BACKGROUND: QR-333, a topical compound that contains quercetin, a flavonoid with aldose reductase inhibitor effects, ascorbyl palmitate, and vitamin D(3), was formulated to decrease the oxidative stress that contributes to peripheral diabetic neuropathy and thus alleviate its symptoms. This proof-of-principle study assessed the efficacy and safety of QR-333 against placebo in a small cohort of patients with diabetic neuropathy. METHODS: This randomized, placebo-controlled, double-blind trial included 34 men and women (21-71 years of age) with Type 1 or 2 diabetes and diabetic neuropathy who applied QR-333 or placebo (2:1 ratio), three times daily for 4 weeks, to each foot where symptoms were experienced. Five-point scales were used to determine changes from baseline to endpoint in symptoms and quality of life (efficacy). Safety was assessed through concomitant medications, adverse events, laboratory evaluations, and physical examinations. RESULTS: QR-333 reduced the severity of numbness, jolting pain, and irritation from baseline values. Improvements were also seen in overall and specific quality-of-life measures. QR-333 was well tolerated. Eleven patients in the QR-333 group reported 23 adverse events (all mild or moderate); 4 in the placebo group reported 5 events (all moderate). One patient who applied QR-333 noted a pricking sensation twice, the only adverse event considered possibly related to study treatment. CONCLUSIONS: From this preliminary safety study, it appears that QR-333 may safely offer relief of symptoms of diabetic neuropathy and improve quality of life. These findings warrant further investigation of this topical compound.

By early February 2006, the World Health Organization had reported 165 human cases of H5N1 influenza since December 2003, with 88 fatalities. However, the avian H5N1 influenza virus apparently is not yet efficiently transmitted between humans. Though a near-term possibility of a global H5N1 influenza pandemic remains, currently there is no vaccine or anti-viral drug that is proven to be safe and effective in preventing or treating H5N1 influenza in humans. There is thus a compelling public interest in developing alternative prophylaxis and treatment strategies for H5N1 influenza, which would need to address the complex pathogenesis of H5N1 influenza that is responsible for its apparently unusually high virulence. The authors present here a significant body of medical and scientific evidence to support the prophylactic use of a carefully designed nutritional supplement formulation that may antagonize the major pathogenic processes of H5N1 influenza in humans. Through several independently-mediated mechanisms, the formulations may: (a) degrade H5N1 virulence by directly affecting the virus itself, (b) inhibit H5N1 viral replication by maintaining cellular redox equilibrium in host cells, (c) inhibit H5N1 replication by a blockade of the nuclear-cytoplasmic translocation of the viral ribonucleoproteins and reduced expression of late viral proteins related to the inhibition of protein kinase C activity and its dependent pathways, (d) down-regulate activation and proliferation of proinflammatory cytokines in respiratory epithelial cells and macrophages that are implicated in the pathogenesis of H5N1 influenza, and (e) protect the lungs and other vital organs from virus- and cytokine-induced oxidative stress by supplying and maintaining sufficient levels of exogenous and endogenous antioxidants. Key mediators in these processes include selenium, vitamin E, NAC/glutathione, resveratrol, and quercetin. Taken prophylactically, and throughout the duration and recovery of an H5N1 infection, the nutritional supplement formula may aid humans infected with H5N1 influenza to survive with a reduced likelihood of major complications, and may provide a relatively low-cost strategy for individuals as well as government, public-health, medical, health-insurance, and corporate organizations to prepare more prudently for an H5N1 pandemic. Some evidence also indicates that the supplement formulation may be effective as an adjunctive to H5N1 vaccine and anti-viral treatments, and should be tested as such.

The mango leaf extract rich in mangiferin Zynamiteimproves exercise performance when combined with luteolin or quercetin ingested at least 48 h prior to exercise. To determine whether a single dose of Zynamiteadministered 1 h before exercise increases repeated-sprint performance, 20 men and 20 women who were physically active were randomly assigned to three treatments following a double-blind cross-over counterbalanced design. Treatment A, 140 mg of Zynamite, 140 mg of quercetin, 147.7 mg of maltodextrin, and 420 mg of sunflower lecithin; Treatment B, 140 mg of Zynamite, 140 mg of quercetin, and 2126 mg of maltodextrin and Treatment C, 2548 mg of maltodextrin (placebo). Subjects performed three Wingate tests interspaced by 4 min and a final 15 s sprint after ischemia. Treatments A and B improved peak power output during the first three Wingates by 2.8% and 3.8%, respectively (treatment x sprint interaction,= 0.01). Vastus Lateralis oxygenation (NIRS) was reduced, indicating higher Oextraction (treatment× sprint interaction,= 0.01). Improved Oextraction was observed in the sprints after ischemia (= 0.008; placebo vs. mean of treatments A and B). Blood lactate concentration was 5.9% lower after the ingestion of Zynamite® with quercetin in men (treatment by sex interaction,= 0.049). There was a higher Vastus Lateralis Oextraction during 60 s ischemia with polyphenols (treatment effect,= 0.03), due to the greater muscle VOin men (= 0.001). In conclusion, a single dose of Zynamitecombined with quercetin one hour before exercise improves repeated-sprint performance and muscle Oextraction and mitochondrial Oconsumption during ischemia. No advantage was obtained from the addition of phospholipids.

Ovarian cancer is the deadliest gynecological malignancy in women, and fifth leading cause of death. Despite advances made in chemotherapy and surgery, the average time of clinical remission is approximately 2 years and the 5-year survival rate is 45%. Thus, there is an urgent need for the development of a novel therapeutic approach to ovarian cancer treatment. We investigated the effect of a specific nutrient mixture (EPQ) containing ascorbic acid, lysine, proline, green tea extract, and quercetin on human ovarian cancer cell A-2780 in vivo and in vitro. Athymic female nude mice (n = 12) were all inoculated intraperitoneally (IP) with 2× 10⁶ cells in 0.1 mL of phosphate buffered saline (PBS) and randomly divided into two groups. Upon injection, the Control group (n = 6) was fed a regular diet and the EPQ group (n = 6) a regular diet supplemented with 0.5% EPQ. Four weeks later, the mice were sacrificed and tumors that developedin the ovary were excised, weighed, and processed for histology. Lungs were inspected for metastasis. In vitro, A-2780 cells were cultured in Dulbecco modified Eagle medium supplemented with 10% FBS and antibiotics. At near confluence, cells were treated with EPQ in triplicate at concentrations between 0 and 1000 μg/mL. Cell proliferation was measured via MTT assay, MMP-9 secretion via gelatinase zymography, invasion through Matrigel and morphology via hematoxylin and eosin (H& E) staining. All Control mice developed large ovarian tumors, whereas 5 out of 6 mice in the EPQ group developed no tumors, and one, a small tumor. Control mice also showed lung metastasis in 6 out of 6 mice, while no lung metastasis was evident in EPQ mice. Zymography demonstrated only MMP-9 expression, which EPQ inhibited in a dose-dependent fashion, with virtual total block at 250μg/mL concentration. EPQ significantly inhibited invasion through Matrigel with total block at 250 μg/mL concentration. MTT showed dose-dependent inhibition of cell proliferation with EPQ, and H& E staining showed no morphological changes below 500μg/mL EPQ. These results suggest that EPQ has therapeutic potential in the treatment of ovarian cancer by significantly suppressing ovarian tumor incidence and growth and lung metastasis, and by inhibiting MMP-9 secretion and invasion of A-2780 ovarian cancer cells.

Porcine epidemic diarrhea virus (PEDV) is the predominant cause of severe entero-pathogenic diarrhea in swine. The lack of effective therapeutical treatment underlines the importance of research for new antivirals. In this study, we identified Q7R, which actively inhibited PEDV replication with a 50% inhibitory concentration (IC(50)) of 0.014 microg/mL. The 50% cytotoxicity concentration (CC(50)) of Q7R was over 100 microg/mL and the derived therapeutic index was 7142. Several structural analogues of Q7R, quercetin, apigenin, luteolin and catechin, also showed moderate anti-PEDV activity. Antiviral drugs and natural compounds revealed ribavirin, interferon-alpha, coumarin and tannic acid have relative weaker efficacy compared to Q7R. Q7R did not directly interact with or inactivate PEDV particles and affect the initial stage of PEDV infection by interfering of PEDV replication. Also, the effectiveness of Q7R against the other two viruses (TGEV, PRCV) was lower compared to PEDV. Q7R could be considered as a lead compound for development of anti-PEDV drugs to may be used to during the early stage of PEDV replication and the structure-activity data of Q7R may usefully guideline to design other related antiviral agents.

Porcine epidemic diarrhea virus (PEDV) is the predominant cause of severe entero-pathogenic diarrhea in swine. The lack of effective therapeutical treatment underlines the importance of research for new antivirals. In this study, we identified Q7R, which actively inhibited PEDV replication with a 50% inhibitory concentration (IC(50)) of 0.014 microg/mL. The 50% cytotoxicity concentration (CC(50)) of Q7R was over 100 microg/mL and the derived therapeutic index was 7142. Several structural analogues of Q7R, quercetin, apigenin, luteolin and catechin, also showed moderate anti-PEDV activity. Antiviral drugs and natural compounds revealed ribavirin, interferon-alpha, coumarin and tannic acid have relative weaker efficacy compared to Q7R. Q7R did not directly interact with or inactivate PEDV particles and affect the initial stage of PEDV infection by interfering of PEDV replication. Also, the effectiveness of Q7R against the other two viruses (TGEV, PRCV) was lower compared to PEDV. Q7R could be considered as a lead compound for development of anti-PEDV drugs to may be used to during the early stage of PEDV replication and the structure-activity data of Q7R may usefully guideline to design other related antiviral agents.

As part of our search for botanical sources of SARS-CoV 3CL(pro) inhibitors, we selected Torreya nucifera, which is traditionally used as a medicinal plant in Asia. The ethanol extract of T. nucifera leaves exhibited good SARS-CoV 3CL(pro) inhibitory activity (62% at 100μg/mL). Following bioactivity-guided fractionation, eight diterpenoids (1-8) and four biflavonoids (9-12) were isolated and evaluated for SARS-CoV 3CL(pro) inhibition using fluorescence resonance energy transfer analysis. Of these compounds, the biflavone amentoflavone (9) (IC(50)=8.3μM) showed most potent 3CL(pro) inhibitory effect. Three additional authentic flavones (apigenin, luteolin and quercetin) were tested to establish the basic structure-activity relationship of biflavones. Apigenin, luteolin, and quercetin inhibited 3CL(pro) activity with IC(50) values of 280.8, 20.2, and 23.8μM,respectively. Values of binding energy obtained in a molecular docking study supported the results of enzymatic assays. More potent activity appeared to be associated with the presence of an apigenin moiety at position C-3' of flavones, as biflavone had an effect on 3CL(pro) inhibitory activity.

As part of our search for botanical sources of SARS-CoV 3CL(pro) inhibitors, we selected Torreya nucifera, which is traditionally used as a medicinal plant in Asia. The ethanol extract of T. nucifera leaves exhibited good SARS-CoV 3CL(pro) inhibitory activity (62% at 100μg/mL). Following bioactivity-guided fractionation, eight diterpenoids (1-8) and four biflavonoids (9-12) were isolated and evaluated for SARS-CoV 3CL(pro) inhibition using fluorescence resonance energy transfer analysis. Of these compounds, the biflavone amentoflavone (9) (IC(50)=8.3μM) showed most potent 3CL(pro) inhibitory effect. Three additional authentic flavones (apigenin, luteolin and quercetin) were tested to establish the basic structure-activity relationship of biflavones. Apigenin, luteolin, and quercetin inhibited 3CL(pro) activity with IC(50) values of 280.8, 20.2, and 23.8μM,respectively. Values of binding energy obtained in a molecular docking study supported the results of enzymatic assays. More potent activity appeared to be associated with the presence of an apigenin moiety at position C-3' of flavones, as biflavone had an effect on 3CL(pro) inhibitory activity.

The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for discovery of drugs against SARS, because of its critical role in the viral life cycle. In this study, a natural compound called quercetin-3-beta-galactoside was identified as an inhibitor of the protease by molecular docking, SPR/FRET-based bioassays, and mutagenesis studies. Both molecular modeling and Q189A mutation revealed that Gln189 plays a key role in the binding. Furthermore, experimental evidence showed that the secondary structure and enzymatic activity of SARS-CoV 3CL(pro) were not affected by the Q189A mutation. With the help of molecular modeling, eight new derivatives of the natural product were designed and synthesized. Bioassay results reveal salient features of the structure-activity relationship of the new compounds: (1) removal of the 7-hydroxy group of the quercetin moiety decreases the bioactivity of the derivatives; (2) acetoxylation of the sugar moiety abolishes inhibitor action; (3) introduction of a large sugar substituent on 7-hydroxy of quercetin can be tolerated; (4) replacement of the galactose moiety with other sugars does not affect inhibitor potency. This study not only reveals a new class of compounds as potential drug leads against the SARS virus, but also provides a solid understanding of the mechanism of inhibition against the target enzyme.

The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for discovery of drugs against SARS, because of its critical role in the viral life cycle. In this study, a natural compound called quercetin-3-beta-galactoside was identified as an inhibitor of the protease by molecular docking, SPR/FRET-based bioassays, and mutagenesis studies. Both molecular modeling and Q189A mutation revealed that Gln189 plays a key role in the binding. Furthermore, experimental evidence showed that the secondary structure and enzymatic activity of SARS-CoV 3CL(pro) were not affected by the Q189A mutation. With the help of molecular modeling, eight new derivatives of the natural product were designed and synthesized. Bioassay results reveal salient features of the structure-activity relationship of the new compounds: (1) removal of the 7-hydroxy group of the quercetin moiety decreases the bioactivity of the derivatives; (2) acetoxylation of the sugar moiety abolishes inhibitor action; (3) introduction of a large sugar substituent on 7-hydroxy of quercetin can be tolerated; (4) replacement of the galactose moiety with other sugars does not affect inhibitor potency. This study not only reveals a new class of compounds as potential drug leads against the SARS virus, but also provides a solid understanding of the mechanism of inhibition against the target enzyme.

BACKGROUND:Epidemiologic studies have shown that dietary flavonoids reduce the risk of cardiovascular events. Onion is rich in quercetin, a strong antioxidant flavonoid. In some in vitro studies, quercetin improved endothelial function associated with atherosclerosis, a leading cause of cardiovascular events.

OBJECTIVE:The aim of this study was to determine whether chronic onion extract intake would improve postprandial endothelial dysfunction induced by an oral maltose load in healthy men.

METHODS:Healthy men (44±10 years, n=23) received 4.3 g of onion extract (containing 51 mg of quercetin) once a day for 30 days. Before and after the chronic onion extract intake, fasting and postprandial flow-mediated vasodilation (FMD) responses were measured.

RESULTS:Maltose loading significantly decreased FMD both before and after chronic onion extract intake (p=0.000037 and p=0.0035, respectively). The chronic onion extract intake did not significantly affect fasting FMD (p=0.069) but improved the postprandial FMD significantly from 5.1%±2.2% to 6.7%±2.6% (p=0.00015). The chronic onion extract intake did not alter systemic and forearm hemodynamics.

CONCLUSION:These findings suggest that chronic onion extract intake ameliorates postprandial endothelial dysfunction in healthy men and may be beneficial for improving cardiovascular health.

The purpose of this study was to evaluate the effect of chronic quercetin treatment on mitochondrial biogenesis, endurance exercise performance and activation levels of AMP-activated protein kinase (AMPK) in rat skeletal muscle. Rats were assigned to a control or quercetin group and were fed for 7 days. Rats treated with quercetin showed no changes in the protein levels of citrate synthase or cytochrome C oxidase IV or those of sirtuin 1, peroxisome proliferator-activated receptor gamma coactivator-1α or phosphorylated AMPK. After endurance swimming exercise, quercetin-treated rats demonstrated no differences in blood and muscle lactate levels or glycogen utilization speed compared to control rats. These results indicate that quercetin treatment does not stimulate mitochondrial biogenesis in skeletal muscle and does not influence metabolism in a way that might enhance endurance exercise capacity. On the other hand, the AMPK phosphorylation level immediately after exercise was significantly lower in quercetin-treated muscles, suggesting that quercetin treatment might provide a disadvantage to muscle adaptation when administered with exercise training. The molecular results of this study indicate that quercetin treatment may not be advantageous for improving endurance exercise performance, at least after high-dose and short-term therapy.

The effect of five propolis flavonoids on the infectivity and replication of some herpesvirus, adenovirus, coronavirus and rotavirus strains has been studied. Experiments were performed in vitro in cell cultures using the viral plaque reduction technique. The cytotoxicity of flavonoids, including chrysine, kaempferol, acacetin, galangin and quercetin, was evaluated on uninfected monolayers to determine their effect on cell growth and viability. Chrysine and kaempferol caused a concentration-dependent reduction of intracellular replication of herpes-virus strains when monolayers were infected and subsequently cultured in a drug-containing medium. However, virus infectivity was not significantly affected. Acacetin and galangin had no effect on either the infectivity or replication of any of the viruses studied. Quercetin reduced infectivity and intracellular replication, but only at the highest concentrations tested.

The effect of five propolis flavonoids on the infectivity and replication of some herpesvirus, adenovirus, coronavirus and rotavirus strains has been studied. Experiments were performed in vitro in cell cultures using the viral plaque reduction technique. The cytotoxicity of flavonoids, including chrysine, kaempferol, acacetin, galangin and quercetin, was evaluated on uninfected monolayers to determine their effect on cell growth and viability. Chrysine and kaempferol caused a concentration-dependent reduction of intracellular replication of herpes-virus strains when monolayers were infected and subsequently cultured in a drug-containing medium. However, virus infectivity was not significantly affected. Acacetin and galangin had no effect on either the infectivity or replication of any of the viruses studied. Quercetin reduced infectivity and intracellular replication, but only at the highest concentrations tested.

The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Recombinant 3CL(pro) was expressed in Pichia pastoris GS115 as a 42 kDa protein that displayed a K ( m ) of 15 ± 2 μM with Dabcyl-KTSAVLQSGFRKME-Edans as substrate. Purified 3CL(pro) was used for inhibition and kinetic assays with seven flavonoid compounds. The IC(50) of six flavonoidcompounds were 47-381 μM. Quercetin, epigallocatechin gallate and gallocatechin gallate (GCG) displayed good inhibition toward 3CL(pro) with IC(50) values of 73, 73 and 47 μM, respectively. GCG showed a competitive inhibition pattern with K ( i) value of 25 ± 1.7 μM. In molecular docking experiments, GCG displayed a binding energy of -14 kcal mol(-1) to the active site of 3CL(pro) and the galloyl moiety at 3-OH position was required for 3CL(pro) inhibition activity.

The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Recombinant 3CL(pro) was expressed in Pichia pastoris GS115 as a 42 kDa protein that displayed a K ( m ) of 15 ± 2 μM with Dabcyl-KTSAVLQSGFRKME-Edans as substrate. Purified 3CL(pro) was used for inhibition and kinetic assays with seven flavonoid compounds. The IC(50) of six flavonoidcompounds were 47-381 μM. Quercetin, epigallocatechin gallate and gallocatechin gallate (GCG) displayed good inhibition toward 3CL(pro) with IC(50) values of 73, 73 and 47 μM, respectively. GCG showed a competitive inhibition pattern with K ( i) value of 25 ± 1.7 μM. In molecular docking experiments, GCG displayed a binding energy of -14 kcal mol(-1) to the active site of 3CL(pro) and the galloyl moiety at 3-OH position was required for 3CL(pro) inhibition activity.

Nutrient levels in buckwheats that were maximized in day 8 sprouts (D8SP) included total phenolics, quercetin, and l-ascorbic acid, whereas those of oxalic, malic, tartaric, and citric acids, rutin, and gamma-aminobutyric acid (GABA) were found to reach maximum levels on day 10. Ethanolic extract of D8SP (2.5 mg/mL) revealed potent free-radical scavenging (FRS) and antioxidative (ANO) capabilities. However, its Fe2+-chelating capability was only moderate. To further study the hypolipidemic activity of D8SP, 36 Syrian hamsters were grouped into six groups and fed for 28 days, respectively, with (i) control meal, (ii) high fat plus high cholesterol meal, (iii) high fat plus high cholesterol plus 2.5% of buckwheat seeds, (iv) high fat plus high cholesterol plus 25% of buckwheat seeds, (v) high fat plus high cholesterol plus 2.5% of D8SP, and (vi) high fat plus high cholesterol plus 25% of D8SP. High seed meal prominently enhanced body weight gain, whereas high sprout meal exhibited the highest feed efficiency. Ratios of liver/body weight (L/B) were significantly lowered by all BS meals. Although low seed meal reduced serum total cholesterol (TC) levels (p<0.05), its effect was still inferior to the high seed and sprout meals (p<0.01). In contrast, serum triglyceride (TG) levels were lowered only by the high seed and sprout meals (p<0.05). Alternatively, levels of serum low-density lipoprotein cholesterol (LDL-C) were significantly suppressed by all buckwheat meals (p<0.01). Serum high-density lipoprotein cholesterol (HDL-C) levels were increased, however, insignificantly. Nutraceutically more meaningful is that both LDL-C/HDL-C and TC/HDL-C ratios were significantly lowered (p<0.01). Apparently, hepatic TC levels were significantly reduced, whereas hepatic TG levels were totally unaffected. Conclusively, sprouting triggers a variety of nutritional changes in buckwheats. Day 8 sprouts, consisting of high polyphenolic and moderate quercetin contents, are nutraceutically maximized when hypocholesterolemic, hypotriglyceridemic, and antioxidative activities are concerned.

The aim of this study was to characterize the polyphenolic compounds and antioxidant activity of cold-pressed seed oil from Finola cultivar of industrial hemp (Cannabis sativa L.). Several methodologies have been employed to evaluate the in vitro antioxidant activity of Finola hempseed oil (FHSO) and both lipophilic (LF) and hydrophilic fractions (HF). The qualitative and quantitative composition of the phenolic fraction of FHSO was performed by HPLC analyses. From the results is evident that FHSO has high antioxidative activity, as measured by DPPH radical (146.76 mmol of TE/100 g oil), inhibited β-carotene bleaching, quenched a chemically generated peroxyl radical in vitro and showed high ferrous ion chelating activity. Reactivity towards 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical cation and ferric-reducing antioxidant power valueswere 695.2 µmol of TE/100g oil and 3690.6 µmol of TE/100 g oil respectively. FHSO contains a significant amount of phenolic compounds of which 2780.4 mg of quercetin equivalent/100 g of total flavonoids. The whole oil showed higher antioxidant activity compared with LF and HF. Our findings indicate that the significant antioxidant properties shown from Finola seed oil might generally depend on the phenolic compounds, especially flavonoids, such as flavanones, flavonols, flavanols and isoflavones.

Nicotine is a potential inducer of oxidative stress, through which it can damage numerous biological molecules. The aim of our study was to investigate the prooxidative effects of nicotine and protective (additive or synergistic) effects of quercetin and vitamin C in the blood of experimental animals, to determine whether the combination of these antioxidants might be beneficial for clinical purposes. Wistar albino rats were receiving intraperitoneal nicotine injection (0.75 mg kg-1 per day) or saline (control group) or nicotine plus quercetin (40 mg kg-1 per day) and vitamin C (100 mg kg-1 per day) for three consecutive days. On day 4, we determined their blood lipid profile, liver enzymes, oxidative stress parameters, and antioxidative system parameters. Compared to untreated control, nicotine significantly increased total cholesterol, LDLcholesterol, triglycerides, liver enzymes (alanine transaminase, aspartate transaminase, and lactate dehydrogenase) and oxidative stress parameters (superoxide anion, hydrogen peroxide, and lipid peroxide) and decreased HDL-cholesterol, glutathione, and superoxide dismutase/catalase activity. Quercetin + vitamin C reversed these values significantly compared to the nicotine alone group. Our results confirm that nicotine has significant prooxidative effects that may disrupt the redox balance and show that the quercetin + vitamin C combination supports antioxidant defence mechanisms with strong haematoprotective activity against nicotine-induced toxicity. In practical terms, this means that a diet rich in vitamin C and quercetin could prevent nicotine-induced toxicity and could also be useful in the supportive care of people exposed to nicotine.

BACKGROUND:On the base of our previous study we were observed relevant studies on the hypothesis that the antiviral activity of quercetin 7-rhamnoside (Q7R), a flavonoid, won't relate ability of its antioxidant.

METHODS:We were investigated the effects of Q7R on the cytopathic effects (CPE) by CPE reduction assay. Production of DNA fragment and reactive oxygen species (ROS) induced by PEDV infection were studied using DNA fragmentation assay and flow cytometry.

RESULTS:In the course of this study it was discovered that Q7R is an extremely potent compound against PEDV. The addition of Q7R to PEDV-infected Vero cells directly reduced the formation of a visible cytopathic effect (CPE). Also, Q7R did not induce DNA fragmentation. Furthermore, ROS increased the infection of PEDV, which was strongly decreased by N-acetyl-L-cysteins (NAC). However, the increased ROS was not decreased by Q7R. Antiviral activity of antioxidants such as NAC, pyrrolidine dithiocarbamate (PDTC), and the vitamin E derivative, trolox, were hardly noticed.

CONCLUSIONS:We concluded that the inhibition of PEDV production by Q7R is not simply due to a general action as an antioxidants and is highly specific, as several other antioxidants (NAC, PDTC, trolox) are inactive against PEDV infection.