2,711
Views
201
CrossRef citations to date
0
Altmetric
Articles

Health-promoting effects of the citrus flavanone hesperidin

&

References

  • Abuelsaad, A. S., Mohamed, I., Allam, G., and Al-Solumani, A. A. (2013). Antimicrobial and immunomodulating activities of hesperidin and ellagic acid against diarrheic Aeromonas hydrophila in a murine model. Life Sci. 93:714–722.
  • Ahmad, S. T., Arjumand, W., Nafees, S., Seth, A., Ali, N., Rashid, S., and Sultana, S. (2012). Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation. Toxicol. Lett. 208:149–161.
  • Ahmadi, A., Hosseinimehr, S. J., Naghshvar, F., Hajir, E., and Ghahremani, M. (2008). Chemoprotective effects of hesperidin against genotoxicity induced by cyclophosphamide in mice bone marrow cells. Arch. Pharm. Res. 31:794–797.
  • Akiyama, S., Katsumata, S., Suzuki, K., Ishimi, Y., Wu, J., and Uehara, M. (2010). Dietary hesperidin exerts hypoglycemic and hypolipidemic effects in streptozotocin-induced marginal type 1 diabetic rats. J. Clin. Biochem. Nutr. 46:87–92.
  • Akiyama, S., Katsumata, S., Suzuki, K., Nakaya, Y., Ishimi, Y., and Uehara, M. (2009). Hypoglycemic and hypolipidemic effects of hesperidin and cyclodextrin-clathrated hesperetin in Goto-Kakizaki rats with type 2 diabetes. Biosci. Biotechnol. Biochem. 73:2779–2782.
  • Allegra, C., Bartolo, M., Jr., Carioti, B., and Cassiani, D. (1995). An original microhaemorheological approach to the pharmacological effects of Daflon 500 mg in severe chronic venous insufficiency. Int. J. Microcirc. Clin. Exp. 15(Suppl. 1):50–54.
  • Amato, C. (1994). Advantage of a micronized flavonoidic fraction (Daflon 500 mg) in comparison with a nonmicronized diosmin. Angiology. 45:531–536.
  • American Diabetes, A. (2011). Diagnosis and classification of diabetes mellitus. Diabetes Care. 34(Suppl. 1):S62–S69.
  • Anandan, R., and Subramanian, P. (2012). Renal protective effect of hesperidin on gentamicin-induced acute nephrotoxicity in male Wistar albino rats. Redox. Rep. 17:219–226.
  • Andriantsitohaina, R., Duluc, L., Garcia-Rodriguez, J. C., Gil-del Valle, L., Guevara-Garcia, M., Simard, G., Soleti, R., Su, D. F., Velasquez-Perez, L., Wilson, J. X., and Laher, I. (2012). Systems biology of antioxidants. Clin. Sci. 123:173–192.
  • Arai, M., Matsumura, T., Tsuchiya, N., Sadakane, C., Inami, R., Suzuki, T., Yoshikawa, M., Imazeki, F., and Yokosuka, O. (2012). Rikkunshito improves the symptoms in patients with functional dyspepsia, accompanied by an increase in the level of plasma ghrelin. Hepato-Gastroenterology. 59:62–66.
  • Arts, I. C., and Hollman, P. C. (2005). Polyphenols and disease risk in epidemiologic studies. Am. J. Clin. Nutr. 81:317S–325S.
  • Baker, M. G., Kale, R., and Menken, M. (2002). The wall between neurology and psychiatry. Bmj. 324:1468–1469.
  • Balakrishnan, A., and Menon, V. P. (2007a). Antioxidant properties of hesperidin in nicotine-induced lung toxicity. Fundam. Clin. Pharmacol. 21:535–546.
  • Balakrishnan, A., and Menon, V. P. (2007b). Effect of hesperidin on matrix metalloproteinases and antioxidant status during nicotine-induced toxicity. Toxicology. 238:90–98.
  • Balakrishnan, A., and Menon, V. P. (2007c). Effect of hesperidin on nicotine toxicity and histopathological studies. Toxicol. Mech. Methods. 17:233–239.
  • Balakrishnan, A., and Menon, V. P. (2007d). Protective effect of hesperidin on nicotine induced toxicity in rats. Indian J. Exp. Biol. 45:194–202.
  • Bannasch, P., Mayer, D., and Hacker, H. J. (1980). Hepatocellular glycogenosis and hepatocarcinogenesis. Biochim. Biophys. Acta. 605:217–245.
  • Behar, A., Lagrue, G., Cohen-Boulakia, F., and Baillet, J. (1988). Study of capillary filtration by double labelling I131-albumin and Tc99m red cells. Application to the pharmacodynamic activity of Daflon 500 mg. Int. Angiol. 7:35–38.
  • Berhow, M. A. (1998). Flavonoid accumulation in tissue and cell culture. Studies in Citrus and other plant species. Adv. Exp. Med. Biol. 439:67–84.
  • Cai, H., and Harrison, D. G. (2000). Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress. Circ. Res. 87:840–844.
  • Carmichael, S. T. (2005). Rodent models of focal stroke: Size, mechanism, and purpose. Neuro Rx. 2:396–409.
  • Chanet, A., Milenkovic, D., Manach, C., Mazur, A., and Morand, C. (2012). Citrus flavanones: What is their role in cardiovascular protection? J. Agric. Food Chem. 60:8809–8822.
  • Chen, M., Gu, H., Ye, Y., Lin, B., Sun, L., Deng, W., Zhang, J., and Liu, J. (2010a). Protective effects of hesperidin against oxidative stress of tert-butyl hydroperoxide in human hepatocytes. Food Chem. Toxicol. 48:2980–2987.
  • Chen, M. C., Ye, Y. Y., Ji, G., and Liu, J. W. (2010b). Hesperidin upregulates heme oxygenase-1 to attenuate hydrogen peroxide-induced cell damage in hepatic L02 cells. J. Agric. Food Chem. 58:3330–3335.
  • Chiba, H., Kim, H., Matsumoto, A., Akiyama, S., Ishimi, Y., Suzuki, K., and Uehara, M. (2013). Hesperidin prevents androgen deficiency-induced bone loss in male mice. Phytother Res.
  • Chiba, H., Uehara, M., Wu, J., Wang, X., Masuyama, R., Suzuki, K., Kanazawa, K., and Ishimi, Y. (2003). Hesperidin, a citrus flavonoid, inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice. J. Nutr. 133:1892–1897.
  • Cospite, M. (1994). Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute hemorrhoids. Angiology. 45:566–573.
  • Darr, D., and Fridovich, I. (1994). Free radicals in cutaneous biology. J. Invest. Dermatol. 102:671–675.
  • Deanfield, J. E., Halcox, J. P., and Rabelink, T. J. (2007). Endothelial function and dysfunction: Testing and clinical relevance. Circulation. 115:1285–1295.
  • Demaerschalk, B. M., Hwang, H. M., and Leung, G. (2010). US cost burden of ischemic stroke: A systematic literature review. Am. J. Manag. Care. 16:525–533.
  • Demonty, I., Lin, Y., Zebregs, Y. E., Vermeer, M. A., van der Knaap, H. C., Jakel, M., and Trautwein, E. A. (2010). The citrus flavonoids hesperidin and naringin do not affect serum cholesterol in moderately hypercholesterolemic men and women. J. Nutr. 140:1615–1620.
  • Devore, E. E., Kang, J. H., Breteler, M. M., and Grodstein, F. (2012). Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann. Neurol. 72:135–143.
  • Duchene Marullaz, P., Amiel, M., and Barbe, R. (1988). Evaluation of the clinical pharmacological activity of a phlebotonic agent. Application to the study of Daflon 500 mg. Int. Angiol. 7:25–32.
  • El-Sayed el, S. M., Abo-Salem, O. M., Abd-Ellah, M. F., and Abd-Alla, G. M. (2008). Hesperidin, an antioxidant flavonoid, prevents acrylonitrile-induced oxidative stress in rat brain. J. Biochem. Mol. Toxicol. 22:268–273.
  • Elavarasan, J., Velusamy, P., Ganesan, T., Ramakrishnan, S. K., Rajasekaran, D., and Periandavan, K. (2012). Hesperidin-mediated expression of Nrf2 and upregulation of antioxidant status in senescent rat heart. J. Pharm. Pharmacol. 64:1472–1482.
  • Filho, C. B., Del Fabbro, L., de Gomes, M. G., Goes, A. T., Souza, L. C., Boeira, S. P., and Jesse, C. R. (2013). Kappa-opioid receptors mediate the antidepressant-like activity of hesperidin in the mouse forced swimming test. Eur. J. Pharmacol. 698:286–291.
  • Gandhi, C., Upaganalawar, A., and Balaraman, R. (2009). Protection against in vivo focal myocardial ischemia/reperfusion injury-induced arrhythmias and apoptosis by hesperidin. Free Radic. Res. 43:817–827.
  • Gao, X., Cassidy, A., Schwarzschild, M. A., Rimm, E. B., and Ascherio, A. (2012). Habitual intake of dietary flavonoids and risk of Parkinson disease. Neurology. 78:1138–1145.
  • Garg, A., Garg, S., Zaneveld, L. J., and Singla, A. K. (2001). Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. Phytother. Res. 15:655–669.
  • Gaur, V., Aggarwal, A., and Kumar, A. (2011). Possible nitric oxide mechanism in the protective effect of hesperidin against ischemic reperfusion cerebral injury in rats. Indian J. Exp. Biol. 49:609–618.
  • Gaur, V., and Kumar, A. (2010). Hesperidin pre-treatment attenuates NO-mediated cerebral ischemic reperfusion injury and memory dysfunction. Pharmacol. Rep. 62:635–648.
  • Geroulakos, G., and Nicolaides, A. N. (1994). Controlled studies of Daflon 500 mg in chronic venous insufficiency. Angiology. 45:549–553.
  • Ghorbani, A., Nazari, M., Jeddi-Tehrani, M., and Zand, H. (2012). The citrus flavonoid hesperidin induces p53 and inhibits NF-kappaB activation in order to trigger apoptosis in NALM-6 cells: Involvement of PPARgamma-dependent mechanism. Eur. J. Nutr. 51:39–46.
  • Godeberge, P. (1994). Daflon 500 mg in the treatment of hemorrhoidal disease: A demonstrated efficacy in comparison with placebo. Angiology. 45:574–578.
  • Gonzalez-Barrio, R., Trindade, L. M., Manzanares, P., de Graaff, L. H., Tomas-Barberan, F. A., and Espin, J. C. (2004). Production of bioavailable flavonoid glucosides in fruit juices and green tea by use of fungal alpha-L-rhamnosidases. J. Agric. Food Chem. 52:6136–6142.
  • Guardia, T., Rotelli, A. E., Juarez, A. O., and Pelzer, L. E. (2001). Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmaco. 56:683–687.
  • Guex, J. J., Enriquez Vega, D. M., Avril, L., Boussetta, S., and Taieb, C. (2009). Assessment of quality of life in Mexican patients suffering from chronic venous disorder:Impact of oral Ruscus aculeatus-hesperidin-methyl-chalcone-ascorbic acid treatment—‘QUALITY Study’. Phlebology. 24:157–165.
  • Guilhou, J. J., Dereure, O., Marzin, L., Ouvry, P., Zuccarelli, F., Debure, C., Van Landuyt, H., Gillet-Terver, M. N., Guillot, B., Levesque, H., Mignot, J., Pillion, G., Fevrier, B., and Dubeaux, D. (1997). Efficacy of Daflon 500 mg in venous leg ulcer healing: A double-blind, randomized, controlled versus placebo trial in 107 patients. Angiology. 48:77–85.
  • Ho, E., Karimi Galougahi, K., Liu, C. C., Bhindi, R., and Figtree, G. A. (2013). Biological markers of oxidative stress: Applications to cardiovascular research and practice. Redox. Biology. 1:483–491.
  • Horcajada, M. N., Habauzit, V., Trzeciakiewicz, A., Morand, C., Gil-Izquierdo, A., Mardon, J., Lebecque, P., Davicco, M. J., Chee, W. S., Coxam, V., and Offord, E. (2008). Hesperidin inhibits ovariectomized-induced osteopenia and shows differential effects on bone mass and strength in young and adult intact rats. J. Appl. Physiol. (1985). 104:648–654.
  • Hosseinimehr, S. J., Ahmadi, A., Beiki, D., Habibi, E., and Mahmoudzadeh, A. (2009a). Protective effects of hesperidin against genotoxicity induced by (99m)Tc-MIBI in human cultured lymphocyte cells. Nucl. Med. Biol. 36:863–867.
  • Hosseinimehr, S. J., Mahmoudzadeh, A., Ahmadi, A., Mohamadifar, S., and Akhlaghpoor, S. (2009b). Radioprotective effects of hesperidin against genotoxicity induced by gamma-irradiation in human lymphocytes. Mutagenesis. 24:233–235.
  • Huang, S. M., Tsai, S. Y., Lin, J. A., Wu, C. H., and Yen, G. C. (2012). Cytoprotective effects of hesperetin and hesperidin against amyloid beta-induced impairment of glucose transport through downregulation of neuronal autophagy. Mol. Nutr. Food Res. 56:601–609.
  • Hwang, S. L., Lin, J. A., Shih, P. H., Yeh, C. T., and Yen, G. C. (2012). Pro-cellular survival and neuroprotection of citrus flavonoid: The actions of hesperetin in PC12 cells. Food Funct. 3:1082–1090.
  • Hwang, S. L., and Yen, G. C. (2011). Effect of hesperetin against oxidative stress via ER- and TrkA-mediated actions in PC12 cells. J. Agric. Food Chem. 59:5779–5785.
  • Ibegbuna, V., Nicolaides, A. N., Sowade, O., Leon, M., and Geroulakos, G. (1997). Venous elasticity after treatment with Daflon 500 mg. Angiology. 48:45–49.
  • Ikemura, M., Sasaki, Y., Giddings, J. C., and Yamamoto, J. (2012). Preventive effects of hesperidin, glucosyl hesperidin and naringin on hypertension and cerebral thrombosis in stroke-prone spontaneously hypertensive rats. Phytother. Res. 26:1272–1277.
  • Jin, M. J., Kim, U., Kim, I. S., Kim, Y., Kim, D. H., Han, S. B., Kim, D. H., Kwon, O. S., and Yoo, H. H. (2010). Effects of gut microflora on pharmacokinetics of hesperidin: A study on non-antibiotic and pseudo-germ-free rats. J. Toxicol. Environ. Health A. 73:1441–1450.
  • Jin, S., Zhou, B., and Luo, D. (2011). Hesperidin promotes cyclobutane pyrimidine dimer repair in UVB-exposed mice epidermis. Ir. J. Med. Sci. 180:709–714.
  • Jung, U. J., Lee, M. K., Jeong, K. S., and Choi, M. S. (2004). The hypoglycemic effects of hesperidin and naringin are partly mediated by hepatic glucose-regulating enzymes in C57BL/KsJ-db/db mice. J. Nutr. 134:2499–2503.
  • Kalpana, K. B., Devipriya, N., Srinivasan, M., and Menon, V. P. (2009). Investigation of the radioprotective efficacy of hesperidin against gamma-radiation induced cellular damage in cultured human peripheral blood lymphocytes. Mutat. Res. 676:54–61.
  • Kamaraj, S., Anandakumar, P., Jagan, S., Ramakrishnan, G., and Devaki, T. (2010). Modulatory effect of hesperidin on benzo(a)pyrene induced experimental lung carcinogenesis with reference to COX-2, MMP-2 and MMP-9. Eur. J. Pharmacol. 649:320–327.
  • Kamaraj, S., Anandakumar, P., Jagan, S., Ramakrishnan, G., and Devaki, T. (2011). Hesperidin attenuates mitochondrial dysfunction during benzo(a)pyrene-induced lung carcinogenesis in mice. Fundam. Clin. Pharmacol. 25:91–98.
  • Kamaraj, S., Ramakrishnan, G., Anandakumar, P., Jagan, S., and Devaki, T. (2009). Antioxidant and anticancer efficacy of hesperidin in benzo(a)pyrene induced lung carcinogenesis in mice. Invest. New Drugs. 27:214–222.
  • Kamisli, S., Ciftci, O., Kaya, K., Cetin, A., Kamisli, O., and Ozcan, C. (2013). Hesperidin protects brain and sciatic nerve tissues against cisplatin-induced oxidative, histological and electromyographical side effects in rats. Toxicol. Ind. Health.
  • Kaur, G., Tirkey, N., and Chopra, K. (2006). Beneficial effect of hesperidin on lipopolysaccharide-induced hepatotoxicity. Toxicology. 226:152–160.
  • Kim, M., Kometani, T., Okada, S., and Shimuzu, M. (1999). Permeation of hesperidin glycosides across Caco-2 cell monolayers via the paracellular pathway. Biosci. Biotechnol. Biochem. 63:2183–2188.
  • Kim, S. H., Kim, B. K., and Lee, Y. C. (2011). Antiasthmatic effects of hesperidin, a potential Th2 cytokine antagonist, in a mouse model of allergic asthma. Mediators Inflamm. 2011:485402.
  • Knekt, P., Kumpulainen, J., Jarvinen, R., Rissanen, H., Heliovaara, M., Reunanen, A., Hakulinen, T., and Aromaa, A. (2002). Flavonoid intake and risk of chronic diseases. Am. J. Clin. Nutr. 76:560–568.
  • Kobayashi, S., Tanabe, S., Sugiyama, M., and Konishi, Y. (2008). Transepithelial transport of hesperetin and hesperidin in intestinal Caco-2 cell monolayers. Biochim. Biophys. Acta. 1778:33–41.
  • Kremer, B., Goldberg, P., Andrew, S. E., Theilmann, J., Telenius, H., Zeisler, J., Squitieri, F., Lin, B., Bassett, A., Almqvist, E., et al. (1994). A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats. N. Engl. J. Med. 330:1401–1406.
  • Kumar, B., Gupta, S. K., Srinivasan, B. P., Nag, T. C., Srivastava, S., Saxena, R., and Jha, K. A. (2013b). Hesperetin rescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic rats. Microvasc. Res. 87:65–74.
  • Kumar, P., and Kumar, A. (2010). Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington's like symptoms in rats: Possible role of nitric oxide. Behav. Brain Res. 206:38–46.
  • Kumar, A., Lalitha, S., and Mishra, J. (2013a). Possible nitric oxide mechanism in the protective effect of hesperidin against pentylenetetrazole (PTZ)-induced kindling and associated cognitive dysfunction in mice. Epilepsy. Behav. 29:103–111.
  • Kurowska, E. M., Spence, J. D., Jordan, J., Wetmore, S., Freeman, D. J., Piche, L. A., and Serratore, P. (2000). HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia. Am. J. Clin. Nutr. 72:1095–1100.
  • Kusunoki, H., Haruma, K., Hata, J., Ishii, M., Kamada, T., Yamashita, N., Honda, K., Inoue, K., Imamura, H., Manabe, N., Shiotani, A., and Tsunoda, T. (2010). Efficacy of Rikkunshito, a traditional Japanese medicine (Kampo), in treating functional dyspepsia. Int. Med. 49:2195–2202.
  • Lai, M. C., and Yang, S. N. (2011). Perinatal hypoxic-ischemic encephalopathy. J. Biomed. Biotechnol. 2011:609813.
  • Laurent, R., Gilly, R., and Frileux, C. (1988). Clinical evaluation of a venotropic drug in man. Example of Daflon 500 mg. Int. Angiol. 7:39–43.
  • Le Devehat, C., Khodabandehlou, T., Vimeux, M., and Kempf, C. (1997). Evaluation of haemorheological and microcirculatory disturbances in chronic venous insufficiency: Activity of Daflon 500 mg. Int. J. Microcirc. Clin. Exp. 17(Suppl. 1):27–33.
  • Lee, C. J., Wilson, L., Jordan, M. A., Nguyen, V., Tang, J., and Smiyun, G. (2010a). Hesperidin suppressed proliferations of both human breast cancer and androgen-dependent prostate cancer cells. Phytother. Res. 24(Suppl. 1):S15–S19.
  • Lee, K. A., Lee, S. H., Lee, Y. J., Baeg, S. M., and Shim, J. H. (2012). Hesperidin Induces Apoptosis by Inhibiting Sp1 and Its Regulatory Protein in MSTO-211H Cells. Biomol. Ther. (Seoul). 20:273–279.
  • Lee, K. H., Yeh, M. H., Kao, S. T., Hung, C. M., Liu, C. J., Huang, Y. Y., and Yeh, C. C. (2010b). The inhibitory effect of hesperidin on tumor cell invasiveness occurs via suppression of activator protein 1 and nuclear factor-kappaB in human hepatocellular carcinoma cells. Toxicol. Lett. 194:42–49.
  • Lee, Y. R., Jung, J. H., and Kim, H. S. (2011). Hesperidin partially restores impaired immune and nutritional function in irradiated mice. J. Med. Food. 14:475–482.
  • Li, R., Cai, L., Xie, X. F., Yang, F., and Li, J. (2010). Hesperidin suppresses adjuvant arthritis in rats by inhibiting synoviocyte activity. Phytother. Res. 24(Suppl 1):S71–S76.
  • Li, C., Ebrahimi, A., and Schluesener, H. (2013a). Drug pipeline in neurodegeneration based on transgenic mice models of Alzheimer's disease. Ageing Res. Rev. 12:116–140.
  • Li, R., Li, J., Cai, L., Hu, C. M., and Zhang, L. (2008a). Suppression of adjuvant arthritis by hesperidin in rats and its mechanisms. J. Pharm. Pharmacol. 60:221–228.
  • Li, Y. M., Li, X. M., Li, G. M., Du, W. C., Zhang, J., Li, W. X., Xu, J., Hu, M., and Zhu, Z. (2008b). In vivo pharmacokinetics of hesperidin are affected by treatment with glucosidase-like BglA protein isolated from yeasts. J. Agric. Food Chem. 56:5550–5557.
  • Li, C., Yuan, K., and Schluesener, H. (2013b). Impact of minocycline on neurodegenerative diseases in rodents: A meta-analysis. Rev. Neurosci. 24:553–562.
  • Mahmoud, A. M., Ashour, M. B., Abdel-Moneim, A., and Ahmed, O. M. (2012). Hesperidin and naringin attenuate hyperglycemia-mediated oxidative stress and proinflammatory cytokine production in high fat ed/streptozotocin-induced type 2 diabetic rats. J. Diab. Complicat. 26:483–490.
  • Manach, C., Morand, C., Gil-Izquierdo, A., Bouteloup-Demange, C., and Remesy, C. (2003). Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice. Eur. J. Clin. Nutr. 57:235–242.
  • Manthey, J. A., and Grohmann, K. (1998). Flavonoids of the orange subfamily Aurantioideae. Adv. Exp. Med. Biol. 439:85–101.
  • Martinez, M. C., Fernandez, S. P., Loscalzo, L. M., Wasowski, C., Paladini, A. C., Marder, M., Medina, J. H., and Viola, H. (2009). Hesperidin, a flavonoid glycoside with sedative effect, decreases brain pERK1/2 levels in mice. Pharmacol. Biochem. Behav. 92:291–296.
  • Menze, E. T., Tadros, M. G., Abdel-Tawab, A. M., and Khalifa, A. E. (2012). Potential neuroprotective effects of hesperidin on 3-nitropropionic acid-induced neurotoxicity in rats. Neurotoxicology. 33:1265–1275.
  • Meshikhes, A. W. (2002). Efficacy of Daflon in the treatment of hemorrhoids. Saudi Medical Journal. 23:1496–1498.
  • Meshikhes, A. W. (2004). Daflon for haemorrhoids: A prospective, multi-centre observational study. Surg. J. R. Coll. Surg. E. I. 2:335–338, 361.
  • Milenkovic, D., Deval, C., Dubray, C., Mazur, A., and Morand, C. (2011). Hesperidin displays relevant role in the nutrigenomic effect of orange juice on blood leukocytes in human volunteers: A randomized controlled cross-over study. PLoS One. 6:e26669.
  • Miwa, Y., Yamada, M., Sunayama, T., Mitsuzumi, H., Tsuzaki, Y., Chaen, H., Mishima, Y., and Kibata, M. (2004). Effects of glucosyl hesperidin on serum lipids in hyperlipidemic subjects: Preferential reduction in elevated serum triglyceride level. J. Nutr. Sci. Vitaminol (Tokyo). 50:211–218.
  • Molina-Jimenez, M. F., Sanchez-Reus, M. I., Andres, D., Cascales, M., and Benedi, J. (2004). Neuroprotective effect of fraxetin and myricetin against rotenone-induced apoptosis in neuroblastoma cells. Brain Res. 1009:9–16.
  • Moon, P. D., and Kim, H. M. (2012). Antiinflammatory effects of traditional Korean medicine, JinPi-tang and its active ingredient, hesperidin in HaCaT cells. Phytother. Res. 26:657–662.
  • Morand, C., Dubray, C., Milenkovic, D., Lioger, D., Martin, J. F., Scalbert, A., and Mazur, A. (2011). Hesperidin contributes to the vascular protective effects of orange juice: A randomized crossover study in healthy volunteers. Am. J. Clin. Nutr. 93:73–80.
  • Moss, S. E., Klein, R., and Klein, B. E. (1998). The 14-year incidence of visual loss in a diabetic population. Ophthalmology. 105:998–1003.
  • Mueller, C. F., Laude, K., McNally, J. S., and Harrison, D. G. (2005). ATVB in focus: Redox mechanisms in blood vessels. Arterioscler. Thromb. Vasc. Biol. 25:274–278.
  • Nandakumar, N., and Balasubramanian, M. P. (2011). Hesperidin protects renal and hepatic tissues against free radical-mediated oxidative stress during DMBA-induced experimental breast cancer. J. Environ. Pathol. Toxicol. Oncol. 30:283–300.
  • Nandakumar, N., and Balasubramanian, M. P. (2012). Hesperidin a citrus bioflavonoid modulates hepatic biotransformation enzymes and enhances intrinsic antioxidants in experimental breast cancer rats challenged with 7, 12-dimethylbenz (a) anthracene. J. Exp. Ther. Oncol. 9:321–335.
  • Nandakumar, N., Jayaprakash, R., and Balasubramanian, M. P. (2012). Influence of hesperidin on renal cell surface glycoprotein content, nucleic acids, lysosomal enzymes and macromolecules against 7, 12-dimethylbenz [a] anthracene induced experimental breast carcinoma. J. Exp. Ther. Oncol. 9:265–280.
  • Nandakumar, N., Rengarajan, T., Balamurugan, A., and Balasubramanian, M. (2013). Modulating effects of hesperidin on key carbohydrate-metabolizing enzymes, lipid profile, and membrane-bound adenosine triphosphatases against 7,12-dimethylbenz(a)anthracene-induced breast carcinogenesis. Hum. Exp. Toxicol.
  • Nielsen, I. L., Chee, W. S., Poulsen, L., Offord-Cavin, E., Rasmussen, S. E., Frederiksen, H., Enslen, M., Barron, D., Horcajada, M. N., and Williamson, G. (2006). Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: A randomized, double-blind, crossover trial. J. Nutr. 136:404–408.
  • Nones, J., Spohr, T. C., and Gomes, F. C. (2011). Hesperidin, a flavone glycoside, as mediator of neuronal survival. Neurochem. Res. 36:1776–1784.
  • Nones, J., Spohr, T. C., and Gomes, F. C. (2012). Effects of the flavonoid hesperidin in cerebral cortical progenitors in vitro: Indirect action through astrocytes. Int. J. Dev. Neurosci. 30:303–313.
  • Ohtsuki, K., Abe, A., Mitsuzuwi, H., Kondo, M., Uemura, K., Iwasaki, Y., and Kondo, Y. (2002). Effects of long-term administration of hesperidin and glucosyl hesperidin to spontaneously hypertensive rats. J. Nutr. Sci. Vitaminol. (Tokyo). 48:420–422.
  • Ohtsuki, K., Abe, A., Mitsuzumi, H., Kondo, M., Uemura, K., Iwasaki, Y., and Kondo, Y. (2003). Glucosyl hesperidin improves serum cholesterol composition and inhibits hypertrophy in vasculature. J. Nutr. Sci. Vitaminol. (Tokyo). 49:447–450.
  • Okuno, S., Hirayama, K., Inoue, J., Yamasaki, K., Kawahara, R., Yokoi, T., Saeki, N., and Funato, T. (2008). [Effects of rikkunshito on the postoperative nausea and vomiting (PONV) after laparoscopic gynecological surgery]. Masui. Jpn J. Anesthesiol. 57:1502–1509.
  • Ortega, A. D., Sanchez-Arago, M., Giner-Sanchez, D., Sanchez-Cenizo, L., Willers, I., and Cuezva, J. M. (2009). Glucose avidity of carcinomas. Cancer Lett. 276:125–135.
  • Park, H. J., Kim, M. J., Ha, E., and Chung, J. H. (2008). Apoptotic effect of hesperidin through caspase3 activation in human colon cancer cells, SNU-C4. Phytomedicine. 15:147–151.
  • Pecking, A. P. (1995). Evaluation by lymphoscintigraphy of the effect of a micronized flavonoid fraction (Daflon 500 mg) in the treatment of upper limb lymphedema. Int. Angiol. 14:39–43.
  • Pecking, A. P., Fevrier, B., Wargon, C., and Pillion, G. (1997). Efficacy of Daflon 500 mg in the treatment of lymphedema (secondary to conventional therapy of breast cancer). Angiology. 48:93–98.
  • Peterson, J. J., Dwyer, J. T., Beecher, G. R., Bhagwat, S. A., Gebhardt, S. E., Haytowitz, D. B., and Holden, J. M. (2006). Flavanones in oranges, tangerines (mandarins), tangors, and tangelos: A compilation and review of the data from the analytical literature. J. Food Composit. Anal. 19:S66–S73.
  • Petrova, A., Davids, L. M., Rautenbach, F., and Marnewick, J. L. (2011). Photoprotection by honeybush extracts, hesperidin and mangiferin against UVB-induced skin damage in SKH-1 mice. J. Photochem. Photobiol. B. 103:126–139.
  • Pradeep, K., Ko, K. C., Choi, M. H., Kang, J. A., Chung, Y. J., and Park, S. H. (2012). Protective effect of hesperidin, a citrus flavanoglycone, against gamma-radiation-induced tissue damage in Sprague–Dawley rats. J. Med. Food. 15:419–427.
  • Pradeep, K., Park, S. H., and Ko, K. C. (2008). Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague–Dawley rats. Eur. J. Pharmacol. 587:273–280.
  • Radad, K., Rausch, W. D., and Gille, G. (2006). Rotenone induces cell death in primary dopaminergic culture by increasing ROS production and inhibiting mitochondrial respiration. Neurochem. Int. 49:379–386.
  • Raza, S. S., Khan, M. M., Ahmad, A., Ashafaq, M., Khuwaja, G., Tabassum, R., Javed, H., Siddiqui, M. S., Safhi, M. M., and Islam, F. (2011). Hesperidin ameliorates functional and histological outcome and reduces neuroinflammation in experimental stroke. Brain Res. 1420:93–105.
  • Rizza, S., Muniyappa, R., Iantorno, M., Kim, J. A., Chen, H., Pullikotil, P., Senese, N., Tesauro, M., Lauro, D., Cardillo, C., and Quon, M. J. (2011). Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome. J. Clin. Endocrinol. Metab. 96:E782–E792.
  • Rong, Z., Pan, R., Xu, Y., Zhang, C., Cao, Y., and Liu, D. (2013). Hesperidin pretreatment protects hypoxia-ischemic brain injury in neonatal rat. Neuroscience. 255:292–299.
  • Roztocil, K., Stvrtinova, V., and Strejcek, J. (2003). Efficacy of a 6-month treatment with Daflon 500 mg in patients with venous leg ulcers associated with chronic venous insufficiency. Int. Angiol. 22:24–31.
  • Saha, R. K., Takahashi, T., and Suzuki, T. (2009). Glucosyl hesperidin prevents influenza a virus replication in vitro by inhibition of viral sialidase. Biol. Pharm. Bull. 32:1188–1192.
  • Sahu, B. D., Kuncha, M., Sindhura, G. J., and Sistla, R. (2013). Hesperidin attenuates cisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA damage. Phytomedicine. 20:453–460.
  • Said, U. Z., Saada, H. N., Abd-Alla, M. S., Elsayed, M. E., and Amin, A. M. (2012). Hesperidin attenuates brain biochemical changes of irradiated rats. Int. J. Radiat. Biol. 88:613–618.
  • Saiprasad, G., Chitra, P., Manikandan, R., and Sudhandiran, G. (2013). Hesperidin alleviates oxidative stress and downregulates the expressions of proliferative and inflammatory markers in azoxymethane-induced experimental colon carcinogenesis in mice. Inflamm. Res. 62:425–440.
  • Selvaraj, P., and Pugalendi, K. V. (2010). Hesperidin, a flavanone glycoside, on lipid peroxidation and antioxidant status in experimental myocardial ischemic rats. Redox. Rep. 15:217–223.
  • Selvaraj, P., and Pugalendi, K. V. (2012). Efficacy of hesperidin on plasma, heart and liver tissue lipids in rats subjected to isoproterenol-induced cardiotoxicity. Exp. Toxicol. Pathol. 64:449–452.
  • Shi, X., Liao, S., Mi, H., Guo, C., Qi, D., Li, F., Zhang, C., and Yang, Z. (2012). Hesperidin prevents retinal and plasma abnormalities in streptozotocin-induced diabetic rats. Molecules. 17:12868–12881.
  • Shiratori, M., Shoji, T., Kanazawa, M., Hongo, M., and Fukudo, S. (2011). Effect of rikkunshito on gastric sensorimotor function under distention. Neurogastroenterol. Motil. 23:323–329, e155–e326.
  • Simonian, N. A., and Coyle, J. T. (1996). Oxidative stress in neurodegenerative diseases. Ann. Rev. Pharmacol. Toxicol. 36:83–106.
  • Simsek, M., Burak, F., and Taskin, O. (2007). Effects of micronized purified flavonoid fraction (Daflon) on pelvic pain in women with laparoscopically diagnosed pelvic congestion syndrome: A randomized crossover trial. Clin. Exp. Obstet. Gynecol. 34:96–98.
  • Smith, G. D., Shipley, M. J., Marmot, M. G., and Rose, G. (1992). Plasma cholesterol concentration and mortality. The whitehall study. JAMA. 267:70–76.
  • Sonntag, V. C. (1987). The Chemical Basis of Radiation Biology. London: Taylor and Francis.
  • Souza, L. C., de Gomes, M. G., Goes, A. T., Del Fabbro, L., Filho, C. B., Boeira, S. P., and Jesse, C. R. (2013). Evidence for the involvement of the serotonergic 5-HT(1A) receptors in the antidepressant-like effect caused by hesperidin in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry. 40:103–109.
  • Takahashi, T., Endo, S., Nakajima, K., Souma, Y., and Nishida, T. (2009). Effect of rikkunshito, a chinese herbal medicine, on stasis in patients after pylorus-preserving gastrectomy. World J Surg. 33:296–302.
  • Takiguchi, S., Hiura, Y., Takahashi, T., Kurokawa, Y., Yamasaki, M., Nakajima, K., Miyata, H., Mori, M., Hosoda, H., Kangawa, K., and Doki, Y. (2013). Effect of rikkunshito, a Japanese herbal medicine, on gastrointestinal symptoms and ghrelin levels in gastric cancer patients after gastrectomy. Gastric Cancer. 16:167–174.
  • Tamilselvam, K., Braidy, N., Manivasagam, T., Essa, M., Prasad, N. R., Karthikeyan, S., Thenmozhi, A. J., Selvaraju, S., and Guillemin, G. J. (2013). Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson's disease. Oxid. Med. Cell. Longev. 2013:102741.
  • Tanaka, T., Makita, H., Kawabata, K., Mori, H., Kakumoto, M., Satoh, K., Hara, A., Sumida, T., and Ogawa, H. (1997). Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin. Carcinogenesis. 18:957–965.
  • Thanapongsathorn, W., and Vajrabukka, T. (1992). Clinical trial of oral diosmin (Daflon) in the treatment of hemorrhoids. Dis Colon. Rectum. 35:1085–1088.
  • Tominaga, K., Iwakiri, R., Fujimoto, K., Fujiwara, Y., Tanaka, M., Shimoyama, Y., Umegaki, E., Higuchi, K., Kusano, M., Arakawa, T., and Group, G. S. (2012). Rikkunshito improves symptoms in PPI-refractory GERD patients: A prospective, randomized, multicenter trial in Japan. J. Gastroenterol. 47:284–292.
  • Tsimoyiannis, E. C., Floras, G., Antoniou, N., Papanikolaou, N., Siakas, P., and Tassis, A. (1996). Low-molecular-weight heparins and Daflon for prevention of postoperative thromboembolism. World J Surg. 20:968–971; discussion 972.
  • Umar, S., Kumar, A., Sajad, M., Zargan, J., Ansari, M., Ahmad, S., Katiyar, C. K., and Khan, H. A. (2013). Hesperidin inhibits collagen-induced arthritis possibly through suppression of free radical load and reduction in neutrophil activation and infiltration. Rheumatol. Int. 33:657–663.
  • Viswanatha, G. L., Shylaja, H., Sandeep Rao, K. S., Santhosh Kumar, V. R., and Jagadeesh, M. (2012). Hesperidin ameliorates immobilization-stress-induced behavioral and biochemical alterations and mitochondrial dysfunction in mice by modulating nitrergic pathway. ISRN Pharmacol. 2012:479570.
  • Wang, X., Hasegawa, J., Kitamura, Y., Wang, Z., Matsuda, A., Shinoda, W., Miura, N., and Kimura, K. (2011). Effects of hesperidin on the progression of hypercholesterolemia and fatty liver induced by high-cholesterol diet in rats. J. Pharmacol. Sci. 117:129–138.
  • Wang, D. M., Li, S. Q., Zhu, X. Y., Wang, Y., Wu, W. L., and Zhang, X. J. (2013). Protective effects of hesperidin against amyloid-beta (Abeta) induced neurotoxicity through the voltage dependent anion channel 1 (VDAC1)-mediated mitochondrial apoptotic pathway in PC12 cells. Neurochem. Res. 38:1034–1044.
  • Wasowski, C., Loscalzo, L. M., Higgs, J., and Marder, M. (2012). Chronic intraperitoneal and oral treatments with hesperidin induce central nervous system effects in mice. Phytother. Res. 26:308–312.
  • Wei, D., Ci, X., Chu, X., Wei, M., Hua, S., and Deng, X. (2012). Hesperidin suppresses ovalbumin-induced airway inflammation in a mouse allergic asthma model. Inflammation. 35:114–121.
  • Xu, L., Yang, Z. L., Li, P., and Zhou, Y. Q. (2009). Modulating effect of Hesperidin on experimental murine colitis induced by dextran sulfate sodium. Phytomedicine. 16:989–995.
  • Yamada, M., Tanabe, F., Arai, N., Mitsuzumi, H., Miwa, Y., Kubota, M., Chaen, H., and Kibata, M. (2006). Bioavailability of glucosyl hesperidin in rats. Biosci. Biotechnol. Biochem. 70:1386–1394.
  • Yamamoto, M., Jokura, H., Hashizume, K., Ominami, H., Shibuya, Y., Suzuki, A., Hase, T., and Shimotoyodome, A. (2013). Hesperidin metabolite hesperetin-7-O-glucuronide, but not hesperetin-3′-O-glucuronide, exerts hypotensive, vasodilatory, and anti-inflammatory activities. Food Funct. 4:1346–1351.
  • Yamamoto, M., Suzuki, A., Jokura, H., Yamamoto, N., and Hase, T. (2008b). Glucosyl hesperidin prevents endothelial dysfunction and oxidative stress in spontaneously hypertensive rats. Nutrition. 24:470–476.
  • Yamamoto, M., Suzuki, A., and Hase, T. (2008a). Short-term effects of glucosyl hesperidin and hesperetin on blood pressure and vascular endothelial function in spontaneously hypertensive rats. J. Nutr. Sci. Vitaminol. (Tokyo). 54:95–98.
  • Yeh, M. H., Kao, S. T., Hung, C. M., Liu, C. J., Lee, K. H., and Yeh, C. C. (2009). Hesperidin inhibited acetaldehyde-induced matrix metalloproteinase-9 gene expression in human hepatocellular carcinoma cells. Toxicol. Lett. 184:204–210.
  • Yeh, C. C., Kao, S. J., Lin, C. C., Wang, S. D., Liu, C. J., and Kao, S. T. (2007). The immunomodulation of endotoxin-induced acute lung injury by hesperidin in vivo and in vitro. Life Sci. 80:1821–1831.
  • Youdim, K. A., Dobbie, M. S., Kuhnle, G., Proteggente, A. R., Abbott, N. J., and Rice-Evans, C. (2003). Interaction between flavonoids and the blood-brain barrier: In vitro studies. J. Neurochem. 85:180–192.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.