Onion quercetin monoglycosides alter microbial activity and increase antioxidant capacity

The effects on fermentation processes in the digestive tract, the biochemical parameters and antioxidant capacity of blood in rats fed high-fat diets with quercetin (Q) and quercetin with quercetin monoglycosides (Q+MQ) preparations obtained from onion waste were evaluated. Four groups of eight animals were fed for 4 weeks with a control diet (C), a high-fat diet (HF) and high-fat diets with 0.15% addition of Q and Q+MQ preparations. HF caused an increase in alanine transaminase (ALT), non-high-density lipoprotein (non-HDL) and the atherogenic index AII vs. C and a decrease in the proportion of HDL in total cholesterol (TC). Q and Q+MQ showed a tendency to moderate the values aspartate transaminase (P=.087), ALT (P<.05), TC (P=.068), non-HDL cholesterol (P<.05), triglycerides (P=.064) and the atherogenic index AII (P<.05). Q+MQ significantly increased the activity of α-glucosidase (P<.05 vs. HF), β-glucosidase (P<.05) and β-galactosidase (P<.05 vs. C and Q). Q increased activity of β-glucosidase (P<.001 vs. C and HF). Both increased the activity of β-glucuronidase (P<.05 vs. C and HF). Both increased the antioxidant capacity of the hydrophilic fraction in serum (P<.05 vs. C and HF), and Q enhanced that of the lipid fraction (P<.001). Q preparation contained 70% quercetin, and Q+MQ preparation contained 29% quercetin and 13% quercetin monoglycosides, mainly quercetin-4’-glucoside. Both exhibited high antioxidant capacity. Supplementation with Q and Q+MQ increased the enzymatic activity of the intestinal microbiota and the antioxidant capacity of blood and revealed a tendency to improve the blood lipid profile. MQ were particularly effective in stimulating the bacterial enzymatic activity.     

Antimutagenic effect of an antioxidant in mammals

To test a possible antimutagenic activity of ethoxyquin (EQ) in bone-marrow cells, 3 cytogenetic tests with distinct genetic end-points were applied. Cyclophosphamide (CPA), serving as test mutagen, and the antioxidant EQ were administered immediately following each other to Chinese hamsters by stomach tube. Whereas the CPA dose was the same in each test, the EQ doses were increased up to a ratio of CPA/EQ = 1:25, in some cases up to 1:50. The formation of SCEs induced by CPA was not influenced by EQ--even at the highest dose. In the micronucleus test, however, EQ drastically reduced the micronucleus rate even at the lowest dose applied (20 mg/kg) and abolished the CPA effects at a dose of 100 mg/kg. This action of EQ against CPA was also found in the rat and mouse in the micronucleus test system. Two inbred strains of mouse showed similar reactions, but the induced micronucleus rate was higher and its decrease in response to increasing doses of EQ was more delayed. In the chromosome aberration test, EQ also showed a distinct anticlastogenic response. At higher EQ doses, all CPA-induced chromosomal damage was reduced down to the level of spontaneous rates. The anticlastogenic effect of EQ was quantitatively similar in the micronucleus and chromosome aberration tests. Only minor qualitative differences were recognizable.     

UV Rays, the prooxidant/antioxidant imbalance in the cornea and oxidative eye damage

In this minireview, the factors involved in the development of corneal injury due to an increased amount of UVB rays are summarized. Experimental studies have shown that an increased number of UVB rays leads to a profound decrease in corneal antioxidants (high molecular weight, antioxidant enzymes as well as low molecular weight, mainly ascorbic acid) so that a prooxidant/antioxidant imbalance appears. The decrease of corneal antioxidant protective mechanisms results in oxidative injury of the cornea and causes damage of the inner parts of the eye by UVB rays and by reactive oxygen species generated by them.     

Antimutagenic and anticarcinogenic activity of tea polyphenols

Tea is the most popular beverage, consumed by over two thirds of the world's population. Tea is processed differently in different parts of the world to give green (20%), black (78%) or oolong tea (2%). Green tea is consumed mostly in Japan and China. The antimutagenic and anticarcinogenic activities of green tea are extensively examined. The chemical components of green and black tea are polyphenols, which include EC, ECG, EGC, EGCG and TFs. This article reviews the epidemiological and experimental studies on the antimutagenicity and anticarcinogenicity of tea extracts and tea polyphenols. In Japan, an epidemiological study showed an inverse relationship between habitual green tea drinking and the standardized mortality rates for cancer. Some cohort studies on Chanoyu (Japanese tea ceremony) women teachers also showed that their mortality ratio including deaths caused by malignant neoplasms were surprisingly low. The antimutagenic activity against various mutagens of tea extracts and polyphenols including ECG and EGCG has been demonstrated in microbial systems (Salmonella typhimurium and Escherichia coli), mammalian cell systems and in vivo animal tests. The anticarcinogenic activity of tea phenols has been shown in experimental animals such as rats and mice, in transplantable tumors, carcinogen-induced tumors in digestive organs, mammary glands, hepatocarcinomas, lung cancers, skin tumors, leukemia, tumor promotion and metastasis. The mechanisms of antimutagenesis and anticarcinogenesis of tea polyphenols suggest that the inhibition of tumors may be due to both extracellular and intracellular mechanisms including the modulation of metabolism, blocking or suppression, modulation of DNA replication and repair effects, promotion, inhibition of invasion and metastasis, and induction of novel mechanisms.     

Antimutagenic activity of green tea polyphenols

For centuries green tea has been a widely consumed beverage throughout the world. It is known to contain a number of pharmacologically active compounds. In this study water extracts of green tea (WEGT) and their major constituents, green tea polyphenols (GTP), were examined for antimutagenic activity. WEGT and GTP were found to significantly inhibit the reverse mutation induced by benzo[alpha]pyrene (BP), aflatoxin B1 (AFB1), 2-aminofluorene, and methanol extracts of coal tar pitch in Salmonella typhimurium TA100 and/or TA98 in the presence of a rat-liver microsomal activation system. GTP also inhibited gene forward mutation in V79 cells treated with AFB1 and BP, and also decreased the frequency of sister-chromatid exchanges and chromosomal aberrations in V79 cells treated with AFB1. The addition of GTP during and after nitrosation of methylurea resulted in a dose-dependent inhibition of mutagenicity. Studies to define the mechanism of the antimutagenic activity of GTP suggest that it may affect carcinogen metabolism, DNA adduct formation, the interaction of ultimate carcinogen or the scavenging of free radicals.     

Antimutagenic activity of wheat beta-purothionin Tk-AMP-BP

Antimutagenic activity on human RD cells was studied for beta-purothionin Tk-AMP-BP isolated from seeds of wheat Triticum kiharae, which has a higher stress resistance. Cadmium chloride at 5 x 10(-6) M was used as a mutagen. The numbers of DNA breaks in mutagen-treated and intact cells were inferred from the single-stranded to double-stranded DNA ratio and expressed as protection coefficients. The protective effect was simultaneously assayed for aqueous plant extracts known to possess antioxidant properties. Wheat thionin was the most active among all of the antimutagens examined; its protection coefficient reached 85-88% at micromolar peptide concentrations (8-32 microg/ml). Thus, wheat beta-purothionin was for the first time demonstrated to be highly efficient in protecting human cell DNA from the damaging effect of cadmium chloride.     

Mechanisms of antioxidant activities of quercetin and catechin

Abstract

The seleno-organic compound ebselen mimics the glutathione-dependent, hydroperoxide reducing activity of glutathione peroxidase. The activity of glutathione peroxidase determines the rate of hydroperoxide-induced Ca²⁺ release from mitochondria. Ebselen stimulates Ca²⁺ release from mitochondria, accelerates mitochondrial respiration and uncoupling, and induces mitochondrial swelling, indicating a deterioration of mitochondrial function. These manifestations are abolished by cyclo-sporine A, a potent inhibitor of the mitochondrial permeability transition. However, when ebselen-induced Ca²⁺ cycling is prevented with ruthenium red, an inhibitor of the Ca²⁺ uniporter, or by chelation of extramitochondrial Ca²⁺ by EGTA, no detectable elevation of swelling or uncoupling is observed. The release of Ca²⁺ from mitochondria is delayed in the absence of rotenone, i.e. when pyridine nucleotides are maintained in the reduced state due to succinate-driven reversed electron flow. We suggest that ebselen induces Ca²⁺ release from intact mitochondria via an NAD⁺ hydrolysis-dependent mechanism.     

Antimutagenic activity of mitochondria-targeted plastoquinone derivative

The ability of cationic plastoquinone derivative 10-(6′-plastoquinonyl) decyltriphenylphosphonium (SkQ1) to modify processes of spontaneous and induced mutagenesis was studied. It is shown that daily introduction of this compound into male Wistar rats in doses of 25 and 250 nmol/kg during two weeks decreases spontaneous level of chromosome aberrations in anaphase in the eye cornea from 0.39 ± 0.09 to 0.13 ± 0.08 and 0.14 ± 0.05, respectively. The level of 8-hydroxy-2′-deoxyguanosine in blood serum of the investigated animals decreases from 32.12 ± 1.55 to 25.90 ± 2.26 and 25.76 ± 1.50 ng/ml, respectively. These facts indicate that the decrease in spontaneous clastogenesis is caused by decreased level of DNA damage by endogenous reactive oxygen species. A higher dose of SkQ1 also decreases to control level chromosome aberrations caused by oxygen under pressure of 0.5 MPa for 60 min. It is also shown in experiments with bacterial biosensors that SkQ1 is able to efficiently protect cells against genotoxic effect of UV radiation at 300–400 nm.     

Modulation of arachidonic acid metabolism by phenols: relation to their structure and antioxidant/prooxidant properties

The effects of substituted catechols (3-methylcatechol, 4-methylcatechol, 4-nitrocatechol, and guaiacol) and trihydroxybenzenes (pyrogallol, propyl gallate, 1,2,4-trihydroxybenzene, and 1,3,5-trihydroxybenzene) on the synthesis of prostaglandin (PG)E₂ and leukotriene (LT)B₄ were tested in human A23187-stimulated polymorphonuclear leukocytes. The effects were related to their peroxyl-radical-scavenging (antioxidant), superoxide-scavenging (antioxidant), and superoxide-generating (prooxidant) properties. In general, compounds with hydroxyl groups in the ortho position increased PGE₂/LTB₄ ratio, and compounds with hydroxyl groups in the meta position decreased PGE₂/LTB₄ ratio. Catechols, which have hydroxyl groups in the ortho position, were the most potent peroxyl radical and superoxide anion scavengers. Trihydroxybenzenes (pyrogallol, 1,2,4-trihydroxybenzene, and 1,3,5-trihydroxybenzene) generated superoxide, whereas dihydroxybenzenes did not. Thus, the positions and number of hydroxyl groups seem to be the most important properties determining the action of phenolic compounds on PGE₂/LTB₄ ratio and their antioxidant/prooxidant activities.     

Antimutagenic activity of new analogues of fluphenazine

Fluphenazine (FPh) exhibited antimutagenic activity in lymphocyte cultures, markedly decreasing genotoxic effects of standard mutagenic agents present in cell cultures. However, the strong pharmacological activity of this neuroleptic drug, together with its serious side effects on the central nervous system, limits its use as an antimutagenic compound. In this paper we describe a route of chemical synthesis of FPh analogues that are more hydrophilic than the model compound, thus probably penetrate more weakly through the blood-brain barrier. These new analogues were tested for their antimutagenic and pro-apoptotic activities in human lymphocyte cultures, genotoxically damaged in vitro with benzo[a]pyrene [40 microM, 30 min] and subsequently cultured for 48 h in the presence of the tested compounds. The fluphenazine analogues enhanced apoptosis in genotoxically damaged lymphocytes more strongly than the model compound did. The increase of apoptotic cell frequency was the highest with compound 4a [2-(trifluoromethyl)-10-[3-(diethanolamino)-2-hydroxypropyl] phenothiazine]--a 35% higher effect than that of fluphenazine. The cytotoxicity of derivative 4a was the lowest among the tested compounds; it was 60% lower than that of fluphenazine. The antimutagenic effect of 4a was about 10% stronger than that of fluphenazine. Compound 4a also had the highest hydrophilicity of the new FPh analogues. Compound 4a was chosen for further study as a potentially usable antimutagen that would only weakly penetrate the central nervous system.     

Lipid antioxidant properties of quercetin in vitro

The effect of quercetin on iron-catalyzed hepatic microsomal lipid peroxidation was investigated. Quercetin was shown to be a potent inhibitor of iron-induced lipid peroxidation with a I50 of 0.2 mM. The inhibitory effects of quercetin were dependent on incubation time, protein concentration and iron content in the incubation mixture. Since quercetin does not interact with malonyl-aldehyde it can be concluded that the inhibition of iron induced lipid peroxidation is due to lipid antioxidant property and this may serve as a model for the study by which "free" iron may initiate peroxidation in vivo.     

Antimutagenic activity of dextran gammaphos derivatives]

In experiments with V-79 Chinese hamster cell culture the influence of dextran gammaphos derivatives on the mutagenic effects of gamma-radiation was studied by the number of cells with micronuclei and fragmented nuclei. Products of interaction between gammaphos and dialdehyde dextran were shown to have a higher antimutagenic activity than gammaphos.     

Antimutagenic activity of soybeans fermented with basidiomycetes in Ames/Salmonella test

Soybeans fermented with either Phellinus igniarius or Agrocybe cylindracea inhibited the mutagenicity of the directly-acting mutagens: 4-nitro-o-phenylenediamine on Salmonella typhimurium strain TA 98 and NaN₃ on S. typhimurium strain TA 100; and indirectly-acting mutagens, 2-aminofluorene using strain TA 98 and benzo[a]pyrene using strain TA 100, in the presence of a supernatant solution from mammalian hepatic microsomes.     

Antimutagenic activity of flavonoids from Chrysanthemum morifolium

A methanol extract from the flower heads of Chrysanthemum morifolium showed a suppressive effect on umu gene expression of the SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide). The methanol extract was re-extracted with hexane, chloroform, ethyl acetate, butanol, and water. The ethyl acetate fraction showed a suppressive effect. Suppressive compounds in the ethyl acetate fraction were isolated by silica gel column chromatography and identified as the flavonoids acacetin (1), apigenin (2), luteolin (3), and quercetin (4) by EI-MS, IR, and (1)H and 13C NMR spectroscopy. Compounds 1-4 suppressed the furylfuramide-induced SOS response in the umu test. Compounds 1-4 suppressed 60.2, 75.7, 90.0, and 66.6% of the SOS-inducing activity at a concentration of 0.70 micromol/ml. The ID50 (50% inhibitory dose) values of 1-4 were 0.62, 0.55, 0.44, and 0.59 micromol/ml. These compounds had the suppressive effects on umu gene expression of the SOS response against other mutagens, 4-nitroquinolin 1-oxide (4NQO) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which do not require liver-metabolizing enzymes. These compounds also showed the suppression of SOS-inducing activity against the other mutagens aflatoxin B1 (AfB1) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which require liver-metabolizing enzymes, and UV irradiation. In addition to the antimutagenic activities of these compounds against furylfuramide, Trp-P-1 and activated Trp-P-1 were also assayed by the Ames test using S. typhimurium TA100.     

The nature of prooxidant activity of vitamin C.

It was recently reported that vitamin C (500 mg/day for 6 weeks) administered as a dietary supplement to healthy humans exhibits a prooxidant, as well as an antioxidant effect in vivo. Here we show that high intakes of vitamin C (500 mg/kg b.w. for 4 days) in the rat are able to markedly induce hepatic cytochrome P4502E1-linked monooxygenases, measured as p-nitrophenol hydroxylase activity and corroborated by means of Western blot analyses. Furthermore, using Electron Paramagnetic Resonance Spectroscopy (EPR) coupled to a spin-trapping technique, we have also found that this induction generates large amounts of the anion radical superoxide (O2-). Therefore we can conclude that the adverse prooxidant outcomes (i.e. oxidative DNA damage) associated to vitamin C supplementation, being associated to a typical reversible boosting effect (i.e. enzymatic induction), may be easily controlled by a discontinuous supply. However, since the induced P4502E1 isoforms by vitamin C are responsible for ethanol metabolism to highly reactive radicals, care should be taken even in moderate drinkers.