ascorbic-acid and naringenin

Heterologous expression of genes involved in the biosynthesis of various products is of increasing interest in biotechnology and in drug research and development. Microbial cells are most appropriate for this purpose. Availability of more microbial genomic sequences in recent years has greatly facilitated the elucidation of metabolic and regulatory networks and helped gain overproduction of desired metabolites or create novel production of commercially important compounds. Saccharomyces cerevisiae, as one of the most intensely studied eukaryotic model organisms with a rich density of knowledge detailing its genetics, biochemistry, physiology, and large-scale fermentation performance, can be capitalized upon to enable a substantial increase in the industrial application of this yeast. In this review, we describe recent efforts made to produce commercial secondary metabolites in Saccharomyces cerevisiae as pharmaceuticals. As natural products are increasingly becoming the center of attention of the pharmaceutical and nutraceutical industries, such as naringenin, coumarate, artemisinin, taxol, amorphadiene and vitamin C, the use of S. cerevisiae for their production is only expected to expand in the future, further allowing the biosynthesis of novel molecular structures with unique properties.

Topics: Artemisinins; Ascorbic Acid; Coumaric Acids; Drug Industry; Flavanones; Lactones; Paclitaxel; Pharmaceutical Preparations; Polycyclic Sesquiterpenes; Saccharomyces cerevisiae; Sesquiterpenes

A series of naringenin derivatives were designed and synthesized as multifunctional anti-Alzheimer's disease (AD) agents. The results showed that these derivatives displayed moderate-to-good acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities at the micromolar range (IC

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Animals; Butyrylcholinesterase; Carbamates; Chelating Agents; Cholinesterase Inhibitors; Drug Design; Electrophorus; Flavanones; Free Radical Scavengers; Horses; Kinetics; Molecular Docking Simulation; Molecular Structure; Peptide Fragments; Protein Binding; Protein Multimerization; Structure-Activity Relationship

Whole fruit and vegetable consumption is universally promoted as healthy, to a large extent due to their high contents of phytochemicals, including phenolics and dietary fibre. The major fibre in fruits and vegetables, pectin, however also decreases the bioavailability of phenolics and carotenoids. While ascorbic acid, sucrose and olive oil lipids may increase the bioavailability of various phenolics, their effects in the presence of pectin have not been investigated. This study aimed to evaluate the modulating effects of sucrose (5.0%), ascorbic acid (0.1%) and olive oil (2.5%) on the inhibition by pectin (2.0%) of ferulic acid and naringenin bioaccessibility and Caco-2 cellular uptake. Pectin reduced the bioaccessbility of ferulic acid and naringenin, by 45 and 65%, respectively. Sucrose mitigated the inhibitory effect of pectin and increased naringenin bioaccessbility from 7.9 to 15.0%. When added to digestions with ferulic acid and pectin, sucrose and olive oil totally negated pectin's bioaccessibility inhibition. The Caco-2 cellular uptake of bioaccessible ferulic acid was high (58.3%) and pectin and ascorbic acid together increased it to 85.6%. The Caco-2 cellular uptake of bioaccessible naringenin was also high (47.0%) and pectin increased it to 95.0%. Sucrose and olive oil for ferulic acid and only sucrose for naringenin totally negated the inhibitory effect of pectin on the overall in vitro availability (cellular uptake as percentage of amount of phenolic initially digested). The ameliorating effects of sucrose and olive oil are due to substantially increased bioaccessibility of the phenolics, probably due reduced encapsulation of the phenolics in pectin.

Topics: Ascorbic Acid; Biological Availability; Biological Transport; Caco-2 Cells; Coumaric Acids; Flavanones; Humans; Lipids; Olive Oil; Pectins; Sucrose

Previously, we reported that alcoholic fermentation enhanced flavanones and carotenoids content of orange juice. The aim of this work was to evaluate the influence of pasteurization on the qualitative and quantitative profile of bioactive compounds and the antioxidant capacity of fermented orange juice. Ascorbic acid (203 mg/L), total flavanones (647 mg/L), total carotenoids (7.07 mg/L) and provitamin A (90.06 RAEs/L) values of pasteurized orange beverage were lower than those of fermented juice. Total phenolic remained unchanged (585 mg/L) and was similar to that of original juice. The flavanones naringenin-7-O-glucoside, naringenin-7-O-rutinoside, hesperetin-7-O-rutinoside, hesperetin-7-O-glucoside and isosakuranetin-7-O-rutinoside, and the carotenoids karpoxanthin and isomer, neochrome, lutein, ζ-carotene, zeaxanthin, mutatoxanthin epimers, β-cryptoxanthin and auroxanthin epimers were the major compounds. Pasteurization produced a decrease in antioxidant capacity of fermented juice. However, TEAC (5.45 mM) and ORAC (6353 μM) values of orange beverage were similar to those of original orange juice. The novel orange beverage could be a valuable source of bioactive compounds with antioxidant capacity and exert potential beneficial effects.

Topics: Antioxidants; Ascorbic Acid; Carotenoids; Citrus sinensis; Evaluation Studies as Topic; Fermentation; Flavanones; Flavonoids; Food Handling; Fruit; Fruit and Vegetable Juices; Glucosides; Hesperidin; Hot Temperature; Pasteurization; Phenols; Provitamins; Vitamin A

Iron is a component of several metalloproteins involved in crucial metabolic processes such as oxygen sensing and transport, energy metabolism, and DNA synthesis. This metal progressively accumulates in the pathogenesis of Alzheimer's (AD) and Parkinson's (PD) diseases. Naringenin (NGEN), a natural flavonoid compound, has been reported to possess neuroprotective effect against PD-related pathology, however, the mechanisms underlying its beneficial effects are poorly defined. Thus, the aim of this study is to investigate the potential mechanism involved in the cytoprotection of NGEN against iron-induced neurotoxicity in the cerebral cortex of Wistar rats. Animals that were given repetitive injections of iron dextran for a total of 4 weeks showed a significant increase in lipid and protein markers such as thiobarbituric reactive acid substances, protein carbonyl product content levels, and DNA apoptosis in the cerebral cortex. These changes were accompanied by a decrease of enzymatic antioxidants like superoxide dismutase and catalase and in the levels of nonenzymatic antioxidants like total thiols and ascorbic acid. The activity of glutathione peroxidase remained unchanged in rats. A significant decrease in acetylcholinesterase and Na(+)/K(+)-ATPase activities was also shown, with a substantial rise in the nitric oxide levels. Coadministration of NGEN to iron-treated rats significantly improved antioxidant enzyme activities and attenuated oxidative damages observed in the cerebral cortex. The potential effect of NGEN to prevent iron-induced neurotoxicity was also reflected by the microscopic study, indicative of its neuroprotective effects.

Topics: Acetylcholinesterase; Animals; Apoptosis; Ascorbic Acid; Catalase; Cerebral Cortex; DNA Fragmentation; Flavanones; Iron Overload; Male; Neuroprotective Agents; Neurotoxicity Syndromes; Oxidative Stress; Protein Carbonylation; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Based on the previous result, several naringenin derivatives modified at position 7 with bulky substituents were designed and synthesized, and their inhibitory effects on HCT116 human colon cancer cells were tested using a clonogenic assay. The half maximal inhibitory concentrations (IC(50)) of five naringenin derivatives ranged between 1.20 μM and 20.01 μM which are much better than naringenin used as a control. In addition, new structural modification at C-4 of flavanone results in improving both the anti-cancer effect and anti-oxidative effect. In vitro cyclin dependent kinase 2 (CDK2) binding assay was carried out based on the previous results. To elucidate the possible interaction between naringenin derivatives and CDK2, in silico docking study was performed. This result demonstrates the rationale for the different inhibitory activities of the naringenin derivatives. These findings could be used for designing cancer therapeutic or preventive flavanone-derived agents.

Topics: Binding Sites; Cell Survival; Colonic Neoplasms; Cyclin-Dependent Kinase 2; Drug Design; Flavanones; HCT116 Cells; Humans; Molecular Docking Simulation; Protein Binding; Protein Structure, Tertiary

Phytochemical stability was studied in dried tomato pulp and dried tomato peel stored at 30 °C with various water activity (a(w)) levels and related to glass transition temperature (T(g)) and water mobility. At a(w) < 0.32, the values for T(g) were >30 °C for both the pulp and peel, indicating that they were in the glassy state, with little molecular mobility. At a(w) = 0.56, T(g) was <30 °C, indicating the samples were in the rubbery state, with decreased viscosity and increased molecular mobility. The hydrophilic antioxidants (hydroxycinnamic acids and naringenin) were stable for samples in the glassy state, but were unstable for samples in the rubbery state. In contrast, the lipophilic antioxidants lycopene and α-tocopherol were mostly unstable for samples in the glassy state. These results could be used to optimize phytochemical contents in tomato products that must be dried prior to further processing.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; Calorimetry, Differential Scanning; Carotenoids; Chromatography, High Pressure Liquid; Color; Coumaric Acids; Desiccation; Flavanones; Food Handling; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Lycopene; Magnetic Resonance Spectroscopy; Rutin; Solanum lycopersicum; Transition Temperature; Water

Tumor cells are able to survive and proliferate in spite of their increased oxidative stress. This was taken as a hint for the implication of oxidants/antioxidants in the proliferation of glial-tumor cells. In the present study, an anti-proliferative effect of Naringenin, an antioxidant against cerebrally implanted C6 glioma cells in rats has been investigated. The status of lipid peroxidation/antioxidants, expressions of protein kinase C, nuclear factor κB, cyclin D1, cyclin dependent kinase 4, proliferating cell nuclear antigen, vascular endothelial growth factor, argyophillic nucleolar organizing regions and histopathology of brain tissues of control and experimental rats were analyzed. On supplementation of naringenin (50mg/kg BW for 30 days) to glioma induced rats, there was a reduction in lipid peroxidation with an increased antioxidant status. There was a significant decrease in the expressions of protein kinase C, nuclear factor κB, cyclin D1 and cyclin dependent kinase 4 on naringenin treatment. Further, the drug could modulate the glial-tumor cell proliferation as evidenced from the histopathological findings, argyophillic nucleolar organizing regions staining, proliferating cell nuclear antigen and vascular endothelial growth factor immunostaining. The findings suggest that naringenin could underlie the inhibition of glial tumor cell proliferation in C6 glioma models of rat.

Topics: Animals; Antioxidants; Ascorbic Acid; Brain Neoplasms; Cell Growth Processes; Cell Line, Tumor; Cyclin D1; Cyclin-Dependent Kinase 4; Flavanones; Glioma; Glutathione; Glutathione Peroxidase; Immunohistochemistry; Male; NF-kappa B; Proliferating Cell Nuclear Antigen; Protein Kinase C; Rats; Receptors, Peptide; Thiobarbituric Acid Reactive Substances; Vascular Endothelial Growth Factor A; Vitamin E

Cadmium (Cd)-induced oxidative stress and hepatic injury is one of the major outcomes of chronic Cd toxicity, which can be ameliorated by numerous antioxidants. The present study was undertaken to find the therapeutic efficacy of naringenin (NGN) plus vitamins C and E on Cd-induced oxidative hepatotoxicity in Wistar rats. It has been noticed that Cd intoxication significantly elevates the levels of serum hepatic marker enzymes such as alanine amino transferase, aspartate amino transferase, alkaline phosphatase, lactate dehydrogenase, γ glutamyl transferase, total bilirubin, and hepatic thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes and protein carbonyls. In addition, Cd also decreases the activities of hepatic enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and glucose-6-phosphate dehydrogenase and the levels of non-enzymatic antioxidants total sulphydryl groups, reduced glutathione, vitamins C and E and histopathological changes in liver. Treatment with NGN and vitamins C and E in combination more significantly improved the altered biochemical and histopathological changes in the liver of Cd-intoxicated rats than the NGN or vitamins C and E treatment alone.. The present data suggest that combined administration of NGN with vitamins C and E proved to be more beneficial in the treatment of Cd-hepatotoxicity than NGN treatment alone.

Topics: Animals; Antioxidants; Ascorbic Acid; Cadmium; Chemical and Drug Induced Liver Injury; Citrus; Drug Therapy, Combination; Flavanones; Liver; Male; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Vitamin E; Vitis

A capillary electrophoresis with electrochemical detection was developed for the simultaneous determination of three flavonoids (naringenin, rutin, quercetin) and ascorbic acid. It was found that naringenin, rutin, quercetin and ascorbic acid were well separated within 5 min in borate buffer solution (pH 8.6, 24 mM). The detection limit was 1.0 microM for naringenin, 8.0 microM for rutin, 2.0 microM for ascorbic acid and 0.5 microM for quercetin. The protocol was successfully applied for the determination of the analytes in rat serum and excrement. Recovery results ranged from 90.9 to 108.6%.

Topics: Animals; Ascorbic Acid; Buffers; Electrochemistry; Electrodes; Electrophoresis, Capillary; Feces; Flavanones; Flavonoids; Hydrogen-Ion Concentration; Limit of Detection; Quercetin; Rats; Reproducibility of Results; Rutin; Time Factors

Macrophages and microglia are thought to account for initial disease progression in acute myocardial infarction and acute ischemic stroke. Before our study, the inhibitory effects of naringenin, a flavonoid, on lipopolysaccharide (LPS)-induced inflammation in macrophages and microglia have not been fully reported and compared. We hypothesized that naringenin can effectively inhibit LPS-induced inflammation of macrophages and microglia at different concentrations, the range of which is broader, with the lowest concentration more easily achieved in macrophages. In this study, we compared the anti-inflammatory effects of naringenin on LPS-stimulated RAW 274.6 macrophages and BV2 microglia and the suppression effects of naringenin and vitamin C (a well-known anti-inflammatory agent) on LPS-induced nitrite production. The results show that macrophages could maintain cell viability at higher naringenin concentrations and were more easily activated by LPS in comparison to microglia (200 vs 100 μmol/L; 0.1 vs 1 μg/mL). Under LPS (1 μg/mL) stimulation in both cell types, naringenin (up to 200 μmol/L in macrophages and 100 μmol/L in microglia) inhibited nitrite production and inducible nitric oxide synthase and cyclooxygenase-2 expression in a dose-dependent manner. The range of naringenin concentrations for inhibition was broader, and the lowest concentration was more easily achieved in macrophages; the lowest effective concentrations of naringenin to achieve constant suppression effect were 50 μmol/L in macrophages and 100 μmol/L in microglia, respectively. Vitamin C (100 μmol/L), compared with naringenin (100 μmol/L), had less and no suppression effect on LPS (1 μg/mL)-induced nitrite production in macrophages and microglia, respectively. In conclusion, naringenin more effectively inhibits the LPS-induced inflammatory status, including nitrite production and inducible nitric oxide synthase and cyclooxygenase-2 expression, in macrophages than in microglia. The findings of the present study suggest that consumption of naringenin-containing flavonoids might be beneficial to the cardiovascular and cerebrovascular inflammatory process.

Topics: Animals; Anti-Inflammatory Agents; Ascorbic Acid; Cell Survival; Citrus; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Flavanones; Lipopolysaccharides; Macrophages; Mice; Microglia; Nitric Oxide Synthase Type II; Nitrites; Plant Extracts

The aim was to study the effect of naringenin, a biologically active compound, on tissue antioxidant status and lipid peroxidation in ethanol-induced hepatotoxicity in rats.. Rats were divided into four groups: Groups 1 and 2 received isocaloric glucose and 0.5% carboxymethyl cellulose; groups 3 and 4 received 20% ethanol equivalent to 6 g/kg daily for 60 days. In addition, groups 2 and 4 were given naringenin (50 mg/kg) daily for the last 30 days of the experiment.. The results showed significantly elevated levels of serum aspartate and alanine transaminases, gamma-glutamyl transpeptidase, tissue thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and protein carbonyl content, and significantly lowered activities/levels of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione and vitamins C and E in ethanol-treated rats compared with control rats. Administration of naringenin to rats with ethanol-induced liver injury significantly decreased the levels of serum aspartate and alanine transaminases, gamma-glutamyl transpeptidase, tissue thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and protein carbonyl content and significantly elevated the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase, and the levels of reduced glutathione and vitamins C and E in the tissues compared with unsupplemented ethanol-treated rats. Histological changes observed in the liver correlated with the biochemical findings.. Taken together these findings suggest that naringenin has a therapeutic potential in the abatement of ethanol-induced hepatotoxicity.

Topics: Animals; Antioxidants; Ascorbic Acid; Biological Products; Disease Models, Animal; Flavanones; Heart; Kidney; Lipid Peroxidation; Liver Cirrhosis, Alcoholic; Male; Myocardium; Oxidative Stress; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Time Factors; Vitamin E

Chronic exposure to oxidative stress especially to highly reactive hydroxyl radicals (HO*) could damage biomolecules, particularly DNA, that in turn would accelerate onset of degenerative diseases. In the present study a few standard phytochemicals (vitamin C, gallic acid, catechin, apigenin, naringenin and naringin) and plant extracts (Hippophae rhamnoides kernel (HRK), Syzygium cumini kernel (SCK) and Punica granatum pericarp (PGP)) were evaluated for their potential to protect/damage DNA in Fenton's system using in vitro models. The results indicated a significant DNA protective effect for naringin and PGP whereas other phytochemicals/extracts showed DNA damaging effect similar to or more than that of control value. The phytochemicals/extracts were also evaluated for their antioxidant and iron chelation properties. In general, the phytochemicals/extracts with high antioxidant activity but without iron chelation capacity failed to protect DNA in Fenton's system, suggesting that iron chelation was an essential requirement for the phytochemicals studied here to retard HO* generation by Fenton's reaction. This was demonstrated by the high iron chelation capacity of naringin and PGP (83.67% and 68.67% respectively) and their DNA protective effect. Commonly consumed phytochemicals such as vitamin C and gallic acid with their high reducing power and at higher physiological concentration, could regenerate free iron for Fenton's reaction leading to DNA damage as shown here.

Topics: Antioxidants; Apigenin; Ascorbic Acid; Bacteriophage lambda; Catechin; Cytoprotection; DNA Damage; DNA Fragmentation; Dose-Response Relationship, Drug; Flavanones; Gallic Acid; Genomic Instability; Hydrogen Peroxide; In Vitro Techniques; Iron; Models, Biological; Plant Extracts

Lutein is assumed to protect the human retina from blue light and oxidative stress and diminish the incidence of age-related macular degeneration. This antioxidant is commonly ingested with other dietary antioxidants. The aim of the present study was to assess whether the main dietary antioxidants, i.e. carotenoids, polyphenols and vitamins C and E, affect lutein absorption. We measured the effect of adding a mixture of antioxidants (500 mg vitamin C, 67 mg (100 IU) vitamin E and 1 g polyphenols) to a lutein-containing meal (18 mg) on the postprandial lutein response in the chylomicron-rich fraction in eight healthy men. Lutein response was weakest (-23 %; P=0 x 07) after ingestion of the meal containing antioxidants (21 x 9 (sem 4 x 6) v. 28 x 4 (sem 7 x 2) nmol x h/l). To assess the effect of each class of antioxidants and potential interactions, we subsequently evaluated the effect of various combinations of antioxidants on lutein uptake by human intestinal Caco-2 TC-7 cells. A full factorial design showed that both a mixture of polyphenols (gallic acid, caffeic acid, (+)-catechin and naringenin) and a mixture of carotenoids (lycopene plus beta-carotene) significantly (P<0 x 05) impaired lutein uptake by (-10 to-30 %), while vitamins C and E had no significant effect. Subsequent experiments showed that the aglycone flavanone naringenin was the only polyphenol responsible for the effect of the polyphenol mixture, and that the carotenoid effect was not carotenoid species-dependent. Taken together, the present results suggest that lutein absorption is not markedly affected by physiological concentrations of vitamins C and E but can be impaired by carotenoids and naringenin

Topics: Adult; Antioxidants; Ascorbic Acid; Biological Availability; Caco-2 Cells; Carotenoids; Chromatography, High Pressure Liquid; Chylomicrons; Diet; Flavanones; Flavonoids; Humans; Intestinal Absorption; Lutein; Male; Nutritional Physiological Phenomena; Phenols; Polyphenols; Postprandial Period; Triglycerides; Vitamin E

The aim of this study was to investigate the effect of naringenin on oxytetracycline-induced nephrotoxicity in rats. Oxytetracycline (200 mg/kg body weight, ip) was administered in 0.5 ml of sterile physiological saline for 15 days, resulting in a significant increase in serum urea and creatinine and reduction in creatinine clearance. A significant increase in lipid peroxidation markers (TBARS and lipid hydroperoxide) and decrease in antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and low molecular weight antioxidants (vitamin C, vitamin E, and reduced glutathione) levels were also observed in oxytetracycline-treated rats. The oral administration of naringenin (50 mg/kg body weight) attenuated the oxytetracycline-induced nephrotoxicity by significantly decreased levels of serum urea and creatinine with the significant normalization of creatinine clearance. Upon the administration of naringenin, the depleted renal antioxidant defense system (enzymatic and non-enzymatic antioxidants) was significantly increased in rats treated with oxytetracycline. These biochemical observations were supplemented by histopathological examination of kidney section. The present results suggest that the supplementation of naringenin might be helpful to alleviate the oxytetracycline-induced oxidative injury in kidney.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; Catalase; Creatinine; Drug Interactions; Flavanones; Glutathione Peroxidase; Injections, Intraperitoneal; Kidney; Lipid Peroxidation; Male; Molecular Structure; Oxytetracycline; Random Allocation; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Urea; Vitamin E

The antioxidant properties of freeze-dried citrus fruit peels (orange, lemon, grapefruit) and methanolic extracts from the peel were studied. Freeze-dried orange peel showed the highest, lemon peel somewhat less and grapefruit peel the lowest but still remarkable antioxidant activity. This could be significantly improved by preparing methanolic extracts of the peels. Comparative examinations and autoxidation studies with the flavanon glycosides hesperidin and naringin as well as with their aglycones hesperetin and naringenin showed that the former are mainly responsible for the antioxidative activity of the citrus peel and extracts. In order to compare their antioxidative activity with that of the commercially available natural antioxidants alpha-tocopherol and ascorbylpalmitate, the freeze-dried citrus peels and their methanolic extracts should be used in higher concentrations, in consideration of their peculiar properties and complex natural composition. Furthermore, aspects of the correlation between antioxidant activity and molecular structure of the flavanones were discussed.

Topics: Antioxidants; Ascorbic Acid; Citrus; Flavanones; Flavonoids; Freeze Drying; Hesperidin; Vitamin E