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At least 19 recordsLinked to original sources
PubMed2005

HPLC separation of hesperidin and the C-2 epimer in commercial hesperidin samples and herbal medicines.

Hesperidin (2S-form), the flavanone 7-O-glycoside, is the main constituent of some Citrus species. The peels of two Citrus species are used as a crude drug, Aurantii nobilis pericarpium, in the Japanese Pharmacopoeia and as components in Kampo formulae. Thus, HPLC analysis of hesperidin as a marker compound is needed for quality control of medicines. Hesperidin was separated from the corresponding C-2 epimer by normal-phase HPLC using a chiral column. Moreover, narirutin and neohesperidin were also separated from the corresponding C-2 epimer. The analyses of commercial hesperidin samples revealed that they contained the C-2 epimer and that the relative ratio of hesperidin to the epimer ranged from 92:8 to 59:41. The HPLC application to Citrus extracts suggested that naturally occurring hesperidin in Citrus has the 2S configuration; however, the dry extracts of rikkunshito and chotosan, which are Kampo formulations containing Aurantii nobilis pericarpium, were found to contain a considerable amount of the (2R)-epimer. These data suggest that the decoction process of the formulae partly converts hesperidin to the epimer. Because diastereomers differ from each other in physicochemical and biological activities, HPLC to separate hesperidin from the C-2 epimer should be introduced into the letter of approval for herbal medicines.

Chromatography, High Pressure Liquid↗
PubMed2002

Effects of long-term administration of hesperidin and glucosyl hesperidin to spontaneously hypertensive rats.

Hesperidin (HES) is a flavonoid contained in citrus fruit peel. We investigated the effects of long-term administration of HES and its newly developed water soluble analogue, glucosyl hesperidin (GHES), to spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Animals were fed with diets containing HES or GHES (30 mg/d/kg body weight) for 25 wk. While the daily food intake and the body weight of administered rats were not different from those of the non-administered control rats in both SHR and WKY through the experimental period, the blood pressure and heart rate of SHR administered HES or GHES for longer than 15 wk decreased as compared to the control group. The blood pressure and heart rate of WKY were not changed by the long-term administration of HES or GHES. These results suggest that HES and GHES have anti-hypertensive effects on hypertensive animals.

Animals↗
PubMed2001

Interactive effect of hesperidin and vitamin E supplements on cholesterol metabolism in high cholesterol-fed rats.

Certain bioflavonoids are potent antioxidants and have pharmacologic effects similar to those of vitamin E. Accordingly, the interactive effect of hesperidin and vitamin E was studied with respect to cholesterol metabolism and the antioxidant status. Hesperidin supplement (0.1%, wt/wt) with comparable levels of vitamin E was provided with a high-cholesterol (1%, wt/wt) diet to rats for 5 weeks. The amount of vitamin E included in the hesperidin-free and hesperidin diets was either a low (low-E) or a normal (normal-E) level. The hesperidin supplement and different levels of dietary vitamin E did not significantly alter the concentrations of plasma triglycerides. However, the inclusion of hesperidin significantly lowered the concentration of plasma cholesterol in both the low-vitamin E group and the normal-vitamin E group compared to the hesperidin-free groups (p < 0.05). The hepatic triglyceride content was significantly lowered by the hesperidin supplement, as opposed to the plasma triglyceride content, regardless of the vitamin E level in the diet. The hepatic HMG-CoA reductase activity was significantly lowered by the hesperidin supplement with both the low-vitamin E and the normal-vitamin E compared to the hesperidin-free groups (p < 0.05). The hepatic HMG-CoA reductase activity was also significantly lowered with an increase in the dietary vitamin E within the hesperidin and hesperidin-free groups. The excretion of fecal neutral sterol and acidic sterols tended to be lower with the hesperidin supplement. Neither dietary hesperidin nor vitamin E significantly changed the hepatic antioxidant enzyme activity. This data indicates that hesperidin lowers the concentration of plasma cholesterol and the hepatic triglyceride content regardless of the dietary vitamin E level. However, the concentration of plasma cholesterol in the hesperidin-free groups was dependent on the dietary vitamin E level. This information may contribute to understanding the interactive effect of hesperidin and vitamin E on cholesterol biosynthesis in high cholesterol-fed rats.

Animals↗
PubMed2006

Bioavailability of glucosyl hesperidin in rats.

Glucosyl hesperidin (G-hesperidin) is a water-soluble derivative of hesperidin. We compared the absorption and metabolism of G-hesperidin with those of hesperidin in rats. After oral administration of G-hesperidin or hesperidin to rats, hesperetin was detected in sera hydrolyzed with beta-glucuronidase, but it was not detectable in unhydrolyzed sera. Serum hesperetin was found more rapidly in rats administered G-hesperidin than in those administered hesperidin. The area under the concentration-time curve for hesperetin in the sera of rats administered G-hesperidin was approximately 3.7-fold greater than that of rats administered hesperidin. In the urine of both administration groups, hesperetin and its glucuronide were found. Urinary excretion of metabolites was higher in rats administered G-hesperidin than in those administered hesperidin. These results indicate that G-hesperidin presents the same metabolic profile as hesperidin. Moreover, it was concluded that G-hesperidin is absorbed more rapidly and efficiently than hesperidin, because of its high water solubility.

Administration, Oral↗
PubMed2006

Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: a randomized, double-blind, crossover trial.

Hesperidin is the predominant polyphenol consumed from citrus fruits and juices. However, hesperidin is proposed to have limited bioavailability due to the rutinoside moiety attached to the flavonoid. The aim of this study was to demonstrate in human subjects that the removal of the rhamnose group to yield the corresponding flavonoid glucoside (i.e., hesperetin-7-glucoside) will improve the bioavailability of the aglycone hesperetin. Healthy volunteers (n=16) completed the double-blind, randomized, crossover study. Subjects randomly consumed hesperetin equivalents supplied as orange juice with natural hesperidin ("low dose"), orange juice treated with hesperidinase enzyme to yield hesperetin-7-glucoside, and orange juice fortified to obtain 3 times more hesperidin than naturally present ("high dose"). The area under the curve (AUC) for total plasma hesperetin of subjects consuming hesperetin-7-glucoside juice was 2-fold higher than that of subjects consuming the "low" dose hesperidin juice [3.45+/-1.27 vs. 1.16+/-0.52 mmol/(L.h), respectively, P>0.0001]. The AUC for hesperetin after consuming the hesperetin-7-glucoside juice was improved to the level of the "high" dose hesperidin juice [4.16+/-1.50 mmol/(L.h)]. The peak plasma concentrations (C(max)) of hesperetin were 4-fold higher (2.60+/-1.07 mmol/L, P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with those consuming "low" dose hesperidin juice (0.48 +/- 0.27 mmol/L), and 1.5-fold higher than those consuming "high" dose hesperidin juice (1.05+/-0.25 mmol/L). The corresponding T(max) was much faster (0.6+/-0.1 h, P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with "low" dose (7.0+/-3.0 h) and "high" dose (7.4+/-2.0 h) hesperidin juices. The results of this study demonstrated that the bioavailability of hesperidin was modulated by enzymatic conversion to hesperetin-7-glucoside, thus changing the absorption site from the colon to the small intestine. This may affect future interventions concerning the health benefits of citrus flavonoids.

Adult↗
PubMed2006

Suppression of apolipoprotein B secretion from HepG2 cells by glucosyl hesperidin.

Our previous study has shown that a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), preferentially lowers serum triglyceride (TG) level in hypertriglyceridemic subjects through the improvement of very low-density lipoprotein (VLDL) metabolic abnormality. G-Hesperidin has also been found to decrease an elevated serum apolipoprotein B (apo B) level in the hypertriglyceridemic subjects, suggesting a possibility that this compound suppresses excess VLDL secretion in the liver. In the present study, to gain a better understanding of possible mechanisms by which G-hesperidin lowers serum TG, we examined whether this derivative affects apo B secretion from HepG2 human hepatoma cells, a model of hepatic VLDL secretion. As a result, G-hesperidin significantly reduced apo B secretion from the oleate-stimulated HepG2 cells. Furthermore, G-hesperidin significantly suppressed apo B secretion only in the oleate-stimulated cells and failed to act on the cells incubated without oleate. In the oleate-stimulated cells, G-hesperidin significantly decreased cellular cholesteryl ester (CE), although it had no effect on cellular TG or free cholesterol amounts. Moreover, the oleate-stimulated cells had a decrease in cellular apo B amounts by G-hesperidin exposure. These findings indicate that G-hesperidin down-regulates the assembly of apo B-containing lipoproteins via the reduction of CE synthesis augmented with oleate and results in suppressing excess apo B secretion from the cells. This effect is speculated to be associated with the improvement of VLDL metabolic abnormality in hypertriglyceridemic subjects and considered as a mechanism of lowering serum TG.

Analysis of Variance↗
PubMed1997

Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats by flavonoids diosmin and hesperidin, each alone and in combination.

The modifying effects of the two flavonoids diosmin and hesperidin given during the initiation and postinitiation phases of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. The compounds were tested alone and in combination. At 6 weeks of age, animals were divided into experimental and control groups and fed diets containing 1000 ppm diosmin and 1000 ppm hesperidin and a diet containing both compounds (900 ppm diosmin and 100 ppm hesperidin). At 7 weeks of age, all animals except those treated with each test chemical alone and control groups were given 4-NQO (20 ppm) in the drinking water for 8 weeks to induce oral cancer. Starting 7 days before the 4-NQO exposure, groups of animals were fed the diets containing test chemicals for 10 weeks and then switched to the basal diet. Starting 1 week after the cessation of 4-NQO exposure, the groups given 4-NQO and a basal diet were switched to the diets containing diosmin, hesperidin, or diosmin combined with hesperidin and maintained on these diets for 22 weeks. The other groups consisted of rats given diosmin (1000 ppm), hesperidin (1000 ppm), and the combination regimen of these two compounds (900 ppm diosmin with 100 ppm hesperidin) alone, and untreated rats. All animals were necropsied at the termination of the study (week 32). The incidences of tongue lesions (neoplasms and preneoplasms), polyamine levels in the tongue tissue, and cell proliferation activity estimated by a 5-bromodeoxyuridine-labeling index and by morphometric analysis of silver-stained nucleolar organizer regions protein were compared among the groups. Feeding of both compounds singly or in combination during the initiation phase caused a significant reduction in the frequency of tongue carcinoma [diosmin, 68% reduction (P < 0.01); hesperidin, 75% reduction (P < 0.005); and the combination regimen, 69% (P < 0.05)]. When fed the test compounds singly or the combination regimen after 4-NQO exposure, the frequency of tongue cancer was also decreased [diosmin, 77% reduction (P < 0.005); hesperidin, 62% reduction (P < 0.05); and the combination regimen, 77% (P < 0.005)]. The incidences of oral preneoplasia (hyperplasia and dysplasia) in these groups were also decreased when compared with carcinogen controls (P < 0.05-P < 0.001). There were no pathological alterations in rats treated with test compounds or the combined regimen alone or those in an untreated control group. Dietary administration of these compounds significantly decreased the expression of cell proliferation biomarkers (5-bromodeoxyuridine-labeling index and silver-stained nucleolar organizer regions protein number) of the nonlesional tongue squamous epithelium (P < 0.05). Also, polyamine concentrations in the oral mucosa were lowered in rats given the carcinogen and test compounds, alone and in combination, compared with those of rats given 4-NQO alone (P < 0.05). These findings suggest that supplementation with the flavonoids diosmin and hesperidin, individually and in combination, is effective in inhibiting the development of oral neoplasms induced by 4-NQO, and such inhibition might be related to suppression of increased cell proliferation caused by 4-NQO in the oral mucosa.

4-Nitroquinoline-1-oxide↗
PubMed2004

Determination of extracellular hesperidin in blood and bile of anaesthetized rats by microdialysis with high-performance liquid chromatography: a pharmacokinetic application.

A method coupled with microdialysis technique and liquid chromatography was applied in the continuous and concurrent in vivo monitoring of extracellular hesperidin in the blood and bile of anaesthetized rats. Hesperidin was intravenously administered via the femoral vein. Sampling was achieved using two microdialysis probes, which were implanted into the jugular vein and into the bile duct. Dialysates of blood and bile were both directly injected onto the liquid chromatographic system, so no further clean-up procedures were required. Separation was performed using a reversed phase ODS-2 microbore column 150 mm x 1 mm i.d., particle size 5 microm with mobile phase of acetonitrile-0.1M ammonium acetate (30:70, v/v) at flow-rate of 0.05 ml/min. The UV detection for hesperidin was set at a wavelength of 283 nm. This method was used to determine the pharmacokinetics of hesperidin and its interaction in the presence of cyclosporin A, which is a P-glycoprotein modulator. The results indicate that the curve of area under the concentration versus time (AUC) for hesperidin in bile was significantly greater than that for hesperidin in blood at the dose of 30 mg/kg. The blood-to-bile distribution ratio (k = AUC(bile)/AUC(blood)) was 8.9 +/- 2.5 for hesperidin at 30 mg/kg. Following cyclosporin A treatment, the distribution ratio was reduced to 3.2 +/- 0.6. In conclusion, hesperidin goes through hepatobiliary elimination against the concentration gradient from blood to bile, and this hepatobiliary excretion of hesperidin may be regulated by the P-glycoprotein.

Anesthesia↗
PubMed1997

Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin.

The modulating effects of dietary feeding of two flavonoids, diosmin and hesperidin, both alone and in combination, during the initiation and post-initiation phases on colon carcinogenesis initiated with azoxymethane (AOM), were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks to induced colon neoplasms. Rats were fed the diets containing diosmin (1000 ppm), hesperidin (1000 ppm) or diosmin (900 ppm) + hesperidin (100 ppm) for 5 weeks (initiation treatment) or 28 weeks (post-initiation treatment). The others contained the groups of rats treated with diosmin, hesperidin alone or in combination, and untreated. At the end of the study (32 weeks), the incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the large intestine of rats initiated with AOM together with, or followed by, a diet containing diosmin or hesperidin were significantly smaller than those of rats given AOM alone (P <0.001). The combination regimen during the initiation and post-initiation stages also inhibited the development of colonic neoplasms, but the tumor data did not indicate any beneficial effect of diosmin and hesperidin administered together as compared with when these agents were given individually. In addition, feeding of diosmin and hesperidin, both alone and in combination, significantly inhibited the development of aberrant crypt foci. As for cell proliferation biomarkers, dietary exposure of diosmin and hesperidin significantly decreased the 5'-bromodeoxyuridine-labeling index and argyrophilic nuclear organizer region's number in crypt cells, colonic mucosal ornithine decarboxylase activity, and polyamine levels in the blood. These results indicate that diosmin and hesperidin, both alone and in combination, act as a chemopreventive agent against colon carcinogenesis, and such effects may be partly due to suppression of cell proliferation in the colonic crypts, although precise mechanisms should be clarified.

Animals↗
PubMedDate not supplied

Kinetics of radical-scavenging activity of hesperetin and hesperidin and their inhibitory activity on COX-2 expression.

The radical-scavenging activities of the flavanones hesperetin and hesperidin were investigated by differential scanning calorimetry (DSC) monitoring of the polymerization of methyl methacrylate initiated by 2,2'-azobisisobutyronitrile (AIBN, an R* radical) or benzoylperoxide (BPO, a PhCOO* radical) at 70 degrees C under nearly anaerobic conditions. Their stoichiometric factor (number of free radicals trapped by one mole of antioxidant moiety (n)) and the ratio of the rate constant of inhibition to that of propagation (k(inh)/k(p)) were determined and compared with that for trolox The n value declined in the order trolox (2.0) > hesperetin (0.8) > hesperidin (0.2) in the AIBN system, whereas it declined in the order hesperetin (0.9) > trolox (0.1) > hesperidin (0.0) in the BPO system. The k(inh)/k(p) value declined in the order hesperidin (195) > hesperetin (33) > trolox (12) in the AIBN system, whereas it declined in the order hesperidin (362) > trolox (127) > hesperetin (18) in the BPO system. The n value of about 1 for hesperetin with a relatively small k(inh)/k(p) value suggests the formation of dimers, as a result of the coupling reaction of phenolic monomers. In contrast, n values << 1 for hesperidin and trolox in the BPO system resulted in very high values for k(inh)/k(p). Hesperidin was also much more able to suppress the growth of methyl methacrylate radicals, although its n value was small, suggesting that this compound may also suppress polyunsaturated fatty acid radicals. In the concentration range 250-500 microM, hesperetin and hesperidin showed potent inhibition of LPS-induced expression of the COX-2 gene in RAW 264.7 cells, suggesting the anti-inflammatory activity of these compounds. The ability of hesperetin and hesperidin to suppress COX-2 gene expression may be a consequence of their antioxidant activity.

Animals↗
PubMed2004

Effects of glucosyl hesperidin on serum lipids in hyperlipidemic subjects: preferential reduction in elevated serum triglyceride level.

Although hesperidin lowers serum total cholesterol (TC) or triglyceride (TG) in animal models, its effect in humans remains unclear. Using a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), as a hesperidin source, we examined the efficacy on hyperlipidemic subjects. G-Hesperidin was administered to the subjects at 100 or 500 mg/d for 6 wk. The percentage of subjects who had a change in serum cholesterol levels was less than 20%. However, 45-55% of the total subjects showed a reduction in serum TG level. The subjects were classified into normal (TC<230mg/dL, TG<150mg/dL), high-TC (TC>230 mg/dL, TG<150 mg/dL) and high-TG (TG>150 mg/dL) types. While serum cholesterol levels scarcely changed in any phenotype, TG level was significantly reduced by administration in the high-TG type. In this phenotype, serum apolipoprotein (apo) C-II and E levels decreased by the administration, but non-apo B. G-Hesperidin also raised low-density lipoprotein (LDL)-cholesterol/apo B in the high-TG type. These results indicate that G-hesperidin preferentially lowers serum TG in hypertriglyceridemic subjects and that this effect is possibly caused by the facilitation of catabolism of TG-rich lipoproteins and may contribute to the reduction of small dense LDL.

Adult↗
PubMed2005

Glucosyl hesperidin lowers serum triglyceride level in hypertriglyceridemic subjects through the improvement of very low-density lipoprotein metabolic abnormality.

To examine the serum triglyceride (TG)-lowering effect of a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), and its mechanisms, we carried out a G-hesperidin administration test in hypertriglyceridemic subjects. G-Hesperidin was administered to the subjects at 500 mg/d for 24 wk. In this study, the subjects were classified into high-TG type (TG > 150 mg/dL), borderline-TG type (TG 110-150 mg/dL) and normal-TG type (TG < 110 mg/dL) on the basis of their initial serum TG values. Among these phenotypes, serum TG level significantly decreased in the high-TG type during the G-hesperidin administration period. It was also observed that elevated values of serum remnant-like particle cholesterol (RLP-C), apolipoprotein (apo) B, apo C-II, apo C-III and apo E occurred in the high-TG type and that these serum levels were significantly reduced by G-hesperidin administration. Moreover, polyacrylamide gel electrophoresis analysis of serum lipoproteins revealed that the very low-density lipoprotein (VLDL)/low-density lipoprotein (LDL) ratio and LDL migration index of the high-TG type were remarkably higher than those of the other phenotypes but that their high values were significantly reduced by the administration. These results indicate that G-hesperidin preferentially lowers serum TG in hypertriglyceridemic subjects and that this effect is possibly caused by the improvement of VLDL metabolic abnormality, leading to the reduction of small dense LDL.

Adult↗
PubMed2006

Determination of hesperidin in Pericarpium Citri Reticulatae by semi-micro HPLC with electrochemical detection.

Determination of hesperidin contents in Pericarpium Citri Reticulatae was performed by a simple extraction with methanol and semi-micro high-performance liquid chromatography with electrochemical detection (muHPLC-ECD). Chromatography was performed using a microbore octadecylsilica (ODS) column, methanol-water-phosphoric acid (40:60:0.5, v/v/v), as a mobile phase and applied potential at +0.9 V versus Ag/AgCl. Peak heights were found linearly related to the concentrations of hesperidin injected 9.16 ng/ml to 3.06 microg/ml (r>0.999). The detection limit (S/N=3) was 3.06 ng/ml (15.3 pg). Hesperidin of 305 ng/ml was detected with a relative standard deviation (R.S.D.) of 0.79% (n=5). Hesperidin in Pericarpium Citri Reticulatae was extracted with methanol, diluted with the mobile phase, and injected into the muHPLC-ECD for determination. The hesperidin content of Pericarpium Citri Reticulatae from four different districts in China were determined with R.S.D. of 3.59%, 2.29%, 2.36%, and 2.32% (n=5), respectively. Recoveries of hesperidin from the four Pericarpium Citri Reticulatae sources were 100.3%, 99.83%, 100.7%, and 100.6%, respectively. This method is useful for the determination of hesperidin in Pericarpium Citri Reticulatae, and especially so for instances when samples are sparse.

China↗
PubMed2005

Antioxidant activity of the flavonoid hesperidin in chemical and biological systems.

The antioxidant hesperidin, a major flavonoid in sweet orange and lemon, was evaluated using chemical and biological systems. The chemical assay evaluates the hesperidin capacity to sequester 1,1-diphenyl-2-picrylhydrazyl (DPPH*). Biological studies were done using the eukaryotic cells of superoxide-dismutase proficient and deficient strains of Saccharomyces cerevisiae treated with hesperidin and the stressing agents hydrogen peroxide or paraquat (methylviologen; 1,1'-dimethyl-4,4'-bipyridinium dichloride). Hesperidin was able to reduce significantly the level of the free radical DPPH* with similar efficacy of trolox (positive control). When the yeast cells were exposed to the flavonoid hesperidin before the stressing agents, there was a significant increase in the survival of all strains. Paraquat induced higher catalase and superoxide dismutase than did hydrogen peroxide, which only increased catalase activity. Previous addition of hesperidin to these treatments was able to reduce significantly both enzymatic levels. These observations clearly demonstrate that hesperidin provides strong cellular antioxidant protection against the damaging effects induced by paraquat and peroxide hydrogen.

Antioxidants↗
PubMed1997

Modulation of N-methyl-N-amylnitrosamine-induced rat oesophageal tumourigenesis by dietary feeding of diosmin and hesperidin, both alone and in combination.

The modifying effects of flavonoids diosmin and hesperidin during the initiation and post-initiation phases of oesophageal carcinogenesis initiated with N-methyl-N-amylnitrosamine (MNAN) were investigated in male Wistar rats. At 7 weeks of age, all animals except those treated each test chemical alone and control groups were given weekly intraperitoneal injections of MNAN (12.5 mg/kg body weight/injection) for 12 weeks to induce oesophageal neoplasms. For examining the modifying effects of 'initiation' treatment of test compounds, groups of animals were fed the diets containing 1000 ppm diosmin and 1000 ppm hesperidin, and the diet containing both compounds (900 ppm diosmin and 100 ppm hesperidin) for 13 weeks, starting 7 days before the MNAN dosing and then switched to the basal diet. For examining the modifying effects of 'post-initiation' treatment of these compounds, the groups given MNAN and a basal diet were switched to the experimental diets containing diosmin, hesperidin or diosmin combined with hesperidin at 1 week after the stop of MNAN injection, and maintained on these diets for 7 weeks. The other groups consisted of rats given test compounds alone or untreated rats. All animals were necropsied at the termination of the study (week 20) to determine the incidences of oesophageal neoplasms and preneoplasms, blood polyamine levels, and cell proliferation activity estimated by 5-bromodeoxyuridine (BrdU)-labelling index and by morphometric analysis of silver-stained nucleolar organizer regions' protein (AgNORs). A number of oesophageal neoplasms developed in rats treated with MNAN alone (75% and 100% incidences of carcinoma and papilloma, respectively). 'Initiation' feeding of diosmin significantly decreased the incidence of squamous cell carcinoma (P < 0.05). Also, 'initiation feeding' of both compounds singly or in combination caused a significant reduction in the multiplicities of oesophageal carcinoma and papilloma (diosmin, 78 and 58% reduction; hesperidin, 70 and 50% reduction; and the combination regimen, 70 and 30% reduction, P < 0.005). 'Post-initiation' feeding slightly decreased the multiplicities of these oesophageal neoplasms. Also, these dietary regimens reduced the multiplicities of preneoplastic lesions (hyperplasia and severe dysplasia; P < 0.05). There were no pathological alterations in rats treated with both compounds alone or the combined regimen alone or those in an untreated control group. Similarly, feeding of these compounds significantly decreased the expression of cell proliferation biomarkers (BrdU-labelling index and AgNORs number) of the non-lesional oesophageal epithelium (P < 0.05). Blood polyamine concentrations were also lowered in rats given the carcinogen and test compounds, both alone and in combination, when compared with those of rats given MNAN alone (P < 0.05). These findings suggest that diosmin and hesperidin supplementation, individually or in combination, is effective in inhibiting the development of oesophageal cancer induced by MNAN when given during the initiation phase, and such inhibition might be related to suppression of increased cell proliferation caused by MNAN in the oesophageal mucosa.

Administration, Oral↗
PubMed2003

Hesperidin, a citrus flavonoid, inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice.

The purpose of this study was to examine whether hesperidin inhibits bone loss in ovariectomized mice (OVX), an animal model of postmenopausal osteoporosis. Forty 8-wk-old female ddY mice were assigned to five groups: a sham-operated group fed the control diet (AIN-93G), an OVX group fed the control diet, an OVX+HesA group fed the control diet containing 0.5 g/100 g hesperidin, and an OVX+HesB group fed the control diet containing 0.7 g/100 g alpha-glucosylhesperidin and an OVX+17beta-estradiol (E(2)) group fed the control diet and administered 0.03 micro g E(2)/d with a mini-osmotic pump. After 4 wk, the mice were killed and blood, femoral, uterine and liver were sampled immediately. Hesperidin administration did not affect the uterine weight. In OVX mice, the bone mineral density of the femur was lower than in the sham group (P < 0.05) and this bone loss was significantly prevented by dietary hesperidin or alpha-glucosylhesperidin. The Ca, P and Zn concentrations in the femur were significantly higher in the hesperidin-fed and E(2) groups than in the OVX group. Histomorphometric analyses showed that the trabecular bone volume and trabecular thickness in the femoral distal metaphysis were markedly decreased (P < 0.05) by OVX, and alpha-glucosylhesperidin significantly prevented this bone loss. Furthermore, hesperidin decreased the osteoclast number of the femoral metaphysis in OVX mice, as did E(2). Serum and hepatic lipids were lower in mice that consumed the hesperidin-containing diets (P < 0.05) than in the OVX group fed the control diet. These results suggest a possible role for citrus flavonoids in the prevention of lifestyle-related diseases because of their beneficial effects on bone and lipids.

Animals↗
PubMed1994

Pharmacological evaluation of the anti-inflammatory activity of a citrus bioflavonoid, hesperidin, and the isoflavonoids, duartin and claussequinone, in rats and mice.

Pretreatment of rats with hesperidin (50 and 100 mg kg-1, s.c.) reduced the paw oedema induced by carrageenan by 47 and 63%, respectively, within 5 h. The effect was equivalent to that produced by indomethacin (10 mg kg-1, p.o.), although unrelated to the administered dose, particularly at high doses. At 100 mg kg-1 hesperidin decreased the rat paw oedema induced by dextran by 33%, without influencing the histamine-induced paw oedema. Hesperidin also inhibited pleurisy induced by carrageenan, reducing the volume of exudate and the number of migrating leucocytes by 48 and 34%, respectively, of control values. Equal doses of duartin and claussequinone were ineffective in all the above tests. Pretreatment of mice with hesperidin (100 mg kg-1, s.c.) reduced acetic acid-induced abdominal constriction by 50%, but did not affect the tail flick response. Hyperthermia induced by yeast in rats was slightly reduced by hesperidin. No lesions of the gastric mucosae were detected in rats pretreated with hesperidin. The results indicate that hesperidin obtained from citrus cultures may present a potential therapeutical use as a mild anti-inflammatory agent, being also useful as a precursor of new flavonoids endowed with such activity.

Analgesia↗
PubMed1999

Anti-inflammatory activity of diosmin and hesperidin in rat colitis induced by TNBS.

The intestinal anti-inflammatory activity of two flavonoids, hesperidin and diosmin, was evaluated in the acute stage of the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. The results obtained showed that pretreatment with diosmin (10 mg/kg) or hesperidin (10 and 25 mg/kg) reduced colonic damage compared to TNBS control rats. This effect was confirmed biochemically by a reduction in colonic myeloperoxidase activity compared to non-treated colitic animals. Colonic glutathione levels in colitic animals were significantly increased after hesperidin or diosmin treatment. Diosmin decreased colonic MDA production and inhibited LTB4 synthesis, whereas hesperidin failed to do so. Conversely, only hesperidin improved colonic fluid absorption, which was impaired in colitic animals. In conclusion, both diosmin and hesperidin were able to prevent colonic inflammation, acting via a mechanism in which protection against oxidative insult may play a role.

Animals↗