Medicinal plants are rich sources of valuable molecules with various profitable biological effects, including antimicrobial activity. The advantages of herbal products are their effectiveness, relative safety based on research or extended traditional use, and accessibility without prescription. Extensive and irrational usage of antibiotics since their discovery in 1928 has led to the increasing expiration of their effectiveness due to antibacterial resistance. Now, medical research is facing a big and challenging mission to find effective and safe antimicrobial therapies to replace inactive drugs. Over the years, one of the research fields that remained the most available is the area of natural products: medicinal plants and their metabolites, which could serve as active substances to fight against microbes or be considered as models in drug design. This review presents selected flavonoids (such as apigenin, quercetin, kaempferol, kurarinone, and morin) and tannins (including oligomeric proanthocyanidins, gallotannins, ellagitannins, catechins, and epigallocatechin gallate), but also medicinal plants rich in these compounds as potential therapeutic agents in oral infectious diseases based on traditional usages such as Agrimonia eupatoria L., Hamamelis virginiana L., Matricaria chamomilla L., Vaccinium myrtillus L., Quercus robur L., Rosa gallica L., Rubus idaeus L., or Potentilla erecta (L.). Some of the presented compounds and extracts are already successfully used to maintain oral health, as the main or additive ingredient of toothpastes or mouthwashes. Others are promising for further research or future applications.
The aim of this work is to determine the biological activity of ellagitannins rich extracts from leaves of raspberry (Rubus idaeus L.) and wild strawberry (Fragaria vesca L.) in relation to cells and cell membranes. Detailed qualitative and quantitative analysis of phenolic compounds of the extract was made using chromatographic methods. Cytotoxic and antioxidant activities of tested extracts in relation to erythrocytes and human vascular endothelial cells (HMEC-1) were determined by using fluorimetric and spectrophotometric methods. In order to establish the influence of the extracts on the physical properties of the membrane, such as osmotic resistance and erythrocytes shapes, mobility and/or hydration of polar heads and fluidity of hydrocarbon chains of membrane lipids, microscopic and spectroscopic methods were used. The results showed that the extracts are non-toxic for erythrocytes and HMEC-1 cells (up to concentration of 50 μg/mL), but they effectively protect cells and their membranes against oxidative damage. The increase in osmotic resistance of erythrocytes, formation of echinocytes and changes only in the polar part of the membrane caused by the extracts demonstrate their location mainly in the hydrophilic part of the membrane. The results indicate that tested extracts have high biological activities and may be potentially used in delaying the ageing process of organisms and prevention of many diseases, especially those associated with oxidative stress.
- MeSH
- Antioxidants chemistry pharmacology MeSH
- Endothelial Cells MeSH
- Erythrocytes MeSH
- Hydrolyzable Tannins MeSH
- Fragaria * chemistry MeSH
- Humans MeSH
- Membrane Lipids MeSH
- Oxidative Stress MeSH
- Plant Extracts chemistry pharmacology MeSH
- Rubus * chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The aim of this publication is to compile a summary of the findings regarding punicalagin in various tissues described thus far in the literature, with an emphasis on the effect of this substance on immune reactions. Punicalagin (PUN) is an ellagitannin found in the peel of pomegranate (Punica granatum). It is a polyphenol with proven antioxidant, hepatoprotective, anti-atherosclerotic and chemopreventive activities, antiproliferative activity against tumor cells; it inhibits inflammatory pathways and the action of toxic substances, and is highly tolerated. This work describes the source, metabolism, functions and effects of punicalagin, its derivatives and metabolites. Furthermore, its anti-inflammatory and antioxidant effects are described.
- MeSH
- Anti-Inflammatory Agents pharmacology MeSH
- Biological Availability MeSH
- Hydrolyzable Tannins immunology metabolism MeSH
- Immunosuppressive Agents pharmacology MeSH
- Ellagic Acid analysis MeSH
- Humans MeSH
- Metabolome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
In Italy a particularly valuable chestnut is "Marrone di Roccadaspide", a protected geographical indication (PGI) product, deriving from a Castanea sativa cultivar, typical of Salerno province in Campania region. As chestnut industrial processes yield a large amount of shell by-products, in this study the possibility to retrain this waste food as potential source of bioactives was investigated. The ability of "Marrone di Roccadaspide" shell MeOH extract to modulate the pro-inflammatory transcriptional factor NF-κB after LPS stimulation, along with the antioxidant activity by a cell-based in vitro test, were evaluated. To correlate the NF-κB inhibition (67.67% at 5 μg/mL) and the strong antioxidant activity to the chemical composition, an analytical approach based on LC-ESI/LTQOrbitrap/MS/MSn along with NMR characterization of isolated compounds was developed. The identification of hydrolysable and condensed tannins, along with flavonoids, phenol glucosides, ellagic acid derivatives, and triterpenoids was accomplished. The most representative compounds were quantitatively analyzed by LC-ESI/QTrap/MS/MS, showing bartogenic acid as the compound occurring in the highest amount (103.08 mg/100 g shells). With the aim to explore the possibility to employ chestnut shells as suitable source of bioactives for the preparation of functional ingredients, the chemical composition and the antioxidant activity of "eco-friendly" extracts (EtOH and EtOH:H2O 7:3) was finally evaluated, showing a high superimposability of the EtOH:H2O (7:3) extract to the MeOH extract.
- MeSH
- Antioxidants analysis MeSH
- Fagaceae chemistry MeSH
- Phenols analysis MeSH
- Flavonoids analysis MeSH
- Glucosides analysis MeSH
- Evaluation Studies as Topic MeSH
- Hydrolyzable Tannins analysis MeSH
- Calibration MeSH
- Ellagic Acid analysis MeSH
- Humans MeSH
- NF-kappa B metabolism MeSH
- Nuts chemistry MeSH
- Proanthocyanidins analysis MeSH
- Cell Proliferation MeSH
- Rationalization * MeSH
- Reactive Oxygen Species MeSH
- Plant Extracts analysis MeSH
- Tandem Mass Spectrometry MeSH
- Tannins analysis MeSH
- Triterpenes analysis MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Italy MeSH
Mineralization of hydrogel biomaterials with calcium phosphate (CaP) is considered advantageous for bone regeneration. Mineralization can be both induced by the enzyme alkaline phosphatase (ALP) and promoted by calcium-binding biomolecules, such as plant-derived polyphenols. In this study, ALP-loaded gellan gum (GG) hydrogels were enriched with gallotannins, a subclass of polyphenols. Five preparations were compared, namely three tannic acids of differing molecular weight (MW), pentagalloyl glucose (PGG), and a gallotannin-rich extract from mango kernel (Mangifera indica L.). Certain gallotannin preparations promoted mineralization to a greater degree than others. The various gallotannin preparations bound differently to ALP and influenced the size of aggregates of ALP, which may be related to ability to promote mineralization. Human osteoblast-like Saos-2 cells grew in eluate from mineralized hydrogels. Gallotannin incorporation impeded cell growth on hydrogels and did not impart antibacterial activity. In conclusion, gallotannin incorporation aided mineralization but reduced cytocompatibility.
- MeSH
- Alkaline Phosphatase metabolism MeSH
- Anti-Bacterial Agents pharmacology MeSH
- Polysaccharides, Bacterial MeSH
- Biocompatible Materials MeSH
- Biomimetics methods MeSH
- Calcium Phosphates MeSH
- Calcification, Physiologic drug effects MeSH
- Hydrogels chemistry MeSH
- Hydrolyzable Tannins metabolism pharmacology MeSH
- Humans MeSH
- Mangifera chemistry MeSH
- Minerals chemistry MeSH
- Osteoblasts metabolism MeSH
- Polyphenols chemistry MeSH
- Polysaccharides chemistry MeSH
- Bone Regeneration MeSH
- Plant Extracts chemistry MeSH
- Plants metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Flavonoids are abundant polyphenols in nature. They are extensively biotransformed in enterocytes and hepatocytes, where conjugated (methyl, sulfate, and glucuronide) metabolites are formed. However, bacterial microflora in the human intestines also metabolize flavonoids, resulting in the production of smaller phenolic fragments (e.g., hydroxybenzoic, hydroxyacetic and hydroxycinnamic acids, and hydroxybenzenes). Despite the fact that several colonic metabolites appear in the circulation at high concentrations, we have only limited information regarding their pharmacodynamic effects and pharmacokinetic interactions. Therefore, in this in vitro study, we investigated the interactions of 24 microbial flavonoid metabolites with human serum albumin and cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes. Our results demonstrated that some metabolites (e.g., 2,4-dihydroxyacetophenone, pyrogallol, O-desmethylangolensin, and 2-hydroxy-4-methoxybenzoic acid) form stable complexes with albumin. However, the compounds tested did not considerably displace Site I and II marker drugs from albumin. All CYP isoforms examined were significantly inhibited by O-desmethylangolensin; nevertheless, only its effect on CYP2C9 seems to be relevant. Furthermore, resorcinol and phloroglucinol showed strong inhibitory effects on CYP3A4. Our results demonstrate that, besides flavonoid aglycones and their conjugated derivatives, some colonic metabolites are also able to interact with proteins involved in the pharmacokinetics of drugs.
- MeSH
- Erythrocytes enzymology MeSH
- Flavonoids * chemistry metabolism MeSH
- Hepatocytes enzymology MeSH
- Humans MeSH
- Serum Albumin, Human * chemistry metabolism MeSH
- Cytochrome P-450 Enzyme System * chemistry metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The structure of the carbohydrate moiety of a natural phenolic glycoside can have a significant effect on the molecular interactions and physicochemical and pharmacokinetic properties of the entire compound, which may include anti-inflammatory and anticancer activities. The enzyme 6-O-α-rhamnosyl-β-glucosidase (EC 3.2.1.168) has the capacity to transfer the rutinosyl moiety (6-O-α-l-rhamnopyranosyl-β-d-glucopyranose) from 7-O-rutinosylated flavonoids to hydroxylated organic compounds. This transglycosylation reaction was optimized using hydroquinone (HQ) and hesperidin as rutinose acceptor and donor, respectively. Since HQ undergoes oxidation in a neutral to alkaline aqueous environment, the transglycosylation process was carried out at pH values ≤6.0. The structure of 4-hydroxyphenyl-β-rutinoside was confirmed by NMR, that is, a single glycosylated product with a free hydroxyl group was formed. The highest yield of 4-hydroxyphenyl-β-rutinoside (38%, regarding hesperidin) was achieved in a 2-h process at pH 5.0 and 30 °C, with 36 mM OH-acceptor and 5% (v/v) cosolvent. Under the same conditions, the enzyme synthesized glycoconjugates of various phenolic compounds (phloroglucinol, resorcinol, pyrogallol, catechol), with yields between 12% and 28% and an apparent direct linear relationship between the yield and the pKa value of the aglycon. This work is a contribution to the development of convenient and sustainable processes for the glycosylation of small phenolic compounds.
SCOPE: Intake of flavonoids from the diet can be substantial, and epidemiological studies suggest that these compounds can decrease the incidence of cardiovascular diseases by involvement with increased platelet aggregation. Although parent flavonoids possess antiplatelet effects, the clinical importance is disputable due to their very low bioavailability. Most of them are metabolized by human colon bacteria to smaller phenolic compounds, which reach higher plasma concentrations than the parent flavonoids. In this study, a series of 29 known flavonoid metabolites is tested for antiplatelet potential. METHODS AND RESULTS: Four compounds appear to have a biologically relevant antiplatelet effect using whole human blood. 4-Methylcatechol (4-MC) is clearly the most efficient being about 10× times more active than clinically used acetylsalicylic acid. This ex vivo effect is also confirmed using a potentially novel in-vivo-like ex ovo hen's egg model of thrombosis, where 4-MC significantly increases the survival of the eggs. The mechanism of action is studied and it seems that it is mainly based on the influence on intracellular calcium signaling. CONCLUSION: This study shows that some flavonoid metabolites formed by human microflora have a strong antiplatelet effect. This information can help to explain the antiplatelet potential of orally given flavonoids.
- MeSH
- Platelet Aggregation drug effects MeSH
- Platelet Aggregation Inhibitors pharmacology MeSH
- Cyclooxygenase Inhibitors pharmacology MeSH
- Enzyme Inhibitors pharmacology MeSH
- Catechols pharmacology MeSH
- Chick Embryo MeSH
- Arachidonic Acid pharmacology MeSH
- Humans MeSH
- Drug Evaluation, Preclinical methods MeSH
- Pyrogallol pharmacology MeSH
- Serotonin metabolism MeSH
- Thromboxane-A Synthase antagonists & inhibitors MeSH
- Thrombosis drug therapy MeSH
- Animals MeSH
- Check Tag
- Chick Embryo MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Quercetin is an abundant flavonoid in nature and is used in several dietary supplements. Although quercetin is extensively metabolized by human enzymes and the colonic microflora, we have only few data regarding the pharmacokinetic interactions of its metabolites. Therefore, we investigated the interaction of human and microbial metabolites of quercetin with the xanthine oxidase enzyme. Inhibitory effects of five conjugates and 23 microbial metabolites were examined with 6-mercaptopurine and xanthine substrates (both at 5 μM), employing allopurinol as a positive control. Quercetin-3'-sulfate, isorhamnetin, tamarixetin, and pyrogallol proved to be strong inhibitors of xanthine oxidase. Sulfate and methyl conjugates were similarly strong inhibitors of both 6-mercaptopurine and xanthine oxidations (IC50 = 0.2-0.7 μM); however, pyrogallol inhibited xanthine oxidation (IC50 = 1.8 μM) with higher potency vs. 6-MP oxidation (IC50 = 10.1 μM). Sulfate and methyl conjugates were approximately ten-fold stronger inhibitors (IC50 = 0.2-0.6 μM) of 6-mercaptopurine oxidation than allopurinol (IC50 = 7.0 μM), and induced more potent inhibition compared to quercetin (IC50 = 1.4 μM). These observations highlight that some quercetin metabolites can exert similar or even a stronger inhibitory effect on xanthine oxidase than the parent compound, which may lead to the development of quercetin-drug interactions (e.g., with 6-mercaptopurin or azathioprine).
- MeSH
- Allopurinol chemistry pharmacology MeSH
- Enzyme Inhibitors chemistry metabolism pharmacology MeSH
- Catalysis MeSH
- Humans MeSH
- Molecular Conformation MeSH
- Models, Molecular MeSH
- Molecular Structure MeSH
- Oxidation-Reduction MeSH
- Quercetin analogs & derivatives chemistry metabolism pharmacology MeSH
- Protein Binding MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Xanthine chemistry pharmacology MeSH
- Xanthine Oxidase antagonists & inhibitors MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND AND AIM: Increased homocysteine (Hcy) is associated with coronary artery disease (CAD). Hcy increases reactive oxygen species (ROS) via NADPH oxidases (Nox), reducing acetylcholine-mediated vasorelaxation. We aimed to determine if putative Nox2 inhibitors prevent Hcy-impaired acetylcholine-mediated vasorelaxation. METHODS AND RESULTS: New Zealand White rabbit and wild-type (C57BL/6) and Nox2-/- (NOX) mice aortic rings were mounted in organ baths. Rabbit rings were incubated with either apocynin (10 μM), gp91ds-tat (GP, 1 μM) or PhoxI2 (1 μM) and mice rings GP (1 μM) only. Some rabbit rings were incubated with 3 mM Hcy, before pre-contraction, followed by dose-response relaxation to acetylcholine (ACh; 0.01μM-10μM). In rabbit rings treated with Hcy and GP, O2‾ donor pyrogallol (1 μM) or Akt activator SC79 (1 μM) was added 5 min before ACh. Mice rings were used to compare Nox2 deletion to normal acetylcholine-mediated relaxation. In rabbits, Hcy reduced acetylcholine-mediated relaxation vs. control (p < 0.0001). Treatment + Hcy reduced relaxation compared with treatment alone (p < 0.0001). Pyrogallol and SC79 reversed the response of GP + Hcy (p = 0.0001). In mice, Nox2 deletion reduced acetylcholine-mediated vasorelaxation. Rabbit tissue analysis revealed that Hcy reduced eNOS phosphorylation at Thr495 and increased eNOS phosphorylation at Ser1177; no further alteration at Thr495 was observed with GP. In contrast, GP prevented increased phosphorylation at Ser1177. CONCLUSIONS: Apocynin, GP and PhoxI2 worsens acetylcholine-mediated vascular relaxation in rabbit aorta, which is supported by results from mouse Nox2 deletion data. These inhibitors worsen Hcy-induced vascular dysfunction, suggesting that current putative Nox2 inhibitors might not be useful in treating HHcy.
- MeSH
- Acetophenones pharmacology MeSH
- Acetylcholine pharmacology MeSH
- Aorta drug effects enzymology MeSH
- Phosphorylation MeSH
- Glycoproteins pharmacology MeSH
- Homocysteine pharmacology MeSH
- Enzyme Inhibitors pharmacology MeSH
- Rabbits MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout MeSH
- NADPH Oxidase 2 antagonists & inhibitors genetics metabolism MeSH
- Serine MeSH
- Nitric Oxide Synthase Type III metabolism MeSH
- In Vitro Techniques MeSH
- Threonine MeSH
- Vasodilation drug effects MeSH
- Vasodilator Agents pharmacology MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
