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Current Bioactive Compounds

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Mini-Review Article

Potential of Hesperidin in the Medicinal Field

Author(s): Dharmendra Kumar, Yadu Nandan Dey*, Siddhartha Das Pramanik, Laliteshwar Pratap Singh, Malarvili Selvaraja and Mogana Rajagopal

Volume 19, Issue 5, 2023

Published on: 08 December, 2022

Article ID: e201022210217 Pages: 9

DOI: 10.2174/1573407219666221020101834

Price: $65

Abstract

Hesperidin has gained major interest recently due to the outbreak of COVID-19. The traction has led to more research being conducted on the compound hesperidin. Recent studies have shown its anti-inflammatory and anti-viral attributes, which have beneficial effects on severe acute respiratory syndrome (SARS-CoV-2). Hesperidin has also shown unique effects on the protein of SARS-CoV-2, which lead to a good preventative measure for SARS-CoV-2. Hesperidin also causes a suppression of appetite, which helps to combat obesity through the release of cholecystokinin. Furthermore, hesperidin has shown cardioprotective properties, which cause an increase in plasma high-density lipoprotein levels and a decrease in plasma low-density lipoprotein levels. Hesperidin is also used in combination with the Japanese herb Rikkunshito, which has shown potential in a discovery of a new drug for gastrointestinal motility as hesperidin can depolarize pacemaker potential in interstitial cells of Cajal (ICC). The chemo-preventive effects of hesperidin are caused by its antioxidant effect, which may prevent tissue necrosis due to oxidative stress. The photo-protective effect of hesperidin can reduce the damage to the skin caused by UV rays. Hesperidin also possesses wound-healing properties.

Keywords: Anti-inflammatory, chemo-preventive effects, hesperidin, LDL levels, SARS-CoV-2, cardioprotective properties.

Graphical Abstract

[1]
Zanwar, A.A.; Badole, S.L.; Shende, P.S.; Hegde, M.V.; Bodhankar, S.L. Cardiovascular effects of hesperidin: A flavanone glycoside.In: Polyphenols in Human Health and Disease, 1st ed; Watson, R.R.; Preedy, V.R.; Zibadi,, S., Eds.; Academic Press: In Cambridge, 2014, pp. 989-992.
[2]
Mas-Capdevila, A.; Teichenne, J.; Domenech-Coca, C.; Caimari, A.; Del Bas, J.M.; Escoté, X.; Crescenti, A. Effect of hesperidin on cardiovascular disease risk factors: The role of intestinal microbiota on hesperidin bioavailability. Nutrients, 2020, 12(5), 1488.
[http://dx.doi.org/10.3390/nu12051488] [PMID: 32443766]
[3]
Yao, L.H.; Jiang, Y.M.; Shi, J.; Tomás-Barberán, F.A.; Datta, N.; Singanusong, R.; Chen, S.S. Flavonoids in food and their health benefits. Plant Foods Hum. Nutr., 2004, 59(3), 113-122.
[http://dx.doi.org/10.1007/s11130-004-0049-7] [PMID: 15678717]
[4]
Hwang, S.L.; Shih, P.H.; Yen, G.C. Citrus flavonoids and effects in dementia and age-related cognitive decline.Eds; Kolasa, K. In: Diet and Nutrition in Dementia and Cognitive Decline, 1st ed; Academic Press, 2015, pp. 869-878.
[http://dx.doi.org/10.1016/B978-0-12-407824-6.00080-X]
[5]
Iranshahi, M.; Rezaee, R.; Parhiz, H.; Roohbakhsh, A.; Soltani, F. Protective effects of flavonoids against microbes and toxins: The cases of hesperidin and hesperetin. Life Sci., 2015, 137(37), 125-132.
[http://dx.doi.org/10.1016/j.lfs.2015.07.014] [PMID: 26188593]
[6]
Singh, V.K.; Seed, T.M. Pharmacological management of ionizing radiation injuries: Current and prospective agents and targeted organ systems. Expert Opin. Pharmacother., 2020, 21(3), 317-337.
[http://dx.doi.org/10.1080/14656566.2019.1702968] [PMID: 31928256]
[7]
Das, S.; Sarmah, S.; Lyndem, S.; Roy, S.A. An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study. J. Biomol. Struct. Dyn., 2021, 39(9), 3347-3357.
[PMID: 32362245]
[8]
Haggag, Y.A.; El-Ashmawy, N.E.; Okasha, K.M. Is hesperidin essential for prophylaxis and treatment of COVID-19 Infection? Med. Hypotheses, 2020, 144109957
[http://dx.doi.org/10.1016/j.mehy.2020.109957] [PMID: 32531538]
[9]
Bellavite, P.; Donzelli, A. Hesperidin and SARS-CoV-2: New light on the healthy function of citrus fruits. Antioxidants, 2020, 9(8), 742.
[http://dx.doi.org/10.3390/antiox9080742] [PMID: 32823497]
[10]
Huang, L.; Shi, Y.; Gong, B.; Jiang, L.; Liu, X.; Yang, J.; Tang, J.; You, C.; Jiang, Q.; Long, B.; Zeng, T. Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19. MedRxiv, 2020.
[http://dx.doi.org/10.1101/2020.03.15.20033472]
[11]
Coperchini, F.; Chiovato, L.; Croce, L.; Magri, F.; Rotondi, M. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev., 2020, 53, 25-32.
[http://dx.doi.org/10.1016/j.cytogfr.2020.05.003] [PMID: 32446778]
[12]
Meneguzzo, F.; Ciriminna, R.; Zabini, F.; Pagliaro, M. Review of evidence available on hesperidin-rich products as potential tools against COVID-19 and hydrodynamic cavitation-based extraction as a method of increasing their production. Processes , 2020, 8(5), 549.
[http://dx.doi.org/10.3390/pr8050549]
[13]
Smith, J.D.; Fu, E.; Kobayashi, M.A. Prevention and management of childhood obesity and its psychological and health comorbidities. Annu. Rev. Clin. Psychol., 2020, 16(1), 351-378.
[http://dx.doi.org/10.1146/annurev-clinpsy-100219-060201] [PMID: 32097572]
[14]
Xiong, H.; Wang, J.; Ran, Q.; Lou, G.; Peng, C.; Gan, Q.; Hu, J.; Sun, J.; Yao, R.; Huang, Q. Hesperidin: A therapeutic agent for obesity. Drug Des. Devel. Ther., 2019, 13, 3855-3866.
[http://dx.doi.org/10.2147/DDDT.S227499] [PMID: 32009777]
[15]
Van Schaik, L.; Kettle, C.; Green, R.; Irving, H.R.; Rathner, J.A. Effects of caffeine on brown adipose tissue thermogenesis and metabolic homeostasis: A review. Front. Neurosci., 2021, 15621356
[http://dx.doi.org/10.3389/fnins.2021.621356] [PMID: 33613184]
[16]
Shen, W.; Xu, Y.; Lu, Y.H. Inhibitory effects of citrus flavonoids on starch digestion and antihyperglycemic effects in HepG2 cells. J. Agric. Food Chem., 2012, 60(38), 9609-9619.
[http://dx.doi.org/10.1021/jf3032556] [PMID: 22958058]
[17]
Al Shukor, N.; Ravallec, R.; Van Camp, J.; Raes, K.; Smagghe, G. Flavonoids stimulate cholecystokinin peptide secretion from the enteroendocrine STC-1 cells. Fitoterapia, 2016, 113, 128-131.
[http://dx.doi.org/10.1016/j.fitote.2016.07.016] [PMID: 27496247]
[18]
Wang, X.; Hasegawa, J.; Kitamura, Y.; Wang, Z.; Matsuda, A.; Shinoda, W.; Miura, N.; Kimura, K. Effects of hesperidin on the progression of hypercholesterolemia and fatty liver induced by high-cholesterol diet in rats. J. Pharmacol. Sci., 2011, 117(3), 129-138.
[http://dx.doi.org/10.1254/jphs.11097FP] [PMID: 21979313]
[19]
Ahmadi, A.; Shadboorestan, A. Oxidative stress and cancer; the role of hesperidin, a citrus natural bioflavonoid, as a cancer chemoprotective agent. Nutr. Cancer, 2016, 68(1), 29-39.
[http://dx.doi.org/10.1080/01635581.2015.1078822] [PMID: 26381129]
[20]
Hwang, M.; Kim, J.N.; Kim, B.J. Hesperidin depolarizes the pacemaker potentials through 5-HT4 receptor in murine small intestinal interstitial cells of Cajal. Anim. Cells Syst., 2020, 24(2), 84-90.
[http://dx.doi.org/10.1080/19768354.2020.1746398] [PMID: 32489687]
[21]
Al-Shboul, O. The importance of interstitial cells of cajal in the gastrointestinal tract. Saudi J. Gastroenterol., 2013, 19(1), 3-15.
[http://dx.doi.org/10.4103/1319-3767.105909] [PMID: 23319032]
[22]
Kim, B.J.; Kwon, H.E.; Kim, J.N.; Kwon, M.J.; Lee, J.R.; Kim, S.C.; Nam, J.H. The traditional medicine Bojungikki-tang increases intestinal motility. Pharmacogn. Mag., 2021, 17(5), 1.
[http://dx.doi.org/10.4103/pm.pm_507_20]
[23]
Wouters, M.M.; Farrugia, G.; Schemann, M. 5-HT receptors on interstitial cells of Cajal, smooth muscle and enteric nerves. Neurogastroenterol. Motil., 2007, 19(Suppl. 2), 5-12.
[http://dx.doi.org/10.1111/j.1365-2982.2007.00963.x] [PMID: 17620082]
[24]
Vabeiryureilai, M.; Lalrinzuali, K.; Jagetia, G.C. Chemopreventive effect of hesperidin, a citrus bioflavonoid in two stage skin carcinogenesis in Swiss albino mice. Heliyon, 2019, 5(10)e02521
[http://dx.doi.org/10.1016/j.heliyon.2019.e02521] [PMID: 31720442]
[25]
Miyagi, Y.; Om, A.S.; Chee, K.M.; Bennink, M.R. Inhibition of azoxymethane-induced colon cancer by orange juice. Nutr. Cancer, 2000, 36(2), 224-229.
[http://dx.doi.org/10.1207/S15327914NC3602_12] [PMID: 10890034]
[26]
Yang, M.; Tanaka, T.; Hirose, Y.; Deguchi, T.; Mori, H.; Kawada, Y. Chemopreventive effects of diosmin and hesperidin onN-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary-bladder carcinogenesis in male ICR mice. Int. J. Cancer, 1997, 73(5), 719-724.
[http://dx.doi.org/10.1002/(SICI)1097-0215(19971127)73:5<719:AID-IJC18>3.0.CO;2-0] [PMID: 9398052]
[27]
Salman, M.; Naseem, I. Riboflavin as adjuvant with cisplatin: Study in mouse skin cancer model. Front. Biosci., 2015, 7(2), 242-254.
[PMID: 25553377]
[28]
Murakami, A.; Kuki, W.; Takahashi, Y.; Yonei, H.; Nakamura, Y.; Ohto, Y.; Ohigashi, H.; Koshimizu, K. Auraptene, a citrus coumarin, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in ICR mouse skin, possibly through suppression of superoxide generation in leukocytes. Jpn. J. Cancer Res., 1997, 88(5), 443-452.
[http://dx.doi.org/10.1111/j.1349-7006.1997.tb00402.x] [PMID: 9247600]
[29]
Lai, C.S.; Wu, J.C.; Ho, C.T.; Pan, M.H. Disease chemopreventive effects and molecular mechanisms of hydroxylated polymethoxyflavones. Biofactors, 2015, 41(5), 301-313.
[http://dx.doi.org/10.1002/biof.1236]
[30]
Pourakbari, R.; Taher, S.M.; Mosayyebi, B.; Ayoubi-Joshaghani, M.H.; Ahmadi, H.; Aghebati-Maleki, L. Implications for glycosylated compounds and their anti-cancer effects. Int. J. Biol. Macromol., 2020, 163, 1323-1332.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.06.281] [PMID: 32622770]
[31]
Tan, S.; Dai, L.; Tan, P.; Liu, W.; Mu, Y.; Wang, J.; Huang, X.; Hou, A. Hesperidin administration suppresses the proliferation of lung cancer cells by promoting apoptosis via targeting the miR 132/ZEB2 signalling pathway. Int. J. Mol. Med., 2020, 46(6), 2069-2077.
[http://dx.doi.org/10.3892/ijmm.2020.4756] [PMID: 33125117]
[32]
Birsu, C.Z.; Unlu, M.; Kiran, B.; Sinem, B.E.; Baran, Y.; Cakmakoglu, B. Anti-proliferative, apoptotic and signal transduction effects of hesperidin in non-small cell lung cancer cells. Cell. Oncol., 2015, 38(3), 195-204.
[http://dx.doi.org/10.1007/s13402-015-0222-z] [PMID: 25860498]
[33]
Aggarwal, A.; Kumari, R.; Mehla, N. Deepali; Singh, R.P.; Bhatnagar, S.; Sharma, K.; Sharma, K.; Amit, V.; Rathi, B. Depletion of the ozone layer and its consequences: A review. Am. J. Plant Sci., 2013, 4(10), 1990-1997.
[http://dx.doi.org/10.4236/ajps.2013.410247]
[34]
Durbeej, B.; Eriksson, L.A. Reaction mechanism of thymine dimer formation in DNA induced by UV light. J. Photochem. Photobiol. Chem., 2002, 152(1-3), 95-101.
[http://dx.doi.org/10.1016/S1010-6030(02)00180-6]
[35]
Sander, C.S.; Chang, H.; Hamm, F.; Elsner, P.; Thiele, J.J. Role of oxidative stress and the antioxidant network in cutaneous carcinogenesis. Int. J. Dermatol., 2004, 43(5), 326-335.
[http://dx.doi.org/10.1111/j.1365-4632.2004.02222.x] [PMID: 15117361]
[36]
Petrova, A.; Davids, L.M.; Rautenbach, F.; Marnewick, J.L. Photoprotection by honeybush extracts, hesperidin and mangiferin against UVB-induced skin damage in SKH-1 mice. J. Photochem. Photobiol. B, 2011, 103(2), 126-139.
[http://dx.doi.org/10.1016/j.jphotobiol.2011.02.020] [PMID: 21435898]
[37]
Martinez, R.M.; Pinho-Ribeiro, F.A.; Steffen, V.S.; Caviglione, C.V.; Vignoli, J.A.; Baracat, M.M.; Georgetti, S.R.; Verri, W.A., Jr; Casagrande, R. Hesperidin methyl chalcone inhibits oxidative stress and inflammation in a mouse model of ultraviolet B irradiation-induced skin damage. J. Photochem. Photobiol. B, 2015, 148, 145-153.
[http://dx.doi.org/10.1016/j.jphotobiol.2015.03.030] [PMID: 25916506]
[38]
Bagher, Z.; Ehterami, A.; Safdel, M.H.; Khastar, H.; Semiari, H.; Asefnejad, A.; Davachi, S.M.; Mirzaii, M.; Salehi, M. Wound healing with alginate/chitosan hydrogel containing hesperidin in rat model. J. Drug Deliv. Sci. Technol., 2020, 55101379
[http://dx.doi.org/10.1016/j.jddst.2019.101379]
[39]
Rana, A.; Awasthi, A.; Kumar, D.; Singh, S.; Singh, S. Alzheimer’s disease silent killer of memory: A review on pathological mechanisms. J. Alzheimers Neurodegener. Dis., 2018, 4, 17.
[40]
Uttara, B.; Singh, A.; Zamboni, P.; Mahajan, R. Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol., 2009, 7(1), 65-74.
[http://dx.doi.org/10.2174/157015909787602823] [PMID: 19721819]
[41]
Solanki, I.; Parihar, P.; Parihar, M.S. Neurodegenerative diseases: From available treatments to prospective herbal therapy. Neurochem. Int., 2016, 95, 100-108.
[http://dx.doi.org/10.1016/j.neuint.2015.11.001] [PMID: 26550708]
[42]
Hajialyani, M.; Hosein, F.M.; Echeverría, J.; Nabavi, S.; Uriarte, E.; Sobarzo-Sánchez, E. Hesperidin as a neuroprotective agent: A review of animal and clinical evidence. Molecules, 2019, 24(3), 648.
[http://dx.doi.org/10.3390/molecules24030648] [PMID: 30759833]
[43]
Wang, D.; Liu, L.; Zhu, X.; Wu, W.; Wang, Y. Hesperidin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress in a mouse model of Alzheimer’s disease. Cell. Mol. Neurobiol., 2014, 34(8), 1209-1221.
[http://dx.doi.org/10.1007/s10571-014-0098-x] [PMID: 25135708]
[44]
Hernandez, F.; Lucas, J.J.; Avila, J. GSK3 and tau: Two convergence points in Alzheimer’s disease. J. Alzheimers Dis., 2012, 33(Suppl. 1), S141-S144.
[http://dx.doi.org/10.3233/JAD-2012-129025] [PMID: 22710914]
[45]
Kumar, H.; Lim, H.W.; More, S.V.; Kim, B.W.; Koppula, S.; Kim, I.S.; Choi, D.K. The role of free radicals in the aging brain and Parkinson’s Disease: Convergence and parallelism. Int. J. Mol. Sci., 2012, 13(8), 10478-10504.
[http://dx.doi.org/10.3390/ijms130810478] [PMID: 22949875]
[46]
Paim, S.A.C.; Martins, A.Á.C.; Petry, O.P.; Dalsin, M.; de Mello, R.C.R. Postoperative confusion in patients with Parkinson disease undergoing deep brain stimulation of the subthalamic nucleus. World Neurosurg., 2019, 125, e966-e971.
[http://dx.doi.org/10.1016/j.wneu.2019.01.216] [PMID: 30763744]
[47]
Priya, N.; Vijayalakshmi, K.; Khadira, S. Investigation on the neuroprotective effects of hesperidin on behavioural activities in 6-ohda induced parkinson model. Int. J. Pharm. Bio. Sci., 2014, 5(4), 570-577.
[48]
Mauludin, R.; Müller, R.H. Physicochemical properties of hesperidin nanocrystal. Int. J. Pharm. Pharm. Sci., 2013, 5(Suppl. 3), 954-960.
[49]
Manach, C.; Morand, C.; Gil-Izquierdo, A.; Bouteloup-Demange, C.; Rémésy, C. Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice. Eur. J. Clin. Nutr., 2003, 57(2), 235-242.
[http://dx.doi.org/10.1038/sj.ejcn.1601547] [PMID: 12571654]
[50]
Freag, M.S.; Elnaggar, Y.S.R.; Abdallah, O.Y. Development of novel polymer-stabilized diosmin nanosuspensions: In vitro appraisal and ex vivo permeation. Int. J. Pharm., 2013, 454(1), 462-471.
[http://dx.doi.org/10.1016/j.ijpharm.2013.06.039] [PMID: 23830765]
[51]
Dey, Y.N.; Kumar, D.; Wanjari, M.; Lomash, V. Acute and repeated dose oral toxicity studies of Amorphophallus paeoniifolius tuber in mice. J. Pharm. Pharmacogn. Res., 2017, 5, 55-68.
[52]
Dey, Y.; Mahor, S.; Kumar, D.; Wanjari, M.; Gaidhani, S.; Jadhav, A. Gastrokinetic activity of Amorphophallus paeoniifolius tuber in rats. J. Intercult. Ethnopharmacol., 2016, 5(1), 36-42.
[http://dx.doi.org/10.5455/jice.20151211063819] [PMID: 27069720]
[53]
Dey, Y.N.; Sharma, G.; Wanjari, M.M.; Kumar, D.; Lomash, V.; Jadhav, A.D. Beneficial effect of Amorphophallus paeoniifolius tuber on experimental ulcerative colitis in rats. Pharm. Biol., 2017, 55(1), 53-62.
[http://dx.doi.org/10.1080/13880209.2016.1226904] [PMID: 27600166]
[54]
Dey, Y.N.; Wanjari, M.M.; Srivastava, B.; Kumar, D.; Sharma, D.; Sharma, J.; Gaidhani, S. Beneficial effect of standardized extracts of Amorphophallus paeoniifolius tuber and its active constituents on experimental constipation in rats. Heliyon, 2020, 6(5)e04023
[http://dx.doi.org/10.1016/j.heliyon.2020.e04023] [PMID: 32509986]
[55]
Dey, Y.N.; Wanjari, M.M.; Kumar, D.; Lomash, V.; Jadhav, A.D. Curative effect of Amorphophallus paeoniifolius tuber on experimental hemorrhoids in rats. J. Ethnopharmacol., 2016, 192, 183-191.
[http://dx.doi.org/10.1016/j.jep.2016.07.042] [PMID: 27426509]
[56]
Dey, Y.N.; Mahor, S.; Sharma, D.; Wanjari, M.M.; Kumar, D.; Sharma, J. Possible role of serotonin in the gastrokinetic activity of Amorphophallus paeoniifolius tuber. Phytomedicine Plus, 2022, 2(2)100275
[http://dx.doi.org/10.1016/j.phyplu.2022.100275]
[57]
Uesawa, Y.; Mohri, K. Hesperidin in orange juice reduces the absorption of celiprolol in rats. Biopharm. Drug Dispos., 2008, 29(3), 185-188.
[http://dx.doi.org/10.1002/bdd.603] [PMID: 18344215]
[58]
Cho, Y.A.; Choi, D.H.; Choi, J.S. Effect of hesperidin on the oral pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats. J. Pharm. Pharmacol., 2010, 61(6), 825-829.
[http://dx.doi.org/10.1211/jpp.61.06.0017] [PMID: 19505375]
[59]
Piao, Y.J.; Choi, J.S. Enhanced bioavailability of verapamil after oral administration with hesperidin in rats. Arch. Pharm. Res., 2008, 31(4), 518-522.
[http://dx.doi.org/10.1007/s12272-001-1187-4] [PMID: 18449511]
[60]
Aggarwal, V.; Tuli, H.S.; Thakral, F.; Singhal, P.; Aggarwal, D.; Srivastava, S.; Pandey, A.; Sak, K.; Varol, M.; Khan, M.A.; Sethi, G. Molecular mechanisms of action of hesperidin in cancer: Recent trends and advancements. Exp. Biol. Med. , 2020, 245(5), 486-497.
[http://dx.doi.org/10.1177/1535370220903671] [PMID: 32050794]
[61]
Kuntić V.; Filipović I.; Vujić Z. Effects of rutin and hesperidin and their Al(III) and Cu(II) complexes on in vitro plasma coagulation assays. Molecules, 2011, 16(2), 1378-1388.
[http://dx.doi.org/10.3390/molecules16021378] [PMID: 21301410]
[62]
Fernández, S.P.; Wasowski, C.; Paladini, A.C.; Marder, M. Synergistic interaction between hesperidin, a natural flavonoid, and diazepam. Eur. J. Pharmacol., 2005, 512(2-3), 189-198.
[http://dx.doi.org/10.1016/j.ejphar.2005.02.039] [PMID: 15840404]

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