopherols, total tocols, total tocopherols and total phenolic compounds were negatively correlated with cell viability in MCF7 cells. In HeLa cells, only δ and total tocopherols were negatively correlated with cell viability. TRE and PRE had a low effect in reducing cell viability of the cancer cell lines, the most effective extracts were those of emory oak acorn (EOA), pecan nut (PEC) and walnut (WAL), and these were further studied for their pharmacological interactions, using the combination index and the isobologram methods. Combinations of both extracts showed a synergistic and strongly synergistic behavior in the three nuts (EOA, PEC and WAL), with combination indexes between 0.12 and 0.55. These results highlight the need to understand the interactions among components found in complex natural extracts or food products in order to fully understand their bioactivities.

Dehiscence and prolonged storage of 'Kerman' Pistachios: Effects on morphometry and nutraceutical value.

'Kerman' pistachios (KP; Pistacia vera L.) are an important crop for several countries but their commercial value is diminished by their shell dehiscence status and prolonged storage in popular marketplaces. The aim was to evaluate the independent/synergistic effect of prolonged storage (1-4 year) and dehiscence status (split/unsplit) on KP's morphometry and chemical composition. Whole nut's and kernel's length, width, thickness, surface area, and volume were more affected by dehiscence (split > unsplit; p ≤ 0.01) than storage time; Kernel's mass, macronutrient composition and tocopherols (T)/tocotrienols (T3) were not much affected by dehiscence but time-trend correlations were observed with macronutrient composition (split/unsplit; ρ = - 0.57-0.42) and T + T3 (unsplit; ρ = 0.81). Specific/total fatty acids were affected by a complex dehiscence × storage time interaction, and they linearly correlated with certain morphometric characteristics (r ≥ 0.6). Shell dehiscence status more than prolonged storage substantially modifies KP's quality.

Stability and anti-topoisomerase activity of phenolic compounds of Capsicum annuum "Serrano" after gastrointestinal digestion and in vitro colonic fermentation.

"Serrano" pepper is extensively used in Mexican cuisine. The aim of this study was to identify the bioaccessible phenolic compounds (PC) of "Serrano" pepper as well as short-chain fatty acids (SCFA) produced and PC bioconverted using an in vitro step-wise gastromimetic model of the intestinal digestion and anaerobic fermentation of the isolated indigestible fraction (IF). The anti-topoisomerase activity of the fermented samples was also evaluated. PC bioaccessibility was about 45% in the small intestine. Chlorogenic acid and capsaicin were identified during the intestinal digestion, while quercetin was identified as available to the gut microbiota. After 48-h fermentation, SCFA molar ratio was 77:11:12 for acetic, propionic and butyric acid. The PC identified in IF and after 12 h of fermentation showed anti-topoisomerase activity. A synergistic effect among the PC and gut metabolites mixture was observed, which indicates a possible antiproliferative mechanism that should be tested in further studies.

Is Chickpea a Potential Substitute for Soybean? Phenolic Bioactives and Potential Health Benefits.

Legume seeds are rich sources of protein, fiber, and minerals. In addition, their phenolic compounds as secondary metabolites render health benefits beyond basic nutrition. Lowering apolipoprotein B secretion from HepG2 cells and decreasing the level of low-density lipoprotein (LDL)-cholesterol oxidation are mechanisms related to the prevention of cardiovascular diseases (CVD). Likewise, low-level chronic inflammation and related disorders of the immune system are clinical predictors of cardiovascular pathology. Furthermore, DNA-damage signaling and repair are crucial pathways to the etiology of human cancers. Along CVD and cancer, the prevalence of obesity and diabetes is constantly increasing. Screening the ability of polyphenols in inactivating digestive enzymes is a good option in pre-clinical studies. In addition, in vivo studies support the role of polyphenols in the prevention and/or management of diabetes and obesity. Soybean, a well-recognized source of phenolic isoflavones, exerts health benefits by decreasing oxidative stress and inflammation related to the above-mentioned chronic ailments. Similar to soybeans, chickpeas are good sources of nutrients and phenolic compounds, especially isoflavones. This review summarizes the potential of chickpea as a substitute for soybean in terms of health beneficial outcomes. Therefore, this contribution may guide the industry in manufacturing functional foods and/or ingredients by using an undervalued feedstock.

Mango phenolics increase the serum apolipoprotein A1/B ratio in rats fed high cholesterol and sodium cholate diets.

BACKGROUND: Serum lipoproteins are in dynamic equilibrium, partially controlled by the apolipoprotein A1 to apolipoprotein B ratio (APOA1/APOB). Freeze-dried mango pulp (FDM) is a rich source of phenolic compounds (MP) and dietary fiber (MF), although their effects on lipoprotein metabolism have not yet been studied. RESULTS: Thirty male Wistar rats were fed with four different isocaloric diets (3.4 kcal g-1 ) for 12 weeks: control diet, high cholesterol (8 g kg-1 ) + sodium cholate (2 g kg-1 ) diet either alone or supplemented with MF (60 g kg-1 ), MP (1 g kg-1 ) or FDM (50 g kg-1 ). MP and FDM reduced food intake, whereas MF and MP tended to increase serum APOA1/APOB ratio, independently of their hepatic gene expression. This suggests that lipoprotein metabolism was favorably altered by mango bioactives, MP also mitigated the non-alcoholic steatohepatitis that resulted from the intake of this diet. CONCLUSION: We propose that phenolics are the most bioactive components of mango pulp, acting as anti-atherogenic and hepatoprotective agents, with a mechanism of action tentatively based on changes to the main protein components of lipoproteins. © 2018 Society of Chemical Industry.

In vitro Inhibition of Pancreatic Lipase by Polyphenols:A Kinetic, Fluorescence Spectroscopy and Molecular Docking Study.

The inhibitory activity and binding characteristics of caffeic acid, p-coumaric acid, quercetin and capsaicin, four phenolic compounds found in hot pepper, against porcine pancreatic lipase activity were studied and compared to hot pepper extract. Quercetin was the strongest inhibitor (IC50=(6.1±2.4) µM), followed by p-coumaric acid ((170.2±20.6) µM) and caffeic acid ((401.5±32.1) µM), while capsaicin and a hot pepper extract had very low inhibitory activity. All polyphenolic compounds showed a mixed-type inhibition. Fluorescence spectroscopy studies showed that polyphenolic compounds had the ability to quench the intrinsic fluorescence of pancreatic lipase by a static mechanism. The sequence of Stern-Volmer constant was quercetin, followed by caffeic and p-coumaric acids. Molecular docking studies showed that caffeic acid, quercetin and p-coumaric acid bound near the active site, while capsaicin bound far away from the active site. Hydrogen bonds and π-stacking hydrophobic interactions are the main pancreatic lipase-polyphenolic compound interactions observed.

Modulation of PPAR Expression and Activity in Response to Polyphenolic Compounds in High Fat Diets.

Peroxisome proliferator-activated receptors (PPAR) are transcription factors that modulate energy metabolism in liver, adipose tissue and muscle. High fat diets (HFD) can negatively impact PPAR expression or activity, favoring obesity, dyslipidemia, insulin resistance and other conditions. However, polyphenols (PP) found in vegetable foodstuffs are capable of positively modulating this pathway. We therefore focused this review on the possible effects that PP can have on PPAR when administered together with HFD. We found that PP from diverse sources, such as coffee, olives, rice, berries and others, are capable of inducing the expression of genes involved in a decrease of adipose mass, liver and serum lipids and lipid biosynthesis in animal and cell models of HFD. Since cells or gut bacteria can transform PP into different metabolites, it is possible that a synergistic or antagonistic effect ultimately occurs. PP molecules from vegetable sources are an interesting option to maintain or return to a state of energy homeostasis, possibly due to an adequate PPAR expression and activity.

Inhibition of Urease by Disulfiram, an FDA-Approved Thiol Reagent Used in Humans.

Urease is a nickel-dependent amidohydrolase that catalyses the decomposition of urea into carbamate and ammonia, a reaction that constitutes an important source of nitrogen for bacteria, fungi and plants. It is recognized as a potential antimicrobial target with an impact on medicine, agriculture, and the environment. The list of possible urease inhibitors is continuously increasing, with a special interest in those that interact with and block the flexible active site flap. We show that disulfiram inhibits urease in Citrullus vulgaris (CVU), following a non-competitive mechanism, and may be one of this kind of inhibitors. Disulfiram is a well-known thiol reagent that has been approved by the FDA for treatment of chronic alcoholism. We also found that other thiol reactive compounds (l-captopril and Bithionol) and quercetin inhibits CVU. These inhibitors protect the enzyme against its full inactivation by the thiol-specific reagent Aldrithiol (2,2'-dipyridyl disulphide, DPS), suggesting that the three drugs bind to the same subsite. Enzyme kinetics, competing inhibition experiments, auto-fluorescence binding experiments, and docking suggest that the disulfiram reactive site is Cys592, which has been proposed as a "hinge" located in the flexible active site flap. This study presents the basis for the use of disulfiram as one potential inhibitor to control urease activity.

Cyanidin-3-O-glucoside: Physical-Chemistry, Foodomics and Health Effects.

Anthocyanins (ACNs) are plant secondary metabolites from the flavonoid family. Red to blue fruits are major dietary sources of ACNs (up to 1 g/100 g FW), being cyanidin-3-O-glucoside (Cy3G) one of the most widely distributed. Cy3G confers a red hue to fruits, but its content in raspberries and strawberries is low. It has a good radical scavenging capacity (RSC) against superoxide but not hydroxyl radicals, and its oxidative potential is pH-dependent (58 mV/pH unit). After intake, Cy3G can be metabolized (phases I, II) by oral epithelial cells, absorbed by the gastric epithelium (1%-10%) and it is gut-transformed (phase II & microbial metabolism), reaching the bloodstream (<1%) and urine (about 0.02%) in low amounts. In humans and Caco-2 cells, Cy3G's major metabolites are protocatechuic acid and phloroglucinaldehyde which are also subjected to entero-hepatic recycling, although caffeic acid and peonidin-3-glucoside seem to be strictly produced in the large bowel and renal tissues. Solid evidence supports Cy3G's bioactivity as DNA-RSC, gastro protective, anti-inflammatory, anti-thrombotic chemo-preventive and as an epigenetic factor, exerting protection against Helicobacter pylori infection, age-related diseases, type 2 diabetes, cardiovascular disease, metabolic syndrome and oral cancer. Most relevant mechanisms include RSC, epigenetic action, competitive protein-binding and enzyme inhibition. These and other novel aspects on Cy3G's physical-chemistry, foodomics, and health effects are discussed.

Phenolic profile, cheminformatics, and antiplatelet aggregation activity of orange and purple sweet potato (Ipomoea batatas L.) storage roots.

Sweet potatoes are rich in cardioprotective phytochemicals with potential anti-platelet aggregation activity, although this benefit may vary among cultivars/genotypes. The phenolic profile [HPLC-ESI(-)-qTOF-MS2], cheminformatics (ADMET properties, affinity toward platelet proteins) and anti-PA activity of phenolic-rich hydroalcoholic extracts obtained from orange (OSP) and purple (PSP) sweet potato storage roots, was evaluated. The phenolic richness [Hydroxycinnamic acids> flavonoids> benzoic acids] was PSP > OSP. Their main chlorogenic acids could interact with platelet proteins (integrins/adhesins, kinases/metalloenzymes) but their bioavailability could be poor. Just OSP exhibited a dose-dependent anti-platelet aggregation activity [inductor (IC50, mg.ml-1): thrombin receptor activator peptide-6 (0.55) > Adenosine-5'-diphosphate (1.02) > collagen (1.56)] and reduced P-selectin expression (0.75-1.0 mg.ml-1) but not glycoprotein IIb/IIIa secretion. The explored anti-PA activity of OSP/PSP seems to be inversely related to their phenolic richness. The poor first-pass bioavailability of its chlorogenic acids (documented in silico) may represent a further obstacle for their anti-PA in vivo.

Structural Stability and Viability of Microencapsulated Probiotic Bacteria: A Review.

Probiotics are live microorganisms that confer a number of health benefits when consumed in adequate amounts, mostly due to improvement of intestinal microflora. Bacterial strains from the genera Lactobacillus, Bifidobacterium, and Bacillus have been widely studied and are used to prepare ready-to-eat foods. However, the physicochemical stability and bioavailability of these bacteria have represented a challenge for many years, particularly in nonrefrigerated foodstuffs. Microencapsulation (ME) helps to improve the survival of these bacteria because it protects them from harsh conditions, such as high temperature, pH, or salinity, during the preparation of a final food product and its gastrointestinal passage. The most common coating materials used in the ME of probiotics are ionic polysaccharides, microbial exopolysaccharides, and milk proteins, which exhibit different physicochemical features as well as mucoadhesion. Structurally, the survival of improved bacteria depends on the quantity and strength of the functional groups located in the bacterial cell walls, coating materials, and cross-linkers. However, studies addressing the role of these interacting groups and the resulting metabolic impacts are still scarce. The fate of new probiotic-based products for the 21st century depends on the correct selection of the bacterial strain, coating material, preparation technique, and food vehicle, which are all briefly reviewed in this article.

Enriched Red Wine: Phenolic Profile, Sensory Evaluation and In Vitro Bioaccessibility of Phenolic Compounds.

The beneficial health effect of red wine depends on its phenolic content and the phenolic content in red wines is affected by ecological, agricultural, and enological practices. Enriched wines have been proposed as an alternative to increase the phenolic content in wines. Nevertheless, phenolic compounds are related to the sensory characteristics of red wines, so enrichment of red wines requires a balance between phenolic content and sensory characteristics. In the present study, a Merlot red wine was enriched with a phenolic extract obtained from Cabernet Sauvignon grape pomace. Two levels of enrichment were evaluated: 4 and 8 g/L of total phenolic content (gallic acid equivalents, GAE). Wines were evaluated by a trained panel to determine their sensory profile (olfactive, visual, taste, and mouthfeel phases). The bioaccessibility of phenolic compounds from enriched red wines was evaluated using an in vitro digestive model and phenolic compounds were quantified by High Performance Liquid Chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Enrichment increased mainly flavonols and procyanidins. Such an increase impacted astringency and sweetness perceived by judges. This study proposes an alternative to increase the phenolic content in wines without modifying other main sensory characteristics and offers a potential beneficial effect on the health of consumers.

Nanoparticle-Mediated Delivery of Flavonoids: Impact on Proinflammatory Cytokine Production: A Systematic Review.

Flavonoids are a diverse group of plant-derived compounds that have been shown to have various health benefits, including anti-inflammatory effects. However, their use in the treatment of inflammatory diseases has been limited due to their low bioavailability. The nanoparticle-mediated delivery of flavonoids has been proposed as a potential solution to this issue, as it allows the sustained release of the flavonoids over time. There are several different nanoparticle systems that have been developed for flavonoid delivery, including polymeric nanoparticles, liposomes, and inorganic nanoparticles. This systematic review aims to evaluate the impact of nanoparticle-mediated delivery of flavonoids on pro-inflammatory cytokine production in various diseases. We analyzed the performance of flavonoid-encapsulated nanoparticles in regulating cytokine production in different in vitro and in vivo studies. To this end, we followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to conduct a comprehensive search of the literature and to assess the quality of the included studies. The results showed that flavonoid-encapsulated nanoparticles significantly downregulated pro-inflammatory cytokines, such as TNF-α, IL-1ß, IL-6, and IL-18. In some cases, this effect was significantly greater than that observed with non-encapsulated flavonoids These findings suggest that nanoparticle-mediated delivery of flavonoids may have potential as a therapeutic approach for the treatment of inflammatory diseases.

Semi-Targeted Ultra-High-Performance Chromatography Coupled to Mass Spectrometry Analysis of Phenolic Metabolites in Plasma of Elderly Adults.

A group of 23 elderly persons was given functional meals (a beverage and a muffin) specially formulated for the prevention of sarcopenia (age-related loss of muscle mass). Plasma samples were taken at the beginning of the intervention and after 30 days of consuming the functional meals. A semi-targeted ultra-high-performance chromatography coupled with tandem mass (UPLC-MS/MS) analysis was carried out to identify phenolic compounds and their metabolites. Plasma proteins were precipitated with ethanol and the samples were concentrated and resuspended in the mobile phase (1:1 acetonitrile: water) before injection into the UPLC-MS/MS instrument. Separation was carried out with a C18 reverse-phase column, and compounds were identified using their experimental mass, isotopic distribution, and fragment pattern. Compounds of interest were compared to those of data banks and the internal semi-targeted library. Preliminary results showed that the major metabolites identified after the intervention were phenylacetic acid, glycitin, 3-hydroxyphenylvaleric acid, and gomisin M2.

In vitro gastrointestinal digestion and colonic fermentation of tomato (Solanum lycopersicum L.) and husk tomato (Physalis ixocarpa Brot.): Phenolic compounds released and bioconverted by gut microbiota.

Two of the most important Mexican plant-foods are tomato (Solanum lycopersicum L.) and husk tomato (Physalis ixocarpa Brot.). In this study three objectives were followed: i) to evaluate the bioaccessible phenolic compounds (PC) in T and HT during upper gastrointestinal digestion, ii) to in vitro ferment the indigestible fractions of the samples to evaluate the short-chain fatty acids (SCFA) production, iii) the microbial metabolites, bioconverted PC and volatile organic compounds (VOCs) generated during the fermentation. Vanillic acid was the most bioaccessible PC and after 48 h, 3-hydroxyphenylacetic acid was the most abundant microbial metabolite identified in both samples. The identification of VOCs belonging to terpenes (and derivatives) group in T and HT can be product of the microbial metabolism of carotenoids. The study shows new knowledge of the in vitro intestinal digestion and fermentation of T and HT final compounds with biological potential which should be evaluated in further studies.

Cardioprotective effect of red wine and grape pomace.

Several studies have related moderate consumption of red wine with prevention of cardiovascular diseases (CVD). According to epidemiological studies, those regions with high consumption of red wine and a Mediterranean diet show a low prevalence of CVD. Such an effect has been attributed to phenolic compounds present in red wines. On the other hand, by-products obtained during winemaking are also a significant source of phenolic compounds but have been otherwise overlooked. The cardioprotective effect of red wine and its byproducts is related to their ability to prevent platelet aggregation, modify the lipid profile, and promote vasorelaxation. Phenolic content and profile seem to play an important role in these beneficial effects. Inhibition of platelet aggregation is dose-dependent and more efficient against ADP. The antioxidant capacity of phenolic compounds from red wine and its by-products, is involved in preventing the generation of ROS and the modification of the lipid profile, to prevent LDL oxidation. Phenolic compounds can also, modulate the activity of specific enzymes to promote NO production and vasorelaxation. Specific phenolic compounds like resveratrol are related to promote NO, and quercetin to inhibit platelet aggregation. Nevertheless, concentration that causes those effects is far from that in red wines. Synergic and additive effects of a mix of phenolic compounds could explain the cardioprotective effects of red wine and its byproducts.

Functionality of Bread and Beverage Added with Brosimum alicastrum Sw. Seed Flour on the Nutritional and Health Status of the Elderly.

Physiological changes in elderly individuals (EI) can contribute to nutritional deterioration and comorbidities that reduce their quality of life. Factors such as diet can modulate some of these effects. The aim was to evaluate the functionality of foods added with Brosimum alicastrum Sw. seed flour in EI. EI (n = 23) living in nursing home conditions agreed to participate. A control stage was carried out (30 days) and subsequently, an intervention stage (30 days) was realized in which a muffin and a beverage, designed for EI, were added to the participants' their usual diet. In both stages, anthropometric parameters, body composition, nutritional status, dietary intake, sarcopenic status, cognitive and affective states, biometric parameters, and total phenolic compounds (TPC), and antioxidant capacity in foods and plasma of EI were determined. The results showed that the consumption of the foods improved the energy intake and preserved the muscle reserves of the EI. The EI gained body weight (+1.1 kg), increased their protein (+18.6 g/day; 1.5 g/kg BW/day), dietary fiber (+13.4 g/day), iron (+4.4 mg/day), zinc (+1.8 mg/day), folic acid (+83.4 µg/day) consumption while reducing their cholesterol (-66 mg/day) and sodium (-319.5 mg/day) consumption. LDL-C lipoproteins reduced (14.8%) and urea (33.1%) and BUN (33.3%) increased. The TPC increased (7.8%) in the plasma, particularly in women (10.7%). The foods improve the EI nutritional status, and this has a cardiovascular protective effect that can benefit the health of the EI.

Daily consumption of apple, pear and orange juice differently affects plasma lipids and antioxidant capacity of smoking and non-smoking adults.

Epidemiological studies have shown an inverse correlation between a fruit and vegetable-rich diet and cardiovascular diseases; this beneficial effect of fruits and vegetables is probably due to the presence of antioxidant phytochemicals. In contrast, cigarette smoking is a high risk factor for lung and heart diseases, associated with chronic oxidative stress. In the present study, the effect of the consumption of a pear, an apple and 200 ml orange juice, during 26 days, on total plasma antioxidant capacity (TAC) and lipid profile of chronic smokers and non-smoking healthy adults was analyzed. Fruit consumption increased TAC in non-smokers, but not in smokers. In non-smokers, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol increased significantly; while in smokers, total cholesterol and low-density lipoprotein-cholesterol decreased. We may conclude fruit/juice supplementation showed different effects, depending on the smoking habit: in non-smokers it increased TAC and cholesterol; in smokers it reduced cholesterol, without inducing a TAC increase.

Interaction of N-succinyl-diaminopimelate desuccinylase with flavonoids.

DapE is an enzyme that belongs to the meso-diaminopimelate/Lysine pathway. It is recognized as an antimicrobial target, hence compounds that inhibit its catalytic activity are required. The principal features considered in the selection of potential inhibitors for this enzyme are compounds containing metal binding groups that could block access of the substrate to the Zinc metal centers and/or block the assembly of the oxyanion hole. We show the interaction of DapE from Enterococcus faecium, Staphylococcus aureus, Klebsiella aerogenes, Pseudomonas aeruginosa and Escherichia coli with flavonoids: quercetin, catechin, luteolin, rutin and hesperidin. Flavonoids contain several oxygen atoms distributed along their structure in a pattern that may be considered for the development of new antibiotics. Docking experiments suggest that these compounds containing metal binding groups that interact with metal centers of DapE and binding experiments indicate that glycoside flavonoids are preferred by DapE.