Hesperidin Supplementation Research Articles

Effect of Supplementation of Hesperidin on Growth Performance, Immune Response and Antioxidant Activity in Pigs

Three experiments were conducted to investigate the effects of hesperidin supplementation on growth performance, immune function, and antioxidant activity of growing pigs (56 d old; average BW 20.4±0.6kg). In Exp. 1, 24 pigs with an initial BW of 19.53 kg were randomly allotted to three treatments, and fed for 9-wk either on a basal diet (CON), alone or with 0.01% (Hes-1), and 0.02% hesperidin (Hes2). Initial and final BW, ADG or average daily feed intake were not different among the treatments. Hes-1 or Hes-2 groups, on the other hand, had a higher (P<0.05) gain: feed ratio compared to CON group. Antioxidant activity in terms of serum superoxide dismutase activity was increased (P<0.05) in Hes-2 compared to CON group. To confirm this beneficial effect of hesperidin as an antioxidant reagent, in vitro antioxidant activities of hesperidin were ascertained vis-a-vis butylated hydroxytoluence (BHT) in Exp. 2 by using the 1, 1-diphenyl-2-picrylhydrazyl (DPPH)-radical scavenging activity. Hesperidin showed lower (P<0.05) IC50(concentration for scavenging 50% of DPPH radicals) than BHT. In Exp.3, 12 barrows (13.8±0.9 kg BW) fed 0 (CON), 0.02% (Hes-0.02) or 0.04% (Hes-0.04) of hesperidin for 4-wk were challenged with lipopolysaccharide (LPS; 50 μg/kg BW). Blood samples were obtained at 0, 3, 6, 12 and 24 h to determine immune response. There was no effect of hesperidin on levels of immuneglobulins (IgM, IgG and IgA). Taken together, administration of hesperidin has beneficial effects on feed efficiency and antioxidant activity suggesting that hesperidin can be used as a feed additive in growing pigs.

Antithyroid effects of naringin, hesperidin and rutin in l-T4 induced hyperthyroid rats: Possible mediation through 5′DI activity

BackgroundInvestigations are meager on the ameliorative role of plant based active compounds in regulating hyperthyroidism. We have now explored the possible role of three flavonoids in the regulation of L-thyroxine (l-T4)-induced hyperthyroidism in rats. This investigation attempts to reveal whether rutin, naringin and hesperidin supplementation exhibit antithyroid effects in L-T4-induced hyperthyroid rats and to work out the possible involvement of free radicals in their mode of action. MethodsEither rutin or naringin or hesperidin (50mg/kg each) was administered to L-T4-induced hyperthyroid rats for two weeks and their effects were evaluated on the alterations in levels of thyroid hormones, 5′-deiodinase I (5′DI) activity, hepatic lipid peroxidation as well as in antioxidants. Resultsl-T4 administration significantly enhanced the serum concentrations of thyroxine and triiodothyronine; the activities of hepatic 5′DI, serum lactate dehydrogenase and serum glutamate pyruvate transaminase along with an increase in content of malondialdehyde in hepatic tissues, but depleted the cellular antioxidants. However, on administration of the test flavonoids, these effects were more or less normalized. Electro paramagnetic resonance (EPR) spectra also indicated the suppression of the hydroxyl radicals (OH) in the hepatic tissues. ConclusionRutin, naringin and hesperidin have the potential to inhibit thyroid functions without hepatotoxicity and the effects are possibly mediated through their free radical scavenging action as evidenced by EPR study. From the comparative analyses of the results, rutin appeared to be the most effective one suggesting its better antithyroid and antioxidative potential over other two.

Hesperidin restores experimentally induced neurotoxicity in Wistar rats

Carbon tetrachloride (CCl4) is a highly toxic industrial solvent with pronounced systemic toxicity including brain. Neurotoxicity may be a direct result of hepatic dysfunction from CCl4 intoxication. Over the years CCl4 has been used as an excellent model for studying experimentally induced neurotoxicity in murine models. Hesperidin (HP) is a known cytoprotectant with comprehensive anti-oxidant and neuroprotective properties. The aim of the present study was to evaluate experimentally induced neurotoxicity by CCl4 and its abrogation by using antioxidant potential of HP. CCl4 caused a significant enhancement in the lipid peroxidation (LPO) levels and protein carbonyl (PC) content. HP supplementation significantly restored the LPO levels and PC content. It also replenished the altered enzymatic and non-enzymatic antioxidants in brain tissues of rats. The neurotoxicity markers were also restored to normalcy with HP treatment. It is suggested that HP, by attenuating neuronal oxidative stress, holds promise that can ameliorate CCl4-induced neurotoxicity. HP has the potential to be explored as a universal neuroprotectant in xenobiotically induced neurotoxicity mediated by oxidative stress.

Hesperidin induces apoptosis and triggers autophagic markers through inhibition of Aurora-A mediated phosphoinositide-3-kinase/Akt/mammalian target of rapamycin and glycogen synthase kinase-3 beta signalling cascades in experimental colon carcinogenesis

Abnormalities in the homeostasis mechanisms involved in cell survival and apoptosis are contributing factors for colon carcinogenesis. Interventions of these mechanisms by pharmacologically safer agents gain predominance in colon cancer prevention. We previously reported the chemopreventive efficacy of hesperidin against colon carcinogenesis. In the present study, we aimed at investigating the potential of hesperidin over the abrogated Aurora-A coupled pro-survival phosphoinositide-3-kinase (PI3K)/Akt signalling cascades. Further, the role of hesperidin over apoptosis and mammalian target of rapamycin (mTOR) mediated autophagic responses were studied. Azoxymethane (AOM) induced mouse model of colon carcinogenesis was involved in this study. Hesperidin treatment was provided either in initiation/post-initiation mode respectively. Hesperidin significantly altered AOM mediated anti-apoptotic scenario by modulating Bax/Bcl-2 ratio together with enhanced cytochrome-c release and caspase-3, 9 activations. In addition, hesperidin enhanced p53–p21 axis with concomitant decrease in cell cycle regulator. Hesperidin treatment caused significant up-regulation of tumour suppressor phosphatase and tensin homologue (PTEN) with a reduction in the expression of AOM mediated p-PI3K and p-Akt. Additionally, hesperidin administration exhibited inhibition against p-mTOR expression which in turn led to stimulation of autophagic markers Beclin-1 and LC3-II. Aurora-A an upstream regulator of PI3K/Akt pathway was significantly inhibited by hesperidin. Furthermore, hesperidin administration restored glycogen synthase kinase-3 beta (GSK-3β) activity which in turn prevented the accumulation of oncoproteins β-catenin, c-jun and c-myc. Taken together, hesperidin supplementation initiated apoptosis via targeted inhibition of constitutively activated Aurora-A mediated PI3K/Akt/GSK-3β and mTOR pathways coupled with autophagic stimulation against AOM induced colon carcinogenesis.

Effect of hesperidin dietary supplementation on hen performance, egg quality and yolk oxidative stability

1. The purpose of this study was to evaluate the effects of dietary supplementation with hesperidin (one or 3 g/kg of feed) for 31 d on the performance, egg quality and yolk oxidative stability of brown and white laying hens (26-wk old).2. Supplementation with hesperidin did not affect egg production, egg weight and egg quality traits.3. No hesperidin effect on yolk and plasma cholesterol was observed. A strain effect was found with lower total and per g yolk cholesterol of brown hens in comparison to the white ones.4. Oxidative stability of egg yolk, expressed as ng MDA/g yolk, was significantly improved in the hesperidin groups even from the first week of supplementation. At the same time, a significant improvement in the oxidative stability of egg yolk due to the incorporation of hesperidin in hens’ diet was observed after 30 and 90 d of storage at 20°C and 4°C, respectively.5. No hesperidin by strain interaction was detected for any of the traits measured.6. In conclusion, incorporation of hesperidin to laying hens’ feed did not affect productive and egg qualitative traits. On the other hand, dietary hesperidin supplementation significantly improved oxidative stability of both fresh and stored eggs. Antioxidant properties of hesperidin seem to make it a promising natural agent for improving the shelf life of eggs.

Individual and combined effects of genistein and hesperidin supplementation on meat quality in meat‐type broiler chickens

There is growing interest in improving the production and meat quality of farm animals through dietary supplementation with phytochemical (e.g. flavonoids)-rich plants and/or their extracts. This study was conducted to analyse the supplemental effects of two purified flavonoids (genistein and hesperidin) individually and in combination on the oxidative status, sensory score and quality of breast meat in meat-type broiler chickens. A significant increase (P < 0.05) in meat colour (L* score) and pH was observed for the group supplemented with 20 mg kg(-1) genistein and hesperidin. Water-holding capacity was also improved significantly (P < 0.01) for all genistein- and hesperidin-treated groups, while the sensory quality of breast meat remained unaffected. Lipid oxidation of breast meat was reduced significantly (P < 0.01) at 0 and 15 days of refrigeration in a dose-dependent manner for all supplemented groups. Meanwhile, some treated groups showed improved (P < 0.05) body weight, feed/gain ratio and hot carcass weight. Genistein and hesperidin supplementation to broilers improved meat quality in a dose-dependent fashion, with pronounced effects of combined treatment. The results indicated that purified flavonoids such as genistein and hesperidin could potentially be used as feed additives in broiler production to promote meat quality.

Hesperidin associated with continuous and interval swimming improved biochemical and oxidative biomarkers in rats.

BackgroundCitrus flavonoids, such as hesperidin, have shown therapeutic properties that improve hyperglycemia and insulin resistance, and decrease blood serum lipids and inflammation. The current investigation studied the effects of hesperidin supplementation associated with continuous and interval swimming on the biochemical parameters (glucose, cholesterol and triglycerides), and oxidative stress markers (TBARS and DPPH) in rats.MethodsThe animals (n = 60) were randomly divided in six groups: negative (C) and positive control (CH) for hesperidin supplementation, and continuous or interval swimming without (CS and IS) or with hesperidin supplementation (CSH and ISH). Hesperidin was given by gavage for four weeks (100 mg/kg body mass) before the exercise. Continuous swimming was performed for 50 min with loads from 5% to 8 % of body weight from the first to fourth week, while interval swimming training was performed for 50 min in sessions of 1 min of swimming followed by 2 min of resting, carrying loads from 10% to 15, 20 and 25% from the first to fourth week. At the end of the experiment, blood serum samples were draw to perform analysis of glucose, total cholesterol, HDL-C and triglycerides. Oxidative biomarkers were evaluated by lipid peroxidation (TBARS) and antioxidant capacity assay (DPPH) of the blood serum.ResultsThere was a continuous decline of serum glucose from C (100%) > CH (97%) > CS (94%) > CSH (91%, p < .05), IS (87%, p < .05) > ISH (80%, p < .05), showing a combined beneficial effect of hesperidin and swimming. Also, continuous or intermittent swimming with hesperidin supplementation lowered total cholesterol (-16%, p < .05), LDL-C (-50%, p < 0.05) and triglycerides (-19%, p < 0.05), and increased HDL-C (48%, p < .05). Furthermore, hesperidin enhanced the antioxidant capacity on the continuous swimming group (183%, p < .05) and lowered the lipid peroxidation on the interval swimming group (-45%, p < .05).ConclusionsHesperidin supplementation per se, or in combination with swimming exercise protocols, improved the biochemical profile and antioxidant biomarkers evidencing that the use of flavanones may enhance the health benefits promoted by exercise.

The effects of dietary hesperidin supplementation on lamb performance and meat characteristics

ABSTRACTAn experiment was conducted to examine the effects of supplementing feed with hesperidin or α‐tocopheryl acetate on lambs' growth performance, carcass and meat characteristics. Sixteen male lambs were randomly assigned to four groups. One of the groups served as control and was given a basal diet, whereas the other three groups were given the same diet further supplemented with hesperidin at 1500 mg/kg, or hesperidin at 3000 mg/kg, or α‐tocopheryl acetate at 200 mg/kg. At the end of the experiment, lambs were fasted, weighed and slaughtered. After overnight chilling, samples of Longissimus thoracis muscle were taken and were used for meat quality evaluation. No significant differences were observed in final body weight, body weight gain and organ weights among the four groups. pH, color, water‐holding capacity, shear force values and intramuscular fat concentration of Longissimus thoracis muscle were also not significantly influenced by the dietary treatments. Measurement of lipid oxidation values showed that hesperidin supplementation positively influenced meat antioxidant properties during refrigerated storage.

Hesperidin-mediated expression of Nrf2 and upregulation of antioxidant status in senescent rat heart

Oxidative stress is recognized as a key element responsible for the development of age-related pathologies. A declining endogenous defence system during senescence dictates the need for supplementation with exogenous antioxidants through diet. Hesperidin is a naturally occurring flavonone present in citrus fruits and has been shown to have many biological properties, including antioxidant activity. We investigated whether hesperidin supplementation could be valuable in protecting cardiac tissue of aged rats against age-related increase in oxidative stress, as well as the mechanism by which it can boost the antioxidant status of the cell. The activity of antioxidant enzymes, mRNA expression of Nrf2, protein levels of superoxide dismutase and catalase were measured using standard protocols. Hesperidin treatment effectively protected aged rat heart by increasing the activity of enzymic antioxidants. Hesperidin upregulated the protein levels of nuclear factor erythroid 2-related factor 2, which is responsible for maintaining the antioxidant status of the cell. Hesperidin could be useful in protecting cardiomyocytes against age-related increase in oxidative stress mediated by Nrf2 upregulation.

The effects of dietary hesperidin supplementation on broiler performance and chicken meat characteristics

Simitzis, P. E., Symeon, G. K., Charismiadou, M. A., Ayoutanti, A. G. and Deligeorgis, S. G. 2011. The effects of dietary hesperidin supplementation on broiler performance and chicken meat characteristics. Can. J. Anim. Sci. 91: 275–282. An experiment was conducted to examine the effects of supplementing broiler feed with hesperidin, a bioflavonoid that is an abundant and inexpensive by-product of citrus cultivation, on growth performance, carcass characteristics, breast meat quality characteristics and the oxidative stability of breast meat. Eighty 308-d-old Ross male broiler chickens were randomly assigned to four groups. One of the groups served as a control (C) and was given commercial basal diets, whereas the other three groups were given the same diets further supplemented with hesperidin at 1.5 g kg−1(HE1), or hesperidin at 3.0 g kg−1(HE2), or α-tocopheryl acetate at 0.2 g kg−1(VE). At 40 d of age, broilers were fasted for 12 h, weighed and slaughtered. After overnight chilling, carcasses were trimmed for breast fillets by removing skin, bones and connective tissue. The right pectoralis major muscle was used for quality parameters estimation, whereas the left pectoralis major muscle for lipid oxidation measurements. No significant differences were observed after dietary hesperidin or α-tocopheryl acetate supplementation in final body weight (kg), body weight gain (g), feed conversion rate and internal organs weight (g). Shear values (N mm−2), intramuscular fat (%) and cooking loss (%) were also not significantly influenced by the dietary treatments. Significant differences were found concerning pH24and color parameter values among the treatment groups. Measurement of lipid oxidation values showed that as hesperidin increased in the diet, malondialdehyde values decreased in tissue samples, suggesting that hesperidin particularly at 3 g kg−1exerted an antioxidant effect on chicken tissues (P&lt;0.01). However, dietary α-tocopheryl acetate supplementation at 0.2 g kg−1of feed displayed greater antioxidant activity than hesperidin at either supplementation rate (P&lt;0.01). In conclusion, hesperidin, an abundant component of citrus pulp, positively influences meat antioxidative properties without negative implications on growth performance and meat quality characteristics in poultry, thus appearing to be an important additive for both the consumer and the industry.

Hesperidin attenuates mitochondrial dysfunction during benzo(a)pyrene-induced lung carcinogenesis in mice

The present study is designed to assess the mitochondrial status during benzo(a)pyrene (B(a)P)-induced lung carcinogenesis in Swiss albino mice and to reveal the modulatory effect of hesperidin over it. B(a)P (50 mg/kg body weight)-induced mitochondrial abnormalities was evident from alterations in mitochondrial lipid peroxides, antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione, vitamin E, and vitamin C), major tricarboxylic acid (TCA) cycle enzyme activities (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase), electron transport chain (ETC) complexes activities and ATP levels. Ultrastructural changes in lung mitochondria were also in accord with the above aberrations. Hesperidin (25 mg/kg body weight) supplementation effectively counteracted all the above changes and restored cellular normalcy, indicating its protective role during B(a)P-induced lung cancer.

Antioxidant and anticancer efficacy of hesperidin in benzo(a)pyrene induced lung carcinogenesis in mice

Chemoprevention is regarded as one of the most promising and realistic approaches in the prevention of cancer. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on lung cancer. Hesperidin is one such naturally occurring flavonoid widely found in citrus fruits. The aim of the present study is to divulge the chemopreventive nature of hesperidin during benzo(a)pyrene (B(a)P) induced lung cancer in Swiss albino mice. Administration of B(a)P (50 mg/kg body weight) to mice resulted in increased lipid peroxides (LPO), lung specific tumor marker carcinoembryonic antigen (CEA) and serum marker enzymes aryl hydrocarbon hydroxylase (AHH), gamma glutamyl transpeptidase (GGT), 5'nucleotidase (5'ND) and lactate dehydrogenase (LDH) with concomitant decrease in the levels of tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin E and vitamin C. Hesperidin supplementation (25 mg/kg body weight) significantly attenuated these alterations thereby showing potent anticancer effect in lung cancer. Further the antiproliferative effect of hesperidin was confirmed by histopathological analysis and proliferating cell nuclear antigen (PCNA) immunostaining. Overall, these findings substantiate the chemopreventive potential of hesperidin against chemically induced lung cancer in mice.

Effect of Hesperidin Supplementation on Lipid and Antioxidant Metabolism in Ethanol-fed Rats

This study examined the effect of hesperidin supplementation with an ethanol diet on lipid and antioxidant metabolism in rats. Male Sprague-Dawley rats were divided into two groups (n=10), and were assigned to one of two dietary categories: E?, ethanol diet (50 g/L) for 8 wks; E?H₄, ethanol diet for the first 4 wks and hesperidin (0.02%, w/w) supplemented ethanol diet for the last 4 wks. The plasma and hepatic lipids, hepatic cholesterol regulating enzyme activity, hepatic antioxidant enzyme activity and lipid peroxidation were determined. Supplementation with hesperidin for the last 4 wks during the 8 wks period of the ethanol diet, significantly increased the ADH activity. In conjunction with the chronic administration of ethanol, hesperidin supplementation resulted in a significant decrease in the hepatic cholesterol and triglyceride concentrations compared to the E? group. The hepatic HMG-CoA reductase and ACAT activities were significantly lower in the hesperidin-supplemented group. When comparing hepatic antioxidant enzyme activities, SOD, GSH-Px, and G6PD activities and GSH level were significantly higher in the E?H₄ group than in the E? group. Plasma TBARS levels were significantly lower in rats fed ethanol with hesperidin compared to the rats fed only ethanol; however, the hepatic TBARS levels were not significantly different between the groups. Accordingly, the additional hesperidin supplement with an ethanol diet might be effective for improving the hepatic lipid metabolism and antioxidant defense system.

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.