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Clinical Studies
References
This bioflavonoid occurs in many plant foods. Quercetin has a synergistic effect with ephedrine and caffeine, increasing and prolonging their properties. Quercetin acts as a potent antioxidant and inhibits inflammatory and allergic reactions by inhibiting histamine release and other allergy-mediating compounds.
Quercetin may also reduce capillary fragility, and it may offer protection against diabetic cataracts by inhibiting aldose reductase in the lens. Quercetin might reduce cancer risk by inactivating malignant precursors or by inhibiting carcinogenesis. Preliminary studies suggest it might have inhibitory effects on various cancer types, including breast, leukemia, colon, ovary, oral squamous cell, endometrial, gastric and non-small-cell lung carcinomas. Quercetin has antiestrogenic effects in cultures of breast cancer cells.
Quercetin may be beneficial in benign prostatic hyperplasia (BPH), alopecia, hirsutism, androgen-dependent disorders, bacterial prostatitis, prostate cancer, atherosclerosis, hypercholesterolemia, coronary heart disease, vascular insufficiency, diabetes, cataracts, allergies, allergic rhinitis, peptic ulcer, schizophrenia, inflammation, asthma, gout, viral infections such as herpes simplex virus and in preventing cancer.
Published Clinical Studiesclin
1
Inhibition of prostate cancer cell colony formation by the flavonoid quercetin correlates with modulation of specific regulatory genes.
Nair HK, Rao KV, Aalinkeel R, Mahajan S, Chawda R, Schwartz SA.
Division of Allergy, Immunology and Rheumatology, Department of Medicine. Department of Microbiology and Immunology. State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14203.
The natural product quercetin is a flavonoid found in many fruits and vegetables. Previous research has shown that quercetin has antitumor, anti-inflammatory, antiallergic, and antiviral activities. In the present investigation we studied the effect of quercetin on the ability of prostate cancer cell lines with various degrees of aggressive potential to form colonies in vitro. Specifically, we examined the molecular mechanisms underlying this effect, including the expression of cell cycle and tumor suppressor genes as well as oncogenes. We observed that quercetin at concentrations of 25 and 50 micro M significantly inhibited the growth of the highly aggressive PC-3 prostate cancer cell line and the moderately aggressive DU-145 prostate cancer cell line, whereas it did not affect colony formation by the poorly aggressive LNCaP prostate cancer cell line or the normal fibroblast cell line BG-9. Using the gene array methodology, we found that quercetin significantly inhibited the expression of specific oncogenes and genes controlling G(1), S, G(2), and M phases of the cell cycle. Moreover, quercetin reciprocally up-regulated the expression of several tumor suppressor genes. In conclusion, our results demonstrate that the antitumor effects of quercetin directly correlate with the aggressive potential of prostate cancer cells and that the mechanism(s) of quercetin-mediated antitumor effects may involve up-regulation of tumor suppressor genes and reciprocal down-regulation of oncogenes and cell cycle genes. The results of these studies provide a scientific basis for the potential use of flavonoids as nutraceuticals in the chemoprevention of cancer.
PMID: 14715546 [PubMed - in process]
2
Nutritional and botanical modulation of the inflammatory cascade--eicosanoids, cyclooxygenases, and lipoxygenases--as an adjunct in cancer therapy.
Wallace JM.
Nutritional Solutions, Inc., 2935 North, 1000 East, North Logan, UT 84341, USA. BTnutrition@aol.com
Emerging on the horizon in cancer therapy is an expansion of the scope of treatment beyond cytotoxic approaches to include molecular management of cancer physiopathology. The goal in these integrative approaches, which extends beyond eradicating the affected cells, is to control the cancer phenotype. One key new approach appears to be modulation of the inflammatory cascade, as research is expanding that links cancer initiation, promotion, progression, angiogenesis, and metastasis to inflammatory events. This article presents a literature review of the emerging relationship between neoplasia and inflammatory eicosanoids (PGE2 and related prostaglandins), with a focus on how inhibition of their synthesizing oxidases, particularly cyclooxygenase (COX), offers anticancer actions in vitro and in vivo. Although a majority of this research emphasizes the pharmaceutical applications of nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors, these agents fail to address alternate pathways available for the synthesis of proinflammatory eicosanoids. Evidence is presented that suggests the inhibition of lipoxygenase and its by-products-LTB4, 5-HETE, and 12-HETE-represents an overlooked but crucial component in complementary cancer therapies. Based on the hypothesis that natural agents capable of modulating both lipoxygenase and COX may advance the efficacy of cancer therapy, an overview and discussion is presented of dietary modifications and selected nutritional and botanical agents (notably, omega-3 fatty acids, antioxidants, boswellia, bromelain, curcumin, and quercetin) that favorably influence eicosanoid production.
PMID: 14664746 [PubMed - in process]
3
Reversal of aging and chronic ethanol-induced cognitive dysfunction by quercetin a bioflavonoid.
Singh A, Naidu PS, Kulkarni SK.
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
Cognitive dysfunction, one of the most striking age-related impairments seen in human beings, has been correlated to the vulnerability of the brain to increased oxidative stress during aging process. Quercetin is a bioflavonoid with strong antioxidant properties. Experiments were performed to study the possible effects of quercetin on cognitive performance of young, aged or ethanol-intoxicated mice (an animal model for cognition dysfunction) using one trail step down type of passive avoidance and elevated plus maze tasks, respectively. Aged or chronic ethanol-treated mice showed poor retention of memory in step-down passive avoidance and in elevated plus-maze task. Chronic administration of quercetin (10, 25 and 50 mg/kg) for 30 days or its co-administration with ethanol (15% w/v, 2g/kg per orally) for 24 days significantly reversed the age-related or chronic ethanol-induced retention deficits in both the test paradigms. However, in both memory paradigms chronic administration of quercetin failed to modulate the retention performance of young mice. Chronic quercetin administration for 30 days also reversed age associated increase in TBARS levels and decline in forebrain total glutathione (GSH), SOD and catalase levels. Chronic ethanol administration to young mice produced an increase in lipid peroxidation, and a decline in forebrain total glutathione (GSH), SOD and catalase levels, which was significantly reversed by the co-administration of quercetin (10, 25 and 50 mg/kg). The results of the present study showed that chronic quercetin treatment reverses cognitive deficits in aged and ethanol-intoxicated mice, which is associated with its antioxidant property.
PMID: 14703737 [PubMed - in process]
4
Effects of flavonoids on glutathione and glutathione-related enzymes in cisplatin-treated L1210 leukemia cells.
Cipak L, Berczeliova E, Paulikova H.
Cancer Research Institute; Slovak Academy of Sciences, Bratislava, 833 91 Slovak Republic. exoncip@savba.sk
Connections between the ability of quercetin (Qu)and galangin (Ga) to differentially modulate cis-Pt-induced apoptosis and their effects on glutathione system of murine L1210 leukemia cells were studied. The results showed that total glutathione (GSHt) level is increased significantly (cca 123% of control level), both in cells treated with 10 microM Qu and in cells treated with 4 microM cis-Pt and 10 microM Qu in combination. 10 microM Ga had no effect on GSHt content. Activities of glutathione S-transferase (GST) and glutathione reductase (GR) were not changed significantly when 10 microM flavonoids were used. Significant inhibition of GR activity was observed when flavonoids were used in concentrations higher than 25 microM.The presented data indicate that Qu change the redox state of the cells that is implicated in regulation of apoptosis, due to its ability to increase the GSHt level, and thus may potentiate cis-Pt-induced apoptosis of L1210 cells.
PMID: 14689067 [PubMed - in process]
Reversal of reserpine-induced orofacial dyskinesia and cognitive dysfunction by quercetin.5
Naidu PS, Singh A, Kulkarni SK.
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Tardive dyskinesia (TD) is a serious neurological syndrome associated with long-term administration of neuroleptics to humans and experimental animals. The pathophysiology of this disabling and commonly irreversible movement disorder is still obscure. It may be caused by a loss of dopaminergic cells or may be due to free radicals as a product of high synaptic dopamine levels. Quercetin is a bioflavonoid with strong antioxidant properties. Repeated treatment with reserpine (1.0 mg/kg) on each other day for a period of 5 days (days 1, 3 and 5) significantly induced vacuous chewing movements (VCMs) and tongue protrusions (TPs) in rats. Chronic treatment with quercetin for a period of 4 weeks to reserpine-treated animals significantly and dose dependently (50 and 100 mg/kg) reduced the reserpine-induced VCMs and TPs. Reserpine-treated animals also showed poor retention of memory in elevated plus-maze task paradigm. Chronic quercetin administration significantly reversed reserpine-induced retention deficits. Biochemical analysis revealed that chronic reserpine treatment significantly induced lipid peroxidation and decreased the glutathione (GSH) levels in the brains of rats. Chronic reserpine-treated rats showed decreased levels of antioxidant defense enzymes, superoxide dismutase (SOD) and catalase. Chronic administration of quercetin dose dependently (50-100 mg/kg) and significantly reduced the lipid peroxidation and restored the decreased GSH levels by chronic reserpine treatment. It also significantly reversed the reserpine-induced decrease in brain SOD and catalase levels in rats. The results of the present study clearly indicated that quercetin has a protective role against reserpine-induced orofacial dyskinesia and memory impairment. Consequently, the use of quercetin as a therapeutic agent for the treatment of TD should be considered. Copyright 2004 S. Karger AG, Basel
PMID: 14685008 [PubMed - in process]
6
Comparative vasodilating actions among terpenoids and flavonoids contained in Ginkgo biloba extract.
Nishida S, Satoh H.
Department of Pharmacology, Division of Crude and Herbal Medicine, Nara Medical University, Kashihara, 634-8521, Nara, Japan
BACKGROUND: Comparative vasodilating actions of the constituents of Ginkgo biloba extract (GBE), terpenoids (bilobalide, ginkgolides A, B and C) and flavonoids (quercetin and rutin), were examined using rat aorta ring strips. METHODS: Cumulative administrations of GBE and its constituents were followed with the pretreatment of 5 micromol/l NE. RESULTS: GBE at 0.03 to 3 mg/ml had a potent concentration-dependent relaxation; by 70+/-4.5% (n=6, P<0.001) at 3 mg/ml. Terpenoids and flavonoids at 0.1 to 100 micromol/l had potent concentration-dependent relaxation. At 100 micromol/l, bilobalide dilated by 17.6+/-3.9% (n=7, P<0.05), and ginkgolides A, B and C also caused it to the almost same extent. Quercetin (100 micromol/l) caused a potent vasorelaxation by 49.9+/-4.8% (n=10, P<0.001). Rutin at 100 micromol/l had weaker vasorelaxation; by 13.7+/-3.2% (n=6, P<0.01). CONCLUSIONS: All constituents of GBE have the concentration-dependent vasorelaxtant effect. The potency of GBE's action was not made simply by addition of those of the constituents. Each constituent itself would contribute to the GBE-induced vasodilation, although the constituents have the complicated interactions with each other.
PMID: 14687903 [PubMed - in process]
Cell culture protection and in vivo neuroprotective capacity of flavonoids.7
Dajas F, Rivera F, Blasina F, Arredondo F, Echeverry C, Lafon L, Morquio A, Heizen H.
Department of Neurochemistry, Instituto de Investigaciones Biologicas Clemente Estable, Avda Italia 3318, 11600 Montevideo, Uruguay. fdajas@iibce.edu.uy
Flavonoids are an important group of recognized antioxidants ubiquitous in fruits, vegetables and herbs. There are epidemiological evidences for the stroke-protecting capacity of flavonoids and while the neuroprotective power of complex extracts rich in flavonoids like those of Ginkgo biloba, green tea or lyophilized red wine have been demonstrated in several studies, neuroprotection by individual flavonoids has been poorly studied in vivo. The neuroprotective capacity of individual flavonoids was studied in PC12 cells in culture and in a model of permanent focal ischemia (permanent Middle Cerebral Artery Occlusion - pMCAO). In the in vivo experiments, flavonoids were administered in lecithin preparations to facilitate the crossing of the blood brain barrier. The simultaneous incubation of PC12 cells with 200 micro M hydrogen peroxide (H2O2) and different flavonoids for 30 min resulted in a conspicuous profile: quercetin, fisetin, luteolin and myricetin significantly increased cell survival while catechin, kaempherol and taxifolin did not. Quercetin was detected in brain tissue 30 min and 1 h after intraperitoneal administration. When one of the protective flavonoids (quercetin) and one of those that failed to increase PC12 cell survival (catechin) were assessed for their protective capacity in the pMCAO model, administered i.p. 30 min after vessel occlusion, quercetin significantly decreased the brain ischemic lesion while catechin did not. It is concluded that when administered in liposomal preparations, flavonoids structurally related to quercetin could become leads for the development of a new generation of molecules to be clinically effective in human brain ischemia.
PMID: 14715446 [PubMed - in process]
Neuroprotection by flavonoids.8
Dajas F, Rivera-Megret F, Blasina F, Arredondo F, Abin-Carriquiry JA, Costa G, Echeverry C, Lafon L, Heizen H, Ferreira M, Morquio A.
Departamento de Neuroquimica, Instituto de Investigaciones Biol gicas Clemente Estable, Universidade da Republica.
The high morbidity, high socioeconomic costs and lack of specific treatments are key factors that define the relevance of brain pathology for human health and the importance of research on neuronal protective agents. Epidemiological studies have shown beneficial effects of flavonoids on arteriosclerosis-related pathology in general and neurodegeneration in particular. Flavonoids can protect the brain by their ability to modulate intracellular signals promoting cellular survival. Quercetin and structurally related flavonoids (myricetin, fisetin, luteolin) showed a marked cytoprotective capacity in in vitro experimental conditions in models of predominantly apoptotic death such as that induced by medium concentrations (200 M) of H2O2 added to PC12 cells in culture. Nevertheless, quercetin did not protect substantia nigra neurons in vivo from an oxidative insult (6-hydroxydopamine), probably due to difficulties in crossing the blood-brain barrier. On the other hand, treatment of permanent focal ischemia with a lecithin/quercetin preparation decreased lesion volume, showing that preparations that help to cross the blood-brain barrier may be critical for the expression of the effects of flavonoids on the brain. The hypothesis is advanced that a group of quercetin-related flavonoids could become lead molecules for the development of neuroprotective compounds with multitarget anti-ischemic effects.
PMID: 14666245 [PubMed - in process]
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