Disease relevance of hesperidin

• 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)] [1].
• 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 [2].
• The current results suggest that hesperidin and naringin both play important roles in preventing the progression of hyperglycemia, partly by increasing hepatic glycolysis and glycogen concentration and/or by lowering hepatic gluconeogenesis [3].
• The purpose of this study was to examine whether hesperidin inhibits bone loss in ovariectomized mice (OVX), an animal model of postmenopausal osteoporosis [4].
• Daflon 500 mg, is a micronized purified flavonoid fraction, containing 90% w/w diosmin and 10% w/w of flavonoids expressed as hesperidin, used clinically in the treatment of chronic venous insufficiency and hemorrhoidal disease [5].

High impact information on hesperidin

• 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 [1].
• At 6 weeks of age, rats were divided into experimental and control groups and fed the diet containing beta-carotene, hesperidin, or curcumin at a dose of 0.5 g/kg diet (500 ppm) [6].
• Cumulative urinary recovery indicated low bioavailability ( < 25%) of naringin and hesperidin [7].
• Micronised purified flavonoid fraction (MPFF) [Daflon 500 mg], an oral phlebotropic drug consisting of 90% micronised diosmin and 10% flavonoids expressed as hesperidin, improves venous tone and lymphatic drainage, and reduces capillary hyperpermeability by protecting the microcirculation from inflammatory processes [8].
• In the present study, we investigated the modifying effects of a commercial Satsuma mandarin (Citrus unshiu Marc.) juice (MJ) and those of MJ2 and MJ5, which were prepared from MJ and are richer in beta-cryptoxanthin and hesperidin than MJ, on the occurrence of colonic tumors induced by AOM in male F344 rats [9].

Chemical compound and disease context of hesperidin

• Consequently, the current results suggest that hesperidin and naringin are beneficial for improving hyperlipidemia and hyperglycemia in type-2 diabetic animals by partly regulating the fatty acid and cholesterol metabolism and affecting the gene expression of glucose-regulating enzymes [10].
• 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 [11].
• Subchronic toxicity study of methyl hesperidin in mice [12].
• In conclusion, hesperidin and lipoic acid provided protective effects against As(III)-induced acute toxicity in the liver and kidneys of mice [13].
• The effect of a clinically used purified micronized flavonoid fraction (90% diosmin and 10% hesperidin) on leukocyte-endothelial cell interaction during ischemia-reperfusion injury was studied in the microcirculation of unanesthetized hamsters fitted with a skin fold window chamber [14].

Biological context of hesperidin

• 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 [2].
• 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)] [15].
• Two other flavonoids tested, rutin and hesperidin, were ineffective in inhibiting cell growth [16].
• 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 [4].
• Crude flavonoids, eriocitrin, and hesperidin suppressed the oxidative stress in the diabetic rats [17].

Anatomical context of hesperidin

• 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 [18].
• Furthermore, hesperidin decreased the osteoclast number of the femoral metaphysis in OVX mice, as did E(2) [4].
• 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 [15].
• In the present study, the two pairs of flavonoids of hesperetin (HT) and hesperidin (HD; HT-7-rutinose), and naringenin (NE) and naringin (NE-7-rutinose), were used to study their apoptosis-inducing activities in HL-60 cells [19].
• Myocrisin, fenoprofen, phosphorulated hesperidin and PS53 (a hydroquinone-sulfonic acid-formaldehyde polymer) inhibited fertilization when incubated with capacitated spermatozoa before the treated spermatozoa were mixed with intact oocytes but not when the inhibitor-treated, capacitated spermatozoa were added to oocytes free of follicle cells [20].

Associations of hesperidin with other chemical compounds

• We have reported protective effects of dietary administration of a powder "CHRP" containing high amounts of beta-cryptoxanthin and hesperidin prepared from a Satsuma mandarin (Citrus unshiu Marc.) juice on azoxymethane (AOM)-induced rat aberrant crypt foci through suppression of crypt cell proliferation and/or induction of detoxifying enzymes [9].
• We conclude that berberine, curcumin and hesperidin can increase mucin release by directly acting on airway mucin-secreting cells and suggest that these agents be further studied for possible use as mild expectorants during the treatment of chronic airway diseases [21].
• The oxidative stress of eriocitrin (eriodictyol 7-O-beta-rutinoside) and hesperidin (hesperetin 7-O-beta-rutinoside) on streptozotocin-induced diabetic rats was investigated [17].
• Attempts to cure pAM1 failed, however a mutant with reduced plasmid content was obtained, which showed reduced ability to degrade the flavonoid rutinosides rutin and hesperidin [22].
• HPLC/UV (diode array detector) analysis demonstrated that hesperidin was the major flavanone and nobiletin and heptamethoxyflavone were the major polymethoxylated flavones [23].

Gene context of hesperidin

• Our data indicate hesperidin as a COX-2 and iNOS inhibitor, which might be related to the anti-inflammatory and anti-tumorigenic efficacies [24].
• Inhibition of inducible isoforms of cyclooxygenase and nitric oxide synthase by flavonoid hesperidin in mouse macrophage cell line [24].
• Male C57BL/KsJ-db/db mice (db/db mice, 5 wk old), an animal model for type 2 diabetes, were fed a nonpurified diet for 2 wk and then were fed an AIN-76 control diet or the control diet supplemented with hesperidin (0.2 g/kg diet) or naringin (0.2 g/kg diet) [3].
• Colony stimulating factor-inducing activity of hesperidin [25].
• Treatment with hesperidin suppressed production of PGE2, nitrogen dioxide (NO2), and expression of iNOS protein [24].

Analytical, diagnostic and therapeutic context of hesperidin

• Eriocitrin and hesperidin could be identified as characteristic flavanones and chiral separation of their diastereomers could be achieved according to the developed chiral method by capillary electrophoresis using a 0.2 M borate buffer at pH 10.0 and with 5 mM gamma-CD as chiral selector [26].
• CONCLUSIONS: A vascular protector such as micronized diosmine hesperidine with recommended corticosteroid premedication and benzopyrones may be useful in preventing and treating docetaxel-induced fluid retention [27].
• Determination of hesperidin in Pericarpium Citri Reticulatae by semi-micro HPLC with electrochemical detection [28].
• 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) [28].
• In the present study, we identified the chemical structures and concentrations of the major conjugated metabolites in rat plasma after oral administration of hesperidin [29].

References