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PubMedDate not supplied

Clara cell 10-KDA protein inhibits endotoxin-induced airway contraction in isolated perfused rat lungs.

Clara cell 10-kDa protein (CC10) is a major component of bronchoalveolar lavage fluid and is suggested to be a natural regulator of airway inflammation, possibly through its effects on the proinflammatory enzyme(s), phospholipase A2. We examined the effect of recombinant human (rh) CC10 on endotoxin-induced airway contraction and cytokine release in isolated perfused rat lungs. We found that rhCC10 added to the lung perfusate abolished the endotoxin-induced airway contraction, and that it inhibited both the release of interleukin-1 beta and interleukin-6 into the lung perfusate and the release of tumor necrosis factor-alpha into the pulmonary lavage fluid. By contrast, the levels of interferon-gamma were unaffected by CC10 administration. Rutin, a phospholipase A2 inhibitor, and N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, also attenuated the contraction induced by endotoxin. These findings demonstrate that rhCC10 inhibits endotoxin-induced airway contraction and the release of proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) in isolated perfused rat lungs. The results also indicate that phospholipase A2 and nitric oxide are involved in the airway contraction in this model, possibly through their influence on the production of eicosanoids.

Acetylcholine↗

PubMed2003

The study of phenolic compounds as natural antioxidants in wine.

Plant phenolics present in fruit and vegetables, and that are particularly rich in red wine, have received considerable attention because of their potential antioxidant activity. Human consumption of antioxidants has many alleged health benefits, including protection against cardiovascular diseases, and, most recently, cancer. Red wines contain a variety of polyphenolic antioxidants. Five samples of commercial red wines from Spain and four phenolic compounds of red wine: gallic acid, trans-resveratrol, quercetin and rutin, have been studied. The total phenolics content and the total antioxidant activity (TAA) of wines was determined. The total phenolic content, determined according to the Folin-Ciocalteu method, varied from 1800 to 2300 mg/L, expressed as gallic acid equivalents (GAE). The antioxidative effects of wine phenolics were determined using a system based on the inhibition by antioxidants of the absorbance of the radical cation. The relationship between antioxidant activity of phenolic comounds, as hydrogen donating free radical scavengers, and their chemical structures was studied. Furthermore, the total antioxidant activity of the wines investigated was well correlated with phenol content. Thus, the results confirm that red wine polyphenols are, in vitro, significant antioxidants.

Antioxidants↗

PubMed2001

Redox reactions of the urate radical/urate couple with the superoxide radical anion, the tryptophan neutral radical and selected flavonoids in neutral aqueous solutions.

The kinetics of several processes involving the potential antioxidant role of urate in physiological systems have been investigated by pulse radiolysis. While the monoanionic urate radical, .UH-, can be produced directly by oxidation with .Br2- or .OH, it can also be generated by oxidation with the neutral tryptophan radical, .Trp, with a rate constant of 2 x 10(7) M-1s-1. This radical, .UH-, reacts with .O2- with a rate constant of 8 x 10(8) M-1s-1. Also, .UH- is reduced by flavonoids, quercetin and rutin in CTAB micelles at rate constants of 6 x 10(6) M-1s-1 and 1 x 10(6) M-1s-1, respectively. These results can be of value by providing reference data useful in further investigation of the antioxidant character of urate in more complex biological systems.

Animals↗

PubMed2002

Down-regulation of antioxidative capacity in a transgenic tobacco which fails to develop acquired resistance to necrotization caused by TMV.

Antioxidant status was assayed in leaves of two local lesion hosts of tobacco mosaic virus (TMV), namely in wild-type Xanthi-nc tobacco and in NahG transgenic tobacco, the latter of which is not able to accumulate salicylic acid (SA) and therefore is unable to develop systemic acquired resistance (SAR). Activities of several enzymes related to antioxidative defense, and the levels of glutathione, chlorogenic acid and rutin were studied. The majority of antioxidant enzymes were less active in uninfected NahG tobacco than in Xanthi-nc. Furthermore, important enzymatic and non-enzymatic antioxidants were down-regulated in TMV-infected NahG plants, as compared to Xanthi-nc. Correspondingly, SA pretreatment primed the leaves for stronger induction of antioxidants in infected Xanthi-nc, but not in NahG tobaccos. The antioxidant status of NahG tobacco even decreased after an attempted induction of SAR, while the antioxidative level increased in Xanthi-nc leaves in which the SAR was successfully induced. After infection, a greater accumulation of superoxide and H2O2, and a more intensive necrotization was positively correlated with the reduced capability of NahG leaf tissue to detoxify reactive oxygen species.

Antioxidants↗

PubMed1999

The polyphenolic content of fruit and vegetables and their antioxidant activities. What does a serving constitute?

Analysis of the major flavone, flavonol, anthocyanidin and hydroxycinnamic acid constituents (and their glycosides) of onion, tomato, egg plant and apple has been undertaken and the antioxidant activities of the phenolic extracts determined. The major phenolic antioxidant components of egg plant are chlorogenic acid in the flesh and a delphinidin conjugate in the skin. In the case of apple, the major phenolic antioxidants detected are chlorogenic acid, procyanidins/catechin compounds, rutin and phloridzin. Quercetin glycosides are well-known to be the major phenolic components of onion. Assessment of the antioxidant activities of a serving of 100g fresh weight fruit, vegetable and comparison with previously reported findings for 150 ml beverage (500 ml portion in the case of beer), expressed in micromol Trolox equivalents show that the antioxidant activities of 1 glass (150 ml) red wine equivalent to 12 glasses white wine equivalent to 2 cups of tea equivalent to 4 apples equivalent to 5 portions of onion equivalent to 5.5 portions egg plant equivalent to 3.5 glasses of blackcurrant juice equivalent to 3.5 (500 ml) glasses of beer equivalent to 7 glasses of orange juice equivalent to 20 glasses of apple juice (long life).

Anthocyanins↗

PubMed2004

Constituents from leaves of Quillaja brasiliensis.

A new abietane diterpene, the 19-O-beta-D-glucopyranoside of 16-hydroxylambertic acid was isolated from the leaves of Quillaja brasiliensis together with a known prosapogenin (3-O-beta-D-glucuronopyranosyl-quillaic acid), quercetin, and rutin. The new compound was identified by chemical and spectroscopic methods.

Glucosides↗

PubMed2005

Comparative chemical composition and variability of biological activity of methanolic extracts from Hypericum perforatum L.

The biovariability of Hypericum perforatum L. (St. John's Wort) grown wild in Calabria and Sardinia (Italy) was reported with the aim to characterize the species through the isolation, detection, and quantitative evaluations of chemical markers (hypericin, quercetin, rutin) by HPLC analysis. Antioxidant activity of the methanolic H. perforatum extracts showed that the Calabrian samples were more active than those from Sardinia. The antibacterial activity evidenced the best performance on the gram positive bacteria with a MIC value of 50 microg/mL. Moreover, antifungal activity of all the extracts was also tested which showed interesting results particularly on the phytopathogene fungus P. ultimum. The variability shown by the samples could be attributed to environmental factors such as chemical-physical properties, composition of the soil, geographical coordinate, altitude, and solar exposure. The phytochemical analysis and the biological activity data suggested a possible use of H. perforatum extracts in the alimentary, cosmetic, and pharmaceutical fields.

Anthracenes↗

PubMed1997

Rutoxyl [rutin/4-acetamide-1-hydroxy-2,2,6,6-tetramethylpiperidinium] is a new member of the class of semi-natural products of high pharmacological potency.

A novel complex, Rutoxyl [rutin/4-acetamide-1-hydroxy-2,2,6,6-tetramethylpiperidinium] was synthesized and its structure and anticancer activity were investigated. The results reported here are consistent with our idea, that the formation of such a complex of two biologically active molecules: polyphenolic flavonoid antioxidant (Rutin) and nitroxylamine of nitroxide antioxidant (Tempace), stabilized by hydrogen bond(s) can result in a supra-additive properties.

Animals↗

PubMed1999

Different effects of the constituents of EGb761 on apoptosis in rat cerebellar granule cells induced by hydroxyl radicals.

The present study was conducted to evaluate the different effects of the constituents of EGb761 (Ginkgo biloba Extract) on apoptosis in cerebellar granule cells induced by hydroxyl radicals. The total flavonoid component of EGb761, two pure EGb761 components (rutin and quercetin), and a mixture of flavonoids and terpenes protected cerebellar granule cells from oxidative damage and apoptosis induced by hydroxyl radicals. ESR(electron spin resonance) results showed that the IC50 of the flavonoids for scavenging hydroxyl radicals was almost the same as that of EGb761, even though flavonoids make up only 24% of EGb761, implying that other constituents of EGb761 besides flavonoids can scavenge hydroxyl radicals. Total terpenes of EGb761 did not protect against apoptosis. Flavonoids and terpenes did not show a synergistic effect in this regard. Terpenes did not scavenge hydroxyl radicals directly, which might be related to their "cage-like" structures.

Animals↗

PubMed1980

Induction of acute cholecystitis by activation of factor XII.

Acute, acalculous cholecystitis is seen among patients suffering with bacterial sepsis, burns, trauma, or cancer; clinical conditions that could lead to activation of factor XII-dependent pathways and result in inflammation of the gall bladder. To test this hypothesis, dogs were injected intravenously with ellagic acid or rutin, known polyphenol activators of factor XII, or with Escherichia coli endotoxin, also known to activate factor XII, and monkeys were injected intravenously with ellagic acid. In both species, in vivo activation of factor XII-dependent pathways with polyphenol activator resulted in rapid and selective development of acute vasculitis in the serosa and muscularis of the gallbladder and margination of polymorphonuclear neutrophils in pulmonary blood vessels. Intravenous injection of E. coli endotoxin in dogs resulted in necrosis and thrombosis of vessels that were especially severe in the serosa and muscularis of the gallbladder but also present in vessels of many other organs. These observations indicate that blood vessels of the gall bladder and, to a lesser degree, the lung are especially sensitive to injury consequent to in vivo activation of factor XII-dependent pathways and, in view of the common ingestion of plant polyphenols, may provide important insight into the pathogenesis of cholecystitis in man.

Animals↗

PubMed2003

Meat and cancer: haemoglobin and haemin in a low-calcium diet promote colorectal carcinogenesis at the aberrant crypt stage in rats.

High intake of red meat, but not of white meat, is associated with an increased risk of colon cancer. However, red meat does not promote cancer in rodents. Haemin, added to low-calcium diets, increases colonic proliferation, and haemoglobin, added to high-fat diets, increases the colon tumour incidence in rats, an effect possibly due to peroxyl radicals. We thus speculated that haem might be the promoting agent in meat, and that prevention strategies could use calcium and antioxidants. These hypotheses were tested in rats at the aberrant crypt foci (ACF) stage at 100 days. F344 rats (n = 124) were given an injection of azoxymethane and were then randomized to 11 groups fed with low-calcium (20 micro mol/g) AIN76-based diets, containing 5% safflower oil. Haemin (0.25, 0.5 and 1.5 micro mol/g) or haemoglobin (1.5 and 3 micro mol haem/g) was added to five experimental diets, compared with a control diet without haem. Three other high-haemin diets (1.5 micro mol/g) were supplemented with calcium (250 micro mol/g), antioxidant butylated hydroxyanisole and rutin (0.05% each), and olive oil, which replaced safflower oil. Faecal water was assayed for lipid peroxidation by thiobarbituric acid reactive substances (TBARs) test, and for cytolytic activity. Haemin strikingly increased the ACF size, dose-dependently, from 2.6 to 11.4 crypts/ACF (all P < 0.001). The high-haemin diet also increased the number of ACF per colon (P < 0.001). Promotion was associated with increased faecal water TBARs and cytotoxicity. Calcium, olive oil and antioxidants each inhibited the haemin-induced ACF promotion, and normalized the faecal TBARs and cytotoxicity. The haemoglobin diets increased the number of ACF and faecal TBARs, but not the ACF size or the faecal cytotoxicity. In conclusion, dietary haemin is the most potent known ACF promoter. Haemoglobin is also a potent promoter of colorectal carcinogenesis. The results suggest that myoglobin in red meat could promote colon cancer. Diets high in calcium, or in oxidation-resistant fats, may prevent the possible cancer-promoting effect of red meat.

Animals↗

PubMed2002

Naringenin from cooked tomato paste is bioavailable in men.

Naringenin has been shown to exert antiestrogenic, cholesterol-lowering and antioxidant activities, as well as an indirect modulation on the metabolism of many xenobiotics. It is one of the most abundant polyphenols in tomato. Given the widespread consumption of tomato (Lycopersicum esculentum) and tomato-based products, this study was designed to determine whether plasma levels of naringenin were detectable in five men after consumption of a test meal containing 150 mg of cooked tomato paste. Naringenin intake with the test meal was 3.8 mg. Blood was drawn from fasting subjects and 2, 4, 6, 8 and 24 h after the meal. To compare the results with a control, the same meal without tomato paste (control meal) was administered to the same subjects 2 wk later. Analyses were performed using high-performance liquid chromatography coupled with a CoulArray electrochemical detector. The peak plasma concentration was 0.12 +/- 0.03 micro mol/L 2 h after the meal. Unconjugated naringenin was not detected. Naringenin was not detected in plasma at any time after consumption of the control meal. In addition to naringenin, we detected rutin and chlorogenic acid in tomato paste, but these polyphenols and their derivatives (quercetin and caffeic acid) were not detected in plasma at any time. To the best of our knowledge, this is the first study demonstrating naringenin bioavailability in humans after consumption of a meal containing cooked tomato paste.

Adult↗

PubMed1991

Study on the mutagenic activity of 13 bioflavonoids with the Salmonella Ara test.

The mutagenicity of 13 flavonoids has been investigated with the L-arabinose forward mutation assay of Salmonella typhimurium. Each flavonoid was tested by both plate incorporation and preincubation mutagenesis protocols in the presence or the absence of mammalian metabolic activation (S9 mixture). All flavonoids gave a dose-response relationship and induced a number of AraR mutants considered statistically significant. Their minimum mutagenic doses (MMD) differed markedly in the Ara test, covering a 400-fold range: from 4 nmol for quercetin to 1626 nmol for taxifolin. Flavonols were the strongest mutagens, with mutagenic potencies (MMD-1) representing from 27 to approximately 2% that of quercetin. Comparatively, the mutagenicities of other flavonoids represented only less than or equal to 1%. The data reported in this paper for the Ara forward mutation test suggest structural requirements for mutagenicity of bioflavonoids like those previously reported for the His reverse mutation assay: (i) flavonols with a free hydroxyl at position 3 are the strongest mutagenic flavonoids, (ii) saturation of the 2,3 double bond diminishes the mutagenic potency, and (iii) free hydroxyl groups at positions 3' and 4' influence the non-requirement for metabolic activation. The mutagenic properties of quercetin and rutin in the Ara test support the idea that these flavonols are not the major putative mutagens in complex mixtures such as wine.

Arabinose↗

PubMed2004

Nitrogen supply influences herbivore-induced direct and indirect defenses and transcriptional responses in Nicotiana attenuata.

Although nitrogen (N) availability is known to alter constitutive resistance against herbivores, its influence on herbivore-induced responses, including signaling pathways, transcriptional signatures, and the subsequently elicited chemical defenses is poorly understood. We used the native tobacco, Nicotiana attenuata, which germinates in the postfire environment and copes with large changes in soil N during postfire succession, to compare a suite of Manduca sexta- and elicitor-induced responses in plants grown under high- and low-N (LN) supply rates. LN supply decreased relative growth rates and biomass by 35% at 40 d compared to high-N plants; furthermore, it also attenuated (by 39 and 60%) the elicitor-induced jasmonate and salicylate bursts, two N-intensive direct defenses (nicotine and trypsin proteinase inhibitors, albeit by different mechanisms), and carbon-containing nonvolatile defenses (rutin, chlorogenic acid, and diterpene glycosides), but did not affect the induced release of volatiles (cis-alpha-bergamotene and germacrene A), which function as indirect defenses. M. sexta and methyl jasmonate-induced transcriptional responses measured with a microarray enriched in herbivore-induced genes were also substantially reduced in plants grown under LN supply rates. In M. sexta-attacked LN plants, only 36 (45%) up-regulated and 46 (58%) down-regulated genes showed the same regulation as those in attacked high-N plants. However, transcriptional responses frequently directly countered the observed metabolic changes. Changes in a leaf's sensitivity to elicitation, an attacked leaf's waning ability to export oxylipin wound signals, and/or resource limitations in LN plants can account for the observed results, underscoring the conclusion that defense activation is a resource-intensive response.

Animals↗

PubMed1958

Assay of the capillary action of flavanoid compounds in mice.

A method is presented for the assay of biologically active flavanoids by measurement of the reduction which these compounds cause in the sensitivity of the skin capillaries of mice to histamine. The assay is economical of time, space, and apparatus. Limits of error may be calculated from internal evidence. Time/effect relationships are also given for the capillary actions of rutin and hisperidin and for some of their derivatives.

Animals↗

PubMed1998

Effect of chronic therapy with proteolytic enzymes on hypertension-induced renal injury in the rat model of Goldblatt hypertension.

This study investigated the possible beneficial effect of intraperitoneal proteolytic enzyme administration on the development of hypertension-induced renal injury in the rat model of 2-kidney 1-clip (2K1C) Goldblatt hypertension. Male Wistar rats (120-150 g) underwent either sham surgery (control, n = 5) or clipping of the left renal artery. From day one 2K1C rats were randomized into 2 groups, placebo treatment (n = 7), and proteolytic enzyme treatment (n = 9). To the verum group a fixed mixture of trypsin (2.42 mg), bromelain (4.54 mg), and rutin (5.04 mg) dissolved in 2 ml of sterile 0.9% NaCl was administered intraperitoneally daily, while the placebo group received only vehicle. Rats were pair-fed. The duration of the study was 7 weeks. All 2K1C rats developed hypertension and the mean values of systolic blood pressure (SBP) did not differ significantly between the groups at any time recorded (SBP at sacrifice: controls 122.0 +/- 8.5 mm Hg; placebo 191.4 +/- 7. 6 mm Hg; enzyme 180.5 +/- 6.5 mm Hg). Enzyme treatment prevented the rise in proteinuria (controls 12.4 +/- 2.6 mg/24 h; placebo 19.7 +/- 3.9 mg/24 h; enzyme 12.2 +/- 1.3 mg/24 h; p < 0.05) and ameliorated the increase in serum urea concentrations. Histomorphologically, signs of malignant nephrosclerosis were not found in control rats, while they were present in 4/7 (57%) of placebo-treated rats, but only in 1/9 (11%) of the enzyme-treated group. The volume fraction of renocortical interstitium was increased in both 2K1C groups in comparison with controls; however, enzyme treatment decreased the accumulation of interstitial tissue significantly (-22%) compared to placebo treatment. Cellular infiltration with mononuclear cells was also lower in the protease-treated group. To summarize, in the rat model of 2K1C hypertension, systemic treatment with proteases ameliorates the severity of nephrosclerosis and tubulointerstitial fibrosis in the non-clipped kidney, as well as proteinuria, without affecting high blood pressure.

Animals↗

PubMed1997

Interaction with type II estrogen binding sites and antiproliferative activity of tamoxifen and quercetin in human non-small-cell lung cancer.

The antiestrogen tamoxifen is thought to antagonize the effects of estrogens by competing with them for estrogen receptor (ER) binding. However, tarnoxifen can also reverse multidrug resistance, synergize with cisplatin cytotoxicity, and inhibit growth in ER-negative lung cancer cells. In addition to ERs, rat and human target tissues contain a second binding macromolecule termed the type II estrogen binding site (type II EBS). It has been shown that tamoxifen and flavonoids, a widely distributed class of natural substances with a variety of biologic actions, bind to type II EBS and inhibit the growth of several tumor cell types. At present, conflicting data about ERs and an absence of data about type II EBSs exist for lung tumors. We have tested non-small-cell lung carcinoma cell lines and primary tumor cells for the presence of ERs and type II EBSs and have evaluated the effects of tamoxifen and quercetin (pentahydroxyflavone) on the growth of these cells. Using a whole-cell assay and nuclear and cytosolic radiobinding experiments with [3H]estradiol as tracer, we have found that SK-LU1, SW900, ChaGo-K-1, H441, H661, and A549 cells, as well as primary tumors, bind estrogen specifically. This binding results mainly from the presence of a large number of type II EBSs, whereas ERs are absent or present at low concentrations. Type II EBSs bound tamoxifen and quercetin with similar affinity. Cell counts and a thymidine incorporation assay showed that both compounds inhibit cell growth in a concentration-dependent manner at concentrations ranging from 10 nM to 1 microM. Neither ipriflavone, an isoflavone, nor rutin, the 3-rhamnosylglucoside of quercetin, bound type II EBSs or inhibited cell growth. These findings suggest that tamoxifen and quercetin could regulate lung cancer cell growth through a binding interaction with type II EBSs. This mechanism could also be active in vivo, in that we have observed that nuclear and cytosolic type II EBSs were present in all primary lung cancers tested (n = 12), and that tamoxifen and quercetin were effective in inhibiting in vitro bromodeoxyuridine (BrdU) incorporation and proliferation-cell nuclear antigen expression by neoplastic cells in these cancers.

Aged↗

PubMed2000

Management of venous edema: insights from an international task force.

An International Task Force made up of a panel of 16 experts has reviewed and objectively evaluated all aspects of chronic venous disease of the leg (CVDL). All available publications on CVDL from 1983 to 1997 were identified through computerized search in Medline and by a manual search. Next, three different screenings were performed in order to select only relevant papers providing a level of scientific evidence that was considered moderate to strong. Final conclusions and further therapeutic recommendations were made based on these publications. Medication, compression, local therapy, sclerotherapy, and surgery are the accepted available therapeutic options for CVDL. For edema, the following recommendations can be made: edema is an early sign of CVDL, but before starting any treatment, nonvenous causes of edema should be excluded. Medication and compression are the therapeutic options for edema that are accepted by the Task Force. Evaluation of their efficacy is based on objective measures of edema. Several well-conducted, placebo-controlled trials have shown efficacy of drugs such as micronized purified flavonoid fraction, rutosides, calcium dobesilate, and coumarin rutin. Graduated compression stockings have been shown to be effective; compression needs to be exerted at least at 35 mm Hg. Bandages, if properly applied, both fixed and stretched, can produce favorable results. Sclerotherapy or surgery is not indicated unless there is saphenofemoral or saphenopopliteal reflux. In the absence of such reflux or following deep venous thrombosis, there is no evidence to support sclerotherapy or surgery.

Anticoagulants↗