ascorbic-acid and hesperetin

Blond orange juice is the most consumed fruit juice in the world. It is a source of hesperidin, a bioavailable flavonoid reported to exhibit potential vascular protective actions. However, the specific impact on vascular function of Citrus phytomicronutrients, is unknown. For the first time, we investigated the effects of blond orange juice compared with a control beverage mimicking the composition of orange juice (including Vitamin C but no phytomicronutrients), on antioxidant markers, cardiovascular risk factors and endothelial function.. Twenty five male volunteers with two cardiovascular risk factors (age over 50 years and LDL-cholesterol between 130 and 190 mg/L) were enrolled in a randomized cross-over study. They received 3 times daily 200 mL of either blond orange juice or control beverage for 4 weeks, spaced by a 5-week wash-out. Endothelial function (flow mediated dilatation and plasma markers), oxidative status, lipid profile and inflammatory markers were assessed.. Daily intakes of orange juice significantly led to a marked antioxidant effect which was correlated to hesperetin plasma levels and related with a decrease in reactive oxygen species. A tendency towards reduction of endothelial dysfunction and modest increase in plasma apoA-I concentration were also observed. This allows further experiments demonstrating the specific effect of phytomicronutrients from orange juice.. These findings suggest that daily intake of nutritionally relevant dose of blond orange juice may contribute for a significant antioxidant effect through the phytochemicals contained in. Orange juice may be associated to other healthy foods to achieve a significant effect on the vascular function. This study is recorded in ClinicalTrials.com as NCT00539916.

Topics: Antioxidants; Apolipoprotein A-I; Ascorbic Acid; Biomarkers; Body Mass Index; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Citrus sinensis; Cross-Over Studies; Flavonoids; Fruit and Vegetable Juices; Hesperidin; Humans; Hypercholesterolemia; Male; Middle Aged; Oxidative Stress; Phytochemicals; Reactive Oxygen Species; Risk Factors; Single-Blind Method; Triglycerides

Cataracts are a major cause of blindness worldwide. As anti‑cataract pharmaceutical therapies require long‑term treatment, identifying anti‑cataract compounds that are ubiquitous in the human diet, have no adverse effects and are affordable, is of paramount importance. The present study focused on hesperetin and its derived compounds, hesperetin stearic acid ester (Hes‑S) and hesperetin oleic acid ester (Hes‑O), in order to investigate their therapeutic potential to treat cataracts in a selenite animal model. Thirteen‑day‑old Sprague Dawley rats were divided into 12 groups. Animals in groups 1 and 7 were subcutaneously injected with vehicle, those in groups 2 and 8 were administered hesperetin, those in groups 3 and 9 received stearic acid, those in groups 4 and 10 were injected with oleic acid, those in groups 5 and 11 were administered Hes‑S, and those in groups 6 and 12 received Hes‑O (10 nmol/kg body weight on days 0, 1 and 2). Animals in groups 7 to 12 were treated with sodium selenite (20 µmol/kg body weight given 4 h following the test compound treatment on day 0) to induce cataract. On day 6, rats had less severe central opacities and lower stage cataracts than rats in the selenite treatment‑only control groups. The levels of glutathione (GSH) and ascorbic acid (AsA) in lenses with selenite‑induced cataracts declined to one‑third of that of controls, and the reduction in GSH and AsA levels was rescued following hesperetin, Hes‑S or Hes‑O treatment, with concentrations remaining to 70‑80% of that of controls. However, there were no changes in the plasma levels of GSH and AsA following treatments. Administration of either hesperetin or hesperetin‑derived compounds prevented the reduction of chaperone activity in the lens, and rats treated with Hes‑S or Hes‑O treatment had significantly greater chaperone activity than hesperetin‑treated rats. Collectively, these results suggested that hesperetin and hesperetin‑derived compounds may be novel drug compounds that have the potential to prevent or delay the onset of cataracts.

Topics: Animals; Ascorbic Acid; Cataract; Female; Glutathione; Hesperidin; Rats; Rats, Sprague-Dawley; Selenious Acid

Systematic screening for optimal formulation composition and production parameters for nanosuspensions consumes a lot of time and also drug material when performed at lab scale. Therefore, a cost-effective miniaturized scale top down approach for nanocrystals production by wet bead milling was developed. The final set-up consisted of 3 magnetic stirring bars placed vertically one over the other in a 2 mL glass vial and agitated by a common magnetic stirring plate. All of the tested actives (cyclosporin A, resveratrol, hesperitin, ascorbyl palmitate, apigenin and hesperidin) could be converted to nanosuspensions. For 4 of them, the particles sizes achieved were smaller than previously reported on the literature (around 90 nm for cyclosporin A; 50 nm for hesperitin; 160 nm for ascorbyl palmitate and 80 nm for apigenin). The "transferability" of the data collect by the miniaturized method was evaluated comparing the production at larger scale using both wet bead milling and high pressure homogenization. Transferable information obtained from the miniaturized scale is minimum achievable size, improvements in size reduction by reduction of beads size, diminution kinetics and potentially occurring instabilities during processing. The small scale batches also allow identification of optimal stabilizer types and concentrations. The batch size is 0.5 mL, requiring approximately 50 mg or 5 mg of drug (5% and 1% suspension, respectively). Thus, a simple, accessible, low-cost miniaturized scale method for the production of pharmaceutical nanocrystals was established.

Topics: Apigenin; Ascorbic Acid; Chemistry, Pharmaceutical; Cyclosporine; Hesperidin; Miniaturization; Nanoparticles; Particle Size; Resveratrol; Stilbenes; Suspensions; Technology, Pharmaceutical

This study investigated the ability of hesperetin, a natural flavonoid, to prevent selenite-induced cataracts in a rat model.. Animals were divided into four treatment groups: G1 (control group), G2 (hesperetin-treated group), G3 (selenite-induced cataract group), and G4 (hesperetin-treated selenite cataract group). Animals in the G1 and G3 groups were injected with vehicle alone, while those in the G2 and G4 groups received a subcutaneous injection of hesperetin (0.4 μg/g bodyweight on days 0, 1, and 2, corresponding to P13, P14, and P15). Sodium selenite (20 μmol/g bodyweight given 4 h after the hesperetin injection on day 0) was administered to rats in the G3 and G4 groups to induce cataract formation. Lenses were observed with slit-lamp microscopy, and filensin degradation and the decreased glutathione (GSH) and ascorbic acid levels in the lens were measured on day 6.. Lenses in the G3 group showed mature central opacity, while some lenses in the G4 group lacked central opacity and had lower-grade cataracts. All lenses in the G1 and G2 groups were transparent. Expression of the 94 kDa and 50 kDa forms of filensin was significantly decreased in the lenses in the G3 group compared with those in the G1 and G2 groups. Interestingly, these forms of filensin rescued the rat lenses in the G4 group. In the G3 group lenses, the GSH and ascorbic acid levels were lower than in the control group but were normalized in the G4 group lenses.. The results suggest that hesperetin can prevent selenite-induced cataract formation.

Topics: Animals; Antioxidants; Ascorbic Acid; Cataract; Disease Models, Animal; Eye Proteins; Female; Free Radical Scavengers; Glutathione; Hesperidin; Intermediate Filament Proteins; Lens, Crystalline; Oxidative Stress; Proteolysis; Rats; Rats, Sprague-Dawley; Sodium Selenite

Cadmium (Cd) is ubiquitous in the environment and exposure through food and water as well as occupational sources can contribute to a well-defined spectrum of disease. The present study was undertaken to evaluate the role of hesperetin (Hp) in alleviating the Cd induced biochemical changes in rats.. During the experiment, male Wistar rats were injected with Cd 83 mg/kg day) subcutaneously alone or with oral administration of Hp 840 mg/kg day) for 21 days.. In Cd treated rats the levels of plasma lipid peroxidation (LPO) markers: thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH) were significantly increased while the levels of plasma non-enzymatic antioxidants: reduced glutathione (GSH), vitamins C and E were significantly decreased in Cd administered rats. Administration of Hp along with Cd significantly decreased the level of LPO markers with elevation of non-enzymatic antioxidants in plasma. In vitro studies on the effect of Hp on scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH*), 2,2-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS+), superoxide anion (O*-), hydroxyl (OH*) radicals and reducing power also confirmed the free radical scavenging and antioxidant activity of Hp. In addition to that, ascorbic acid, butylated hydroxyl toluene was used as the reference antioxidant radical scavenger compounds. Thus, the observed effects are due to the free radical scavenging and antioxidant potential of Hp. Interestingly, among the different concentrations, tested 50 microM of Hp showed the highest antioxidant and free radical scavenging activities when compared to other concentrations.. The result of these findings provides further evidence to the neutraceutical and pharmaceutical potentials of Hp.

Topics: Administration, Oral; Animals; Antioxidants; Ascorbic Acid; Benzothiazoles; Biomarkers; Biphenyl Compounds; Cadmium Chloride; Dose-Response Relationship, Drug; Environmental Pollutants; Glutathione; Hesperidin; Hydroxyl Radical; Injections, Subcutaneous; Lipid Peroxidation; Lipid Peroxides; Male; Oxidative Stress; Picrates; Rats; Rats, Wistar; Sulfonic Acids; Thiobarbituric Acid Reactive Substances; 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