Hesperidin, which is the most abundant flavonoid of Citrus unshiu (Rutaceae), has been reported to possess diverse activities and widely used as functional foods and cosmetics. For the development of functional products, extraction procedure is indispensable. Extraction conditions affect the composition of extract as well as its biological activity. Therefore, we tried to optimize extraction conditions such as extraction solvent, extraction time and extraction temperature for maximum yield of hesperidin using response surface methodology with threelevel-three-factor Box-Behnken design (BBD). Regression analysis showed a good fit of the experimental data and the optimal condition was obtained as ethanol concentration, 59.0%; temperature 71.5degrees C and extraction time, 12.4 h. The hesperidin yield under the optimal condition was found to be 287.8 microg per 5 mg extract, which was well matched with the predicted value of 290.5 microg. These results provides optimized extraction condition for hesperidin and might be useful for the development of hesperidin as functional products like health supplements, cosmetics and medicinal products.
Citrus* ; Ethanol ; Functional Food ; Hesperidin*

Hesperetin (3',5,7-trihydroxy 4'-methoxyflavanone) and its glycoside hesperidin (hesperetin 7-rhamnoglucoside) in oranges have been reported to possess pharmacological effects related to anti-obesity. However, hesperetin and hesperidin have not been studied on suppressive effects on appetite. This study examined that hesperetin and hesperidin can stimulate the release of cholecystokinin (CCK), one of appetite-regulating hormones, from the enteroendocrine STC-1 cells, and then examined the mechanisms involved in the CCK release. Hesperetin significantly and dose-dependently stimulated CCK secretion with an EC50 of 0.050 mM and increased the intracellular Ca2+ concentrations ([Ca2+]i) compared to the untreated control. The stimulatory effect by hesperetin was mediated via the entry of extracellular Ca2+ and the activation of TRP channels including TRPA1. These results suggest that hesperetin can be a candidate biomolecule for the suppression of appetite and eventually for the therapeutics of obesity.
Appetite ; Cholecystokinin* ; Citrus sinensis ; Enteroendocrine Cells ; Hesperidin ; Obesity

Aqueous extraction of Citrus unshiu peels (AECUP) is mainly comprised with pro-angiogenichesperidin and narirutin. In this study, we report approaches to increasing the yields of extracted hesperidin and narirutinfrom Citrus unshiu peels using proper solvents. Significantly improved yields of both compounds were obtained using methanol and dimethyl sulfoxide (DMSO) compared to acetonitrile, ethyl acetate, ethanol, and isopropyl alcohol. Especially, effect of DMSO was by far the better of the two solvents in extraction of hesperidin. In addition, the DMSO extracted hesperidin significantly induced the pro-angiogenic effects of human umbilical vein endothelial cells (HUVECs) and markedly up-regulated phosphorylation of the ERK1/2 signaling pathway. These results demonstrate that pro-angiogenic inducer; hesperidin and narirutin can be simply, easily, and effectively extracted from Citrus unshiu peels.
2-Propanol ; Citrus* ; Dimethyl Sulfoxide* ; Ethanol ; Hesperidin ; Human Umbilical Vein Endothelial Cells ; Methanol ; Phosphorylation ; Solvents

OBJECTIVES: Hydrogen peroxide (H2O2) surface treatment of fiber posts has been reported to increase bond strength of fiber posts to resin cements. However, residual oxygen radicals might jeopardize the bonding procedure. This study examined the effect of three antioxidant agents on the bond strength of fiber posts to conventional and self-adhesive resin cements. MATERIALS AND METHODS: Post spaces were prepared in forty human maxillary second premolars. Posts were divided into five groups of 8 each: G1 (control), no pre-treatment; G2, 10% H2O2 pre-treatment; G3, G4 and G5. After H2O2 application, Hesperidin (HES), Sodium Ascorbate (SA) or Rosmarinic acid (RA) was applied on each group respectively. In each group four posts were cemented with Duo-Link conventional resin cement and the others with self-adhesive BisCem cement. Push-out test was performed and data were analyzed using 2-way ANOVA and tukey's post-hoc test (alpha = 0.05). RESULTS: There was a statistically significant interaction between the cement type and post surface treatment on push-out bond strength of fiber posts (p < 0.001, F = 16). Also it was shown that different posts' surface treatments significantly affect the push-out bond strength of fiber posts (p = 0.001). H2O2 treated posts (G2) and control posts (G1) cemented with Duo-link showed the highest (15.96 +/- 5.07MPa) and lowest bond strengths (6.79 +/- 3.94) respectively. CONCLUSIONS: It was concluded that H2O2 surface treatment might enhance the bond strength of fiber posts cemented with conventional resin cements. The effect of antioxidants as post's surface treatment agents depends on the characteristics of resin cements used for bonding procedure.
Antioxidants* ; Ascorbic Acid ; Bicuspid ; Glass* ; Hesperidin ; Humans ; Hydrogen Peroxide* ; Reactive Oxygen Species ; Resin Cements*

A simple hollow fiber based centrifuge ultrafiltration pretreatment procedure has been developed for the analysis of active components with high polarity in Chinese traditional and herbal drugs which usually contain macromolecule impurities. The procedure combined with HPLC was applied to the determination of hesperidin in Huoxiangzhengqi water. Sample solutions were purified by our patent hollow fiber centrifuge ultrafiltration device. Under the effect of the centrifgual force, micromolecules were removed from solution samples, thus it increased the service life of the column. The accuracy and repeatability of this method have also been improved. The separation was carried out on a Promosil C18 column (4.6 mm x 150 mm, 5 microm) with methanol -0.5% acetic acid solution (35:65) as mobile phase at a flow rate of 1.0 mL x min(-1). The detector wavelength was 283 nm and the column temperature was 30 degrees C. A good linear relation was obtained in the range of 4.69 - 150 mg x L(-1) (r = 0.999 7) and the average recovery was 103.0% with RSD of 1.9%. This method is simple, rapid and accurate, and it provides a simple and cheap ultrafiltration means for the analysis of the polar components in Chinese traditional and herbal drugs.
Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Hesperidin ; analysis ; Ultrafiltration ; methods

Fifty four patients who received closed hemorrhoidectomy were randomized into two parallel groups and treated with Venitol(R)(a micronized flavonoidic fraction containing diosmin 450 mg and hesperidin 50 mg) (group 1) or placebo (group 2). Venitol(R) was administered at the dosage of three toblets b.i.d. the first four days and two tablets b.i.d following three days. Postoperative analgesia and laxative prescription as well as hospital stay were same in two groups. Though there is no difference of symptoms at D1, improvement of symptoms of complications was greater in group 1 than in group 2 at D18. The clinical severity of postoperative spot-bleeding, pain and anal discharge diminished in both groups but to a greater extent in group 1 (P<0.005). There was no side-effects in using Venitol(R). In summary, Venitol(R) is effective in reducing complications after hemorrhoidectomy.
Analgesia ; Diosmin ; Hemorrhage ; Hemorrhoidectomy* ; Hesperidin ; Humans ; Length of Stay ; Prescriptions ; Prospective Studies* ; Tablets

This study aims to evaluate the changes of flavonoid contents and antioxidants activity of Jeju native citrus fruits juice according to the harvest date. Flavonoids such as quercatagetin, narirutin, hesperidin and neohesperidin were contained most plentifully in the juice of Jigak (Citrus aur- antium) by 573.73 mg/100 mL, Sadoogam (C. pseudogulgul) by 393.99 mg /100 mL, Soyooja by 29.63 mg/100 mL and Jigak (C. aurantium) by 201.23 mg/100 mL in the late August, respectively. The highest contents of nob-iletin, sinensetin and tangeretin among polymethoxyflavones were found in the juice of Hongkyool (C. tachibana) by 7.39 mg/100 mL, 2.24 mg/100 mL, 0.63 mg/100 mL in the late August, respectively. 3,5,6,7,8,3',4'- Heptamet- hoxyflavone recorded the highest amount in Punkyool (C. tangerina) by 0.27 mg/100 mL in the late August, but the other polymethoxyflavones including 3',4',7,8-tetramethoxyflavone, 3',4'-dimethoxyflavone, 4'-methoxyflavone, 5,6,7,3',4',5'-hexamethoxyflavone, scutellarein tetramethylether were observed only trace amount in all the citrus fruits. Flavonoid contents in the citrus fruit juices were the highest during early maturation and decreased rapidly while ripening. Total polyphenol contents were the highest in the late August and decreased with ripening. However from the late December, the contents were increased again. Antioxidant activities of the fruits were evaluated as electron donating ability and were the lowest in the late September and increased with the fruit ripening. These results suggest that quercetagetin among all the flavonoids was most plentiful in Jigak and Dangyooja (C. grandis), so that the fruits could be used for industrial material of flavonoids and antioxidant agents.
Antioxidants ; Apigenin ; Chromones ; Citrus ; Disaccharides ; Electrons ; Flavanones ; Flavones ; Flavonoids ; Fruit ; Hesperidin

OBJECTIVETo develop an HPLC method for simultaneous determination of gallic acid and hesperidin in Xiaogu capsule, in order to provide a simple, rapid and accurate method for quality control of the compound preparation of traditional Chinese medicine.

METHODXiaogu capsule was extracted with methanol heating reflux method. Synergi 4 mu Hydro-RP 80A (4.6 mm x 250 mm, 5 microm) was adopted as the chromatographic column, with acetonitrile--0.04 mol x L(-1) phosphate monobasic sodium solution (20: 80) as the mobile phase. The flow rate was 1.0 mL x min(-1), the detection wavelength was 283 nm, and the column temperature was 25 degrees C.

RESULTUnder the conditions, gallic acid and hesperidin reached the baseline resolved peak, with a good linearity within the range of 21.6-216.0 mg x L(-1) (r = 0.999 93) for gallic acid, and 4.5-45.0 mg x L(-1) (r = 0.999 95) for hesperidin, respectively. Their average recoveries (n = 9) were 101.5% (RSD 3.7%) and 94.7% (RSD 2.7%), respectively. The average contents of gallic acid and hesperidin contained in Xiaogu capsule were detected to 5.10% and 0.091 1%, respectively.

CONCLUSIONThe method established in this study can determine the content of gallic acid and hesperidin contained in Xiaogu capsule in a rapid and accurate manner, which provided reference for quality evaluation of the medicine.

Capsules ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Gallic Acid ; analysis ; Hesperidin ; analysis

The present study established an RP-HPLC method for simultaneous determination of two active components in Qingfei Paidu Granules and investigated the transfer rates of neohesperidin and naringin in the preparation process to provide references for improving the quality control standard and production of Qingfei Paidu Granules.RP-HPLC was performed on a YMC Triart C_(18) column(4.6 mm×150 mm, 5 μm)with column temperature of 30 ℃, acetonitrile(A) and 0.2% phosphoric acid solution(B) as mobile phases for gradient elution at a flow rate of 1.0 mL·min~(-1) and detection wavelength of 284 nm.Good linearity was observed for naringin at 0.10-1.0 μg(R~2=0.999 9) and neohesperidin at 0.12-1.2 μg(R~2=0.999 9).The average recovery of naringin was 99.52% with an RSD of 1.2%, and that of neohesperidin was 100.8% with an RSD of 1.2%.The transfer rates of naringin and neohesperidin between medicinal materials, extracts, concentrates, and granules were measured by this method.The average transfer rate of naringin from medicinal materials to granules was 54.89%±4.38%, and that of neohesperidin was 57.63%±5.88%.The process from medicinal materials to extracts was presumedly the key link affecting the whole preparation process.The established method is simple and sensitive and can be adopted for the quality control of Qingfei Paidu Granules.Meanwhile, it can be used to investigate the transfer rate of neohesperidin and naringin in the preparation of Qingfei Paidu Granules, and further improve the quality control standard of Aurantii Fructus Immaturus in Qingfei Paidu Granules.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal ; Flavanones ; Hesperidin/analogs & derivatives*

OBJECTIVES: This study evaluated the effect of three antioxidizing agents on pull-out bond strengths of dentin treated with sodium hypochlorite. MATERIALS AND METHODS: Root canals of 75 single-rooted human teeth were prepared. Fifteen teeth were irrigated with normal saline for a negative control group, and the remaining 60 teeth (groups 2 - 5) with 2.5% NaOCl. The teeth in group 2 served as a positive control. Prior to post cementation, the root canals in groups 3 - 5 were irrigated with three antioxidizing agents including 10% rosmarinic acid (RA, Baridge essence), 10% hesperidin (HPN, Sigma), and 10% sodium ascorbate hydrogel (SA, AppliChem). Seventy-five spreaders (#55, taper .02, Produits Dentaires S.A) were coated with silica and silanized with the Rocatec system and ceramic bond. All the prepared spreaders were cemented with a self-adhesive resin cement (Bifix SE, Voco Gmbh) in the prepared canals. After storage in distilled water (24 h/37degrees C), the spreaders were pulled out in a universal testing machine at a crosshead speed of 1.0 mm/min. Pull-out strength values were analyzed by one-way ANOVA and Tukey's HSD test (alpha = 0.05). RESULTS: There were significant differences between study groups (p = 0.016). The highest pull-out strength was related to the SA group. The lowest strength was obtained in the positive control group. CONCLUSIONS: Irrigation with NaOCl during canal preparation decreased bond strength of resin cement to root dentin. Amongst the antioxidants tested, SA had superior results in reversing the diminishing effect of NaOCl irrigation on the bond strength to root dentin.
Antioxidants ; Ascorbic Acid ; Cementation ; Ceramics ; Dental Pulp Cavity ; Dentin* ; Hesperidin ; Humans ; Hydrogel ; Resin Cements* ; Silicon Dioxide ; Sodium Hypochlorite ; Tooth ; Water