Reference

∮ HEALTHY AGEING

1.Yeh, C. H., Shen, Z. Q., Wang, T. W., Kao, C. H., Teng, Y. C., Yeh, T. K., … & Tsai, T. F. (2022). Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice. Journal of biomedical science, 29(1), 1-21. https://doi.org/10.1186/s12929-022-00838-7

2.Yeh, C. H., Shen, Z. Q., Lin, C. C., Lu, C. K., & Tsai, T. F. (2022). Rejuvenation: Turning Back Time by Enhancing CISD2. International Journal of Molecular Sciences, 23(22), 14014.https://doi.org/10.3390/ijms232214014

3.Luo, Y., Fan, H., Tan, X., & Li, Z. (2021). Hesperetin rescues emotional memory and synaptic plasticity deficit in aged rats. Behavioral Neuroscience, 135(6), 721. https://doi.org/10.1037/bne0000475

4.Miler, M., Živanović, J., Ajdžanović, V., Oreščanin-Dušić, Z., Milenković, D., Konić-Ristić, A., … & Šošić-Jurjević, B. (2016). Citrus flavanones naringenin and hesperetin improve antioxidant status and membrane lipid compositions in the liver of old-aged Wistar rats. Experimental Gerontology, 84, 49-60. https://doi.org/10.1016/j.exger.2016.08.014

5.Kim, J. Y., Jung, K. J., Choi, J. S., & Chung, H. Y. (2006). Modulation of the age-related nuclear factor-κB (NF-κB) pathway by hesperetin. Aging Cell, 5(5), 401-411.https://doi.org/10.1111/j.1474-9726.2006.00233.x

∮ COGNITIVE & BRAIN HEALTH

Memory Health

1.Aranarochana, A., Kaewngam, S., Anosri, T., Sirichoat, A., Pannangrong, W., Wigmore, P., & Welbat, J. U. (2021). Hesperidin Reduces Memory Impairment Associated with Adult Rat Hippocampal Neurogenesis Triggered by Valproic Acid. Nutrients, 13(12), 4364.https://doi.org/10.3390/nu13124364

2.Moghaddam, A. H., & Zare, M. (2018). Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the elevated oxygen stress in rat model of Alzheimer’s disease. Biomedicine & Pharmacotherapy, 97, 1096-1101.https://doi.org/10.1016/j.biopha.2017.11.047

Neuroprotection

3.Antunes, M. S., Ladd, F. V. L., Ladd, A. A. B. L., Moreira, A. L., Boeira, S. P., & Cattelan Souza, L. (2021). Hesperidin protects against behavioral alterations and loss of dopaminergic neurons in 6-OHDA-lesioned mice: the role of mitochondrial dysfunction and apoptosis. Metabolic Brain Disease, 36(1), 153-167.https://doi.org/10.1007/s11011-020-00618-y

4.Khan, A., Ikram, M., Hahm, J. R., & Kim, M. O. (2020). Antioxidant and anti-inflammatory effects of citrus flavonoid hesperetin: special focus on neurological disorders. Antioxidants, 9(7), 609.https://doi.org/10.3390/antiox9070609

∮ CIRCULATION HEALTH

1.Nishimura, N., Iwase, S., Takumi, H., & Yamamoto, K. (2021). Gravity-Induced Lower-Leg Swelling Can Be Ameliorated by Ingestion of α-Glucosyl Hesperidin Beverage. Frontiers in physiology, 12, 749.https://doi.org/10.3389/fphys.2021.670640

2.Yamamoto, M., Jokura, H., Hashizume, K., Ominami, H., Shibuya, Y., Suzuki, A., … & Shimotoyodome, A. (2013). Hesperidin metabolite hesperetin-7-O-glucuronide, but not hesperetin-3′-O-glucuronide, exerts hypotensive, vasodilatory, and anti-inflammatory activities. Food & Function, 4(9), 1346-1351. https://doi.org/10.1039/C3FO60030K

3.Takumi, H., Fujishima, N., Shiraishi, K., Mori, Y., Ariyama, A., Kometani, T., … & Nadamoto, T. (2010). Effects of α-glucosylhesperidin on the peripheral body temperature and autonomic nervous system. Bioscience, biotechnology, and biochemistry, 74(4), 707-715. https://doi.org/10.1271/bbb.90742

∮ METABOLIC WELLNESS

1.Yang, H., Wang, Y., Xu, S., Ren, J., Tang, L., Gong, J., … & Su, D. (2022). Hesperetin, a Promising Treatment Option for Diabetes and Related Complications: A Literature Review. Journal of Agricultural and Food Chemistry, 70(28), 8582-8592.https://doi.org/10.1021/acs.jafc.2c03257

2.Rabbani, N., Xue, M., Weickert, M. O., & Thornalley, P. J. (2021). Reversal of Insulin Resistance in Overweight and Obese Subjects by trans-Resveratrol and Hesperetin Combination—Link to Dysglycemia, Blood Pressure, Dyslipidemia, and Low-Grade Inflammation. Nutrients, 13(7), 2374.https://doi.org/10.3390/nu13072374

3.Karim, N., Shishir, M. R. I., Gowd, V., & Chen, W. (2021). Hesperidin-An Emerging Bioactive Compound against Metabolic Diseases and Its Potential Biosynthesis Pathway in Microorganism. Food Reviews International, 1-23.https://doi.org/10.1080/87559129.2020.1858312

4.(Clinical)Pla-Pagà, L., Valls, R. M., Pedret, A., Calderón-Pérez, L., Llauradó, E., Companys, J., … & Solà, R. (2021). Effect of the consumption of hesperidin in orange juice on the transcriptomic profile of subjects with elevated blood pressure and stage 1 hypertension: A randomized controlled trial (CITRUS study). Clinical Nutrition, 40(12), 5812-5822.https://doi.org/10.1016/j.clnu.2021.10.009

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5.Akiyama, S., Katsumata, S. I., Suzuki, K., Ishimi, Y., Wu, J., & Uehara, M. (2009). Dietary hesperidin exerts hypoglycemic and hypolipidemic effects in streptozotocin-induced marginal type 1 diabetic rats. Journal of clinical biochemistry and nutrition, 46(1), 87-92.https://doi.org/10.3164/jcbn.09-82

6.Akiyama, S., Katsumata, S. I., Suzuki, K., Nakaya, Y., Ishimi, Y., & Uehara, M. (2009). Hypoglycemic and hypolipidemic effects of hesperidin and cyclodextrin-clathrated hesperetin in Goto-Kakizaki rats with type 2 diabetes. Bioscience, biotechnology, and biochemistry, 73(12), 2779-2782. https://doi.org/10.1271/bbb.90576

∮ CARDIOVASCULAR HEALTH

1.(Clinical)Valls, R. M., Pedret, A., Calderón-Pérez, L., Llaurado, E., Pla-Pagà, L., Companys, J., … & Sola, R. (2021). Hesperidin in orange juice improves human endothelial function in subjects with elevated blood pressure and stage 1 hypertension: A randomized, controlled trial (Citrus study). Journal of Functional Foods, 85, 104646.https://doi.org/10.1016/j.jff.2021.104646

2.Liu, P., Li, J., Liu, M., Zhang, M., Xue, Y., Zhang, Y., … & Chu, L. (2021). Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis. Biomedicine & Pharmacotherapy, 139, 111552.https://doi.org/10.1016/j.biopha.2021.111552

3.Velusamy, P., Mohan, T., Ravi, D. B., Kishore Kumar, S. N., Srinivasan, A., Chakrapani, L. N., … & Kalaiselvi, P. (2020). Targeting the Nrf2/ARE signalling pathway to mitigate isoproterenol-induced cardiac hypertrophy: plausible role of hesperetin in redox homeostasis. Oxidative medicine and cellular longevity, 2020. https://doi.org/10.1155/2020/9568278

4.Sugasawa, N., Katagi, A., Kurobe, H., Nakayama, T., Nishio, C., Takumi, H., … & Kitagawa, T. (2019). Inhibition of atherosclerotic plaque development by oral administration of α-glucosyl hesperidin and water-dispersible hesperetin in apolipoprotein E knockout mice. Journal of the American College of Nutrition, 38(1), 15-22.DOI:10.1080/07315724.2018.1468831

5.(Clinical)Morand, C., Dubray, C., Milenkovic, D., Lioger, D., Martin, J. F., Scalbert, A., & Mazur, A. (2011). Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers. The American journal of clinical nutrition, 93(1), 73-80. https://doi.org/10.3945/ajcn.110.004945

6.(Clinical)Rizza, S., Muniyappa, R., Iantorno, M., Kim, J. A., Chen, H., Pullikotil, P., … & 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. The Journal of Clinical Endocrinology & Metabolism, 96(5), E782-E792.https://doi.org/10.1210/jc.2010-2879

∮ IMMUNE HEALTH

1.Cheng, F. J., Huynh, T. K., Yang, C. S., Hu, D. W., Shen, Y. C., Tu, C. Y., … & Ho, C. Y. (2021). Hesperidin is a potential inhibitor against SARS-CoV-2 infection. Nutrients, 13(8), 2800.https://doi.org/10.3390/nu13082800

2.Miles, E. A., & Calder, P. C. (2021). Effects of citrus fruit juices and their bioactive components on inflammation and immunity: a narrative review. Frontiers in immunology, 12, 2558.https://doi.org/10.3389/fimmu.2021.712608

∮ MICROBIOME BALANCE

1.Estruel-Amades, S., Massot-Cladera, M., Pérez-Cano, F. J., Franch, À., Castell, M., & Camps-Bossacoma, M. (2019). Hesperidin effects on gut microbiota and gut-associated lymphoid tissue in healthy rats. Nutrients, 11(2), 324. https://doi.org/10.3390/nu11020324

2.Unno, T., Hisada, T., & Takahashi, S. (2015). Hesperetin modifies the composition of fecal microbiota and increases cecal levels of short-chain fatty acids in rats. Journal of agricultural and food chemistry, 63(36), 7952-7957. https://doi.org/10.1021/acs.jafc.5b02649

∮ EYE HEALTH

1.Nakazawa, Y., Doki, Y., Sugiyama, Y., Kobayashi, R., Nagai, N., Morisita, N., … & Tamura, H. (2021). Effect of Alpha-Glucosyl-Hesperidin Consumption on Lens Sclerosis and Presbyopia. Cells, 10(2), 382. https://doi.org/10.3390/cells10020382

2.Nakazawa, Y., Oka, M., Bando, M., & Takehana, M. (2015). Hesperetin prevents selenite-induced cataract in rats. Molecular vision, 21, 804. PMID: 26283862