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Highlights:
  • Researchers at the University of Washington have increased the lifespan of mice by 18.5%, by genetically engineering intracellular overexpression of the catalase enzyme.

  • Antioxidant polyphenols found in apples, particularly procyanidins and quercetin, increase catalase expression.

  • Apple polyphenol extracts also increase intracellular antioxidant activity by 400%

  • These studies have significant implications for human aging, lifespan, and the prevention and treatment of age-related disease.

 
Extension of Murine Lifespan by Overexpression of Catalase Targeted to Mitochondria, Science. 2005 May 5
Characteristics and physiological functions of polyphenols from apples, Biofactors. 2004;22(1-4):311-4.
Procyanidins protect Fao cells against hydrogen peroxide-induced oxidative stress, Biochim Biophys Acta. 2002 Aug 15;1572(1):25-30.
Influence of quercetin and rutin on growth and antioxidant defense system of a human hepatoma cell line (HepG2), Eur J Nutr. 2005 Mar 25
Reversal of haloperidol-induced orofacial dyskinesia by quercetin, a bioflavonoid,  Psychopharmacology (Berl). 2003 Jun;167(4):418-23.
The effect of quercetin on the mRNA expression of different antioxidant enzymes in hepatoma cells, Arch Toxicol. 2003 Sep;77(9):506-10.
Quercetin, a bioflavonoid, attenuates haloperidol-induced orofacial dyskinesia, Neuropharmacology. 2003 Jun;44(8):1100-6
Apple polyphenol extracts prevent damage to human gastric epithelial cells in vitro and to rat gastric mucosa in vivo, Gut 2005;54:193-200
Oxidants, antioxidants, and the degenerative diseases of aging, Proc Natl Acad Sci U S A. 1993

 

Science. 2005 May 5

Extension of Murine Lifespan by Overexpression of Catalase Targeted to Mitochondria

Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS.

Departments of Genome Sciences; Center for Molecular and Mitochondrial Medicine and Genetics, Departments of Biological Chemistry and Ecology and Evolutionary Biology, University of California, Irvine, Irvine CA 92697, USA.

To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to the peroxisome (PCAT), nucleus (NCAT), or mitochondrion (MCAT). Median and maximum lifespans were maximally increased (average 5 months, and 5.5 months, respectively) in MCAT animals. Cardiac pathology and cataract development were delayed, oxidative damage was reduced, H2O2 production and H2O2-induced aconitase inactivation were attenuated, and the development of mitochondrial deletions was reduced. These results support the free radical theory of aging and reinforce the importance of mitochondria as a source of these radicals.

PMID: 15879174 [PubMed - as supplied by publisher]

 

Biofactors. 2004;22(1-4):311-4.
Characteristics and physiological functions of polyphenols from apples.

Akazome Y.

Fundamental Research Laboratory, Asahi Breweries, Ltd., 1-21, Midori 1-chome, Moriya-shi, Ibaraki 302-0106, Japan. yoko.akazome@asahibeer.co.jp

Apples contain many kinds of polyphenols, and the main components are oligomeric procyanidins. Applephenon is apple polyphenol extract produced commercially from unripe apples, and has been used as food additive in order to prevent oxidation of components in foods and its application in functional foods is expected. In a lipid metabolism regulation study, administration of Applephenon has the potential to exert strong anti-oxidative activity and to inhibit consumption of vitamin E and anti-oxidative enzymes. Double blind clinical trials of Applephenon on pediatric patients with atopic dermatitis, and tests using type I allergic model mice suggested that Applephenon might regulate allergic reactions. We found the no observed adverse effect level (NOAEL) of Applephenon is greater than 2000 mg/kg in a 90~day consecutive oral administration toxicity test in rats, and Applephenon is safe and acceptable based on mutagenicity tests.

PMID: 15630302 [PubMed - in process]
Biochim Biophys Acta. 2002 Aug 15;1572(1):25-30.
 
Procyanidins protect Fao cells against hydrogen peroxide-induced oxidative stress

Roig R, Cascon E, Arola L, Blade C, Salvado MJ.

Departament de Bioquimica i Biotecnologia, Unitat d'Enologia del Centre de Referencia en Tecnologia dels Aliments de la Generalitat de Catalunya, Universitat Rovira i Virgili, Imperial Tarraco, 1, E-43005 Tarragona, Spain.

In this paper, we evaluate the extent to which flavonoids in red wine (catechin, epicatechin, quercetin and procyanidins) protect against hydrogen peroxide-induced oxidative stress in Fao cells. When cells were exposed to H(2)O(2), malondialdehyde (MDA) levels, oxidized glutathione (GSSG) levels and lactate dehydrogenase (LDH) release increased, indicating membrane damage and oxidative stress. All the flavonoids studied, and in particular epicatechin and quercetin, protected the plasma membrane. Only procyanidins lowered MDA levels and LDH leakage, maintained a higher reduced/oxidized glutathione ratio, and increased catalase/superoxide dismutase and glutathione peroxidase/superoxide dismutase ratios, and glutathione reductase and glutathione transferase activities. These results show that the procyanidin mixture has a greater antioxidant effect than the individual flavonoids studied, probably due to its oligomer content and/or the additive/synergistic effect of its compounds. This suggests that the mixture of flavonoids found in wine has a greater effect than individual phenols, which may explain many of the healthy effects attributed to wine.

PMID: 12204329 [PubMed - indexed for MEDLINE]

 

Eur J Nutr. 2005 Mar 25
 
Influence of quercetin and rutin on growth and antioxidant defense system of a human hepatoma cell line (HepG2).

Alia M, Mateos R, Ramos S, Lecumberri E, Bravo L, Goya L.

Depto. de Metabolismo y Nutricion, Instituto del Frio (CSIC) C/Jose Antonio Novais, 10. Ciudad Universitaria, 28040, Madrid, Espana, luisgoya@if.csic.es.

BACKGROUND : Dietary polyphenols like quercetin and rutin are considered beneficial because of their potential protective role in the pathogenesis of multiple diseases associated to oxidative stress such as cancer, coronary heart disease and atherosclerosis. However, many of these effects may depend on the concentration of the polyphenol utilized since high doses of some phenolic compounds may be prooxidant and negatively affect cell growth and viability. AIM OF THE STUDY : To test the potential chemoprotective effects of quercetin and rutin, two flavonols with high antioxidant capacity, on cell growth, viability and the response of the antioxidant defense system of a human hepatoma cell line (HepG2). METHODS : Cell growth was measured by diaminobenzoic acid and bromodeoxyuridine assays, cell toxicity by lactate dehydrogenase leakage assay, reduced glutathione was quantified by a fluorimetric assay, cellular malondialdehyde was analyzed by high-performance liquid chromatography, reactive oxygen species were quantified by the dichlorofluorescein assay, antioxidant enzyme activities were determined by spectrophotometric analysis and their gene expression by northern blot. RESULTS : Shortterm exposure (4 h) to these flavonols had no antiproliferative nor cytotoxic effect. High doses of quercetin (50-100 microM) increased glutathione concentration and gene expression of Cu/Zn superoxide dismutase and catalase inhibiting the activity of the latter enzyme, whereas lower doses (0.1-1 microM) decreased gene expression of Cu/Zn superoxide dismutase and increased that of glutathione peroxidase. All doses of quercetin and rutin diminished reactive oxygen species and high doses (10-100 microM) decreased malondialdehyde concentration. CONCLUSION : The results indicate that both natural antioxidants induce favorable changes in the antioxidant defense system of cultured HepG2 that prevent or delay conditions which favor cellular oxidative stress.

PMID: 15782287 [PubMed - as supplied by publisher]

 

Psychopharmacology (Berl). 2003 Jun;167(4):418-23.

Reversal of haloperidol-induced orofacial dyskinesia by quercetin, a bioflavonoid.

Naidu PS, Singh A, Kulkarni SK.

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, 160014 Chandigarh, India.

RATIONALE: Tardive dyskinesia is a serious neurological syndrome associate with long-term administration of neuroleptics to humans and experimental animals. It may be caused by loss of dopaminergic cells, due to free radicals as a product of high synaptic dopamine levels. Quercetin is a bioflavonoid with strong antioxidant properties. OBJECTIVES: To evaluate the effect of chronic quercetin treatment on haloperidol-induced orofacial dyskinesia. METHODS: Vacuous chewing movements (VCM) in rats, a widely accepted animal model of tardive dyskinesia was employed in the present study. VCM were induced in rats by daily administration of haloperidol (1.0 mg/kg) for a period of 21 days. Animals with established dyskinesia were given quercetin for a period of 4 weeks and behavioral scoring was recorded every week before administration of quercetin. Animals were killed after the last behavioral recordings and biochemical estimations were carried out. RESULTS: Chronic haloperidol (1.0 mg/kg for 21 days) treatment significantly induced VCM and tongue protrusions in rats and quercetin (25-100 mg/kg for 4 weeks) significantly reversed haloperidol-induced VCM and tongue protrusions. Biochemical analysis revealed that chronic haloperidol treatment significantly induced lipid peroxidation, decreased glutathione (GSH), superoxide dismutase (SOD), and catalase levels in the brains of rats. Quercetin (25-100 mg/kg for 4 weeks) significantly reduced lipid peroxidation and restored GSH, SOD and catalase levels. CONCLUSIONS: The results of the present study clearly indicate that quercetin has a protective role against haloperidol-induced orofacial dyskinesia. Consequently, the use of quercetin as a therapeutic agent for the treatment of tardive dyskinesia should be considered.

PMID: 12669184 [PubMed - indexed for MEDLINE]

 

Arch Toxicol. 2003 Sep;77(9):506-10. Epub 2003 May 20.
 
The effect of quercetin on the mRNA expression of different antioxidant enzymes in hepatoma cells.

Rohrdanz E, Bittner A, Tran-Thi QH, Kahl R.

Bundesinstitut fur Arzneimittel und Medizinprodukte, Kurt-Georg-Kiesinger Allee 3, 53175 Bonn, Germany. e.roehrdanz@bfarm.de

The flavonol quercetin shows a wide range of effects in biological systems. We investigated whether quercetin exerts its proposed antioxidant properties via the antioxidant enzyme system. Quercetin in a concentration range from 5 to 100 microM decreased manganese superoxide dismutase, glutathione peroxidase, and copper zinc superoxide dismutase mRNA expression levels each by 30-40% in rat hepatoma H4IIE cells.
Catalase mRNA expression levels increased about 30% but only with the cytotoxic concentration of 100 microM. Despite the down-regulation of antioxidant enzyme mRNA expression quercetin treatment of cells induced only a mild oxidative stress. Pretreatment of H4IIE cells with quercetin even protected against an oxidative stress resulting from hydrogen peroxide exposure. In conclusion, the antioxidant capacity of quercetin was shown not to be due to the antioxidant enzyme system.

PMID: 12756520 [PubMed - indexed for MEDLINE]

 

Neuropharmacology. 2003 Jun;44(8):1100-6.
 
Quercetin, a bioflavonoid, attenuates haloperidol-induced orofacial dyskinesia.

Naidu PS, Singh A, Kulkarni SK.

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, -160014, Chandigarh, India.

Chronic treatment with neuroleptics leads to the development of abnormal orofacial movements described as vacuous chewing movements (VCMs) in rats. Vacuous chewing movements in rodents are widely accepted as one of the animal models of tardive dyskinesia. Oxidative stress and the products of lipid peroxidation are implicated in the pathophysiology of various neurological disorders including tardive dyskinesia. In the present study chronic haloperidol (1.0 mg kg(-1) for 21 days) treatment induced vacuous chewing movements and tongue protrusions in rats. Co-administration of quercetin, a bioflavonoid, dose dependently (25-100 mg kg(-1)) reduced haloperidol-induced vacuous chewing movements and tongue protrusions. Biochemical analysis revealed that chronic haloperidol treatment induces lipid peroxidation and decreases the glutathione (GSH) levels in the forebrains of rats. The antioxidant defense enzymes, superoxide dismutase (SOD) and catalase were also decreased due to chronic haloperidol treatment. Co-administration of quercetin (25-100 mg kg(-1)) significantly reduced the lipid peroxidation and restored the decreased glutathione levels in these animals. Further quercetin (50-100 mg kg(-1)) also reversed the haloperidol-induced decrease in forebrain SOD and catalase levels in rats. The major findings of the present study suggested that oxidative stress plays a significant role in neuroleptic-induced orofacial dyskinesia and quercetin co-administration reverses these behavioral and biochemical changes. Quercetin, a naturally occurring bioflavonoid could prove to be a useful agent in neuroleptic-induced orofacial dyskinesia.

PMID: 12763102 [PubMed - indexed for MEDLINE]

 

Gut 2005;54:193-200
Apple polyphenol extracts prevent damage to human gastric epithelial cells in vitro and to rat gastric mucosa in vivo

G Graziani1, G D’Argenio2, C Tuccillo3, C Loguercio3, A Ritieni1, F Morisco1, C Del Vecchio Blanco3, V Fogliano1 and M Romano3

1 Dipartimento di Scienza degli Alimenti, Università di Napoli "Federico II" Parco Gussone, Ed 84-80055 Portici (NA), Italy
2 Gastroenterologia, Università Federico II, Napoli, Italy
3 Centro Interuniversitario di Ricerche su Alimenti, Nutrizione ed Apparato Digerente (CIRANAD) and Dipartimento Medico Chirurgico di Internistica Clinica e Sperimentale, Cattedra di Gastroenterologia y Seconda Università di Napoli, Napoli, Italy

Correspondence to:
Dr M Romano
Dipartimento di Internistica Clinica e Sperimentale-Gastroenterologia, II Policlinico, Edificio 3, II piano, Via Pansini 5, 80131 Napoli, Italy; marco.romano@unina2.it

Background: Fresh fruit and vegetables exert multiple biological effects on the gastrointestinal mucosa.

Aim: To assess whether apple extracts counteract oxidative or indomethacin induced damage to gastric epithelial cells in vitro and to rat gastric mucosa in vivo.

Methods: Apple extracts were obtained from freeze dried apple flesh of the "Annurca" variety. Cell damage was induced by incubating MKN 28 cells with xanthine-xanthine oxidase or indomethacin and quantitated by MTT. In vivo gastric damage was induced by indomethacin 35 mg/kg. Intracellular antioxidant activity was determined using the (2,2'-azinobis (3-ethylbenzothiazolin-6-sulfonate) method. Malondialdehyde intracellular concentration, an index of lipid peroxidation, was determined by high pressure liquid chromatography with fluorometric detection.

Results: (1) Apple extracts decreased xanthine-xanthine oxidase or indomethacin induced injury to gastric epithelial cells by 50%; (2) catechin or chlorogenic acid (the main phenolic components of apple extracts) were equally effective as apple extracts in preventing oxidative injury to gastric cells; and (3) apple extracts (i) caused a fourfold increase in intracellular antioxidant activity, (ii) prevented its decrease induced by xanthine-xanthine oxidase, (iii) counteracted xanthine-xanthine oxidase induced lipid peroxidation, and (iv) decreased indomethacin injury to the rat gastric mucosa by 40%.

Conclusions: Apple extracts prevent exogenous damage to human gastric epithelial cells in vitro and to the rat gastric mucosa in vivo. This effect seems to be associated with the antioxidant activity of apple phenolic compounds. A diet rich in apple antioxidants might exert a beneficial effect in the prevention of gastric diseases related to generation of reactive oxygen species.

 

Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915-22
Oxidants, antioxidants, and the degenerative diseases of aging.

 
Ames BN, Shigenaga MK, Hagen TM.

Division of Biochemistry and Molecular Biology, University of California, Berkeley 94720.

Metabolism, like other aspects of life, involves tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids. Dietary fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day, the opportunity for improving health by improving diet is great.

Publication Types:
  • Review


PMID: 8367443 [PubMed - indexed for MEDLINE]

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