Generic placeholder image

Central Nervous System Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5249
ISSN (Online): 1875-6166

Review Article

Therapeutic Potential and Clinical Evidence of Hesperidin as Neuroprotective Agent

Author(s): Shivanki Joshi, Ashwani K. Dhingra*, Bhawna Chopra, Kumar Guarve and Deepak Bhateja

Volume 22, Issue 1, 2022

Published on: 23 May, 2022

Page: [5 - 14] Pages: 10

DOI: 10.2174/1871524922666220404164405

Price: $65

Abstract

Background: Neuroprotection is preserving neural function in various neurodegenerative diseases like Alzheimer’s, Huntington’s, Parkinson’s, and multiple sclerosis. Hesperidin, a flavanone glycoside in citrus fruits such as sweet oranges and lemons, possesses many biological effects, including neuroprotection.

Objective: The study aims to explore the neuropharmacological mechanisms and therapeutic potential of hesperidin in the management of neurodegenerative disorders.

Methods: It emphasizes comparative and clinical trial studies with a number of targets reviewed from the data available on PubMed, Science Direct, Clinicaltrails.gov, and from many reputed foundations.

Results: Escalating clinical evidence has established the inhibitory effect of hesperidin in the management of neurodegenerative disorders. Neuroprotective potential of hesperidin is characterized by endogenous antioxidant defence functions, improvement of neural growth factors, antineuroinflammatory activity, and apoptotic pathways.

Conclusion: The present study highlights the beneficial neuropharmacological potential of hesperidin, including anticonvulsant, antidepressant, antioxidant, anti-inflammatory, memory, and locomotor enhancing activities.

Keywords: Hesperidin, neuroprotection, Alzheimer’s, Huntington’s, Parkinson’s, clinical trials.

Graphical Abstract
[1]
Gao, H.M.; Hong, J.S. Why neurodegenerative diseases are progressive: Uncontrolled inflammation drives disease progression. Trends Immunol., 2008, 29(8), 357-365.
[http://dx.doi.org/10.1016/j.it.2008.05.002] [PMID: 18599350]
[2]
Uttara, B.; Singh, A.V.; Zamboni, P.; Mahajan, R.T. Oxidative stress and neurodegenerative diseases: A review of upstream and down-stream antioxidant therapeutic options. Curr. Neuropharmacol., 2009, 7(1), 65-74.
[http://dx.doi.org/10.2174/157015909787602823] [PMID: 19721819]
[3]
Dhingra, A.K.; Rathi, V.; Chopra, B. Resveratrol. Naturally Occurring Chemicals against Alzheimer’s Disease; Academic Press Inc., 2021, Vol. 1, pp. 33-42.
[http://dx.doi.org/10.1016/B978-0-12-819212-2.00037-2]
[4]
Kovacs, G.G. Concepts and classification of neurodegenerative diseases. Handb. Clin. Neurol., 2017, 145, 301-307.
[http://dx.doi.org/10.1016/B978-0-12-802395-2.00021-3] [PMID: 28987178]
[5]
Lin, M.T.; Beal, M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 2006, 443(7113), 787-795.
[http://dx.doi.org/10.1038/nature05292] [PMID: 17051205]
[6]
Ross, C.A.; Poirier, M.A. Protein aggregation and neurodegenerative disease. Nat. Med., 2004, 10(Suppl.), S10-S17.
[http://dx.doi.org/10.1038/nm1066] [PMID: 15272267]
[7]
Rathi, V.; Dhingra, A.K.; Chopra, B. Withania somnifera. Naturally Occurring Chemicals against Alzheimer’s Disease; Academic Press Inc., 2021, Vol. 1, pp. 401-404.
[http://dx.doi.org/10.1016/B978-0-12-819212-2.00034-7]
[8]
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]
[9]
Jellinger, K.A. Cell death mechanisms in neurodegeneration. J. Cell. Mol. Med., 2001, 5(1), 1-17.
[http://dx.doi.org/10.1111/j.1582-4934.2001.tb00134.x] [PMID: 12067447]
[10]
Parihar, M.S.; Parihar, A.; Fujita, M.; Hashimoto, M.; Ghafourifar, P. Mitochondrial association of alpha-synuclein causes oxidative stress. Cell. Mol. Life Sci., 2008, 65(7-8), 1272-1284.
[http://dx.doi.org/10.1007/s00018-008-7589-1] [PMID: 18322646]
[11]
Saini, D.; Dhingra, A.K.; Chopra, B.; Parle, M. Evaluation of Nootropic activity of Trigonella foenum leaves in mice. Int. J. Pharm. Pharm. Sci., 2012, 4(4), 136-143.
[12]
Saini, D.; Dhingra, A.K.; Chopra, B.; Parle, M. Psychopharmacological investigation of the nootropic potential of trigonella foenum linn in mice. Asian J. Pharm. Clin. Res., 2011, 4(4), 76-84.
[13]
Dhingra, A.K.; Chopra, B. Inflammation as a therapeutic target for various deadly disorders: A review. Curr. Drug Targets, 2020, 21(6), 582-588.
[http://dx.doi.org/10.2174/1389450120666191204154115] [PMID: 31801453]
[14]
Gilgun-Sherki, Y.; Melamed, E.; Offen, D. Oxidative stress induced-neurodegenerative diseases: The need for antioxidants that penetrate the blood brain barrier. Neuropharmacology, 2001, 40(8), 959-975.
[http://dx.doi.org/10.1016/S0028-3908(01)00019-3] [PMID: 11406187]
[15]
Dhingra, A.K.; Chopra, B.; Dass, R.; Mittal, S.K. An update on anti-inflammatory compounds: A review. Antiinflamm. Antiallergy Agents Med. Chem., 2015, 14(2), 81-97.
[http://dx.doi.org/10.2174/1871523014666150514102027] [PMID: 25973652]
[16]
Dhingra, A.K.; Chopra, B.; Dass, R.; Mittal, S.K. A review of medicinal plants possessing antidepressant potential. Indian Drugs, 2016, 53(6), 5-17.
[http://dx.doi.org/10.53879/id.53.06.10436]
[17]
Chopra, B.; Dhingra, A.K. Natural products: A lead for drug discovery and development. Phytother. Res., 2021. (Online ahead of print)
[http://dx.doi.org/10.1002/ptr.7099]
[18]
Yoo, S.; Kim, K.; Nam, H.; Lee, D. Discovering health benefits of phytochemicals with integrated analysis of the molecular network, chemical properties and ethnopharmacological evidence. Nutrients, 2018, 10(8), 1042.
[http://dx.doi.org/10.3390/nu10081042] [PMID: 30096807]
[19]
Johnson, I.T. Phytochemicals and cancer. Proc. Nutr. Soc., 2007, 66(2), 207-215.
[http://dx.doi.org/10.1017/S0029665107005459] [PMID: 17466103]
[20]
Cinzia, F.; Francesci, F.; Maneula, B. Beneficial role of phytochemicals on oxidative stress and age related disease. BioMed Res. Int., 2019, 2019, 1-16.
[21]
Dhingra, A.K.; Chopra, B.; Bonthagarala, B. Natural anti-inflammatory agents: Recent progress and future perspectives. Ann. Pharmacol. Pharm., 2018, 3(4), 1158-1168.
[22]
Lee, Y.S.X.; Huh, J.Y.; Nam, S.H.; Moon, S.K.; Lee, S.B. Enzymatic bioconversion of citrus hesperidin by Aspergillus sojae naringinase: Enhanced solubility of hesperetin-7-O-glucoside with vitro inhibition of human intestinal maltase, HMG-CoA reductase, and growth of Helicobacter pylori. Food Chem., 2012, 135(4), 2253-2259.
[http://dx.doi.org/10.1016/j.foodchem.2012.07.007] [PMID: 22980799]
[23]
Yu, W.; Xie, X.; Yu, Z.; Jin, Q.; Wu, H. Mechanism of hesperidin-induced apoptosis in human gastric cancer AGS cells. Trop. J. Pharm. Res., 2019, 8(11), 2363-2369.
[24]
Mosqueda-Solís, A.; Sánchez, J.; Reynés, B.; Palou, M.; Portillo, M.P.; Palou, A.; Picó, C. Hesperidin and capsaicin, but not the combina-tion, prevent hepatic steatosis and other metabolic syndrome-related alterations in western diet-fed rats. Sci. Rep., 2018, 8(1), 15100.
[http://dx.doi.org/10.1038/s41598-018-32875-4] [PMID: 30305645]
[25]
Afzal, S.M.; Vafa, A.; Rashid, S.; Barnwal, P.; Shahid, A.; Shree, A.; Islam, J.; Ali, N.; Sultana, S. Protective effect of hesperidin against N,N′-dimethylhydrazine induced oxidative stress, inflammation, and apoptotic response in the colon of Wistar rats. Environ. Toxicol., 2020, 1-12.
[PMID: 33289288]
[26]
Li, C.; Schluesener, H. Health- promoting effect of citrus flavanones hesperidin. Crit. Rev. Food Sci. Nutr., 2017, 57, 6143-6631.
[http://dx.doi.org/10.1080/10408398.2014.906382]
[27]
Prasatthong, P.; Meephat, S.; Rattanakanokchai, S.; Bunbupha, S.; Prachaney, P.; Maneesai, P.; Pakdeechote, P. Hesperidin ameliorates signs of the metabolic syndrome and cardiac dysfunction via IRS/Akt/GLUT4 signaling pathway in a rat model of diet-induced metabolic syndrome. Eur. J. Nutr., 2020, 1-16.
[PMID: 32462317]
[28]
Gosslau, A.; Zachariah, E.; Li, S.; Ho, C.T. Effects of a favonoid-enriched orange peel extract against type 2 diabetes in the obese ZDF rat model. Food Sci. Hum. Wellness, 2018, 7(4), 244-251.
[http://dx.doi.org/10.1016/j.fshw.2018.10.001]
[29]
Mayneris-perxachs, J.; Alcaide-Hidalgo, J.; la-Hera, E.; Del Bas, J.; Arola, L.; Caimari, A. Supplementation with biscuits enriched with hesperidin and naringenin is associated with an improvement of the metabolic syndrome induced by a cafeteria diet in rats. J. Funct. Foods, 2019, 61, 103504.
[http://dx.doi.org/10.1016/j.jff.2019.103504]
[30]
Man, M.Q.; Yang, B.; Elias, P.M. Benefits of hesperidin for cutaneous functions. Evid. Based Complement. Alternat. Med., 2019, 2019, 2676307.
[http://dx.doi.org/10.1155/2019/2676307] [PMID: 31061668]
[31]
Garg, A.; Garg, S.; Zaneveld, L.J.; Singla, A.K. Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. Phytother. Res., 2001, 15(8), 655-669.
[http://dx.doi.org/10.1002/ptr.1074] [PMID: 11746857]
[32]
Barthe, G.A.; Jourdan, P.S.; McIntosh, C.A.; Mansell, R.L. Radioimmunoassay for the quantitative determination of hesperidin and analy-sis of its distribution in Citrus sinensis. Phytochemistry, 1998, 27(1), 249-254.
[http://dx.doi.org/10.1016/0031-9422(88)80625-3]
[33]
Inoue, T.; Tsubaki, S.; Ogawa, K.; Onishi, K.; Azuma, J.I. Isolation of hesperidin from peels of thinned Citrus unshiu fruits by micro-wave-assisted extraction. Food Chem., 2010, 123(2), 542-547.
[http://dx.doi.org/10.1016/j.foodchem.2010.04.051]
[34]
Rouseff, R.L.; Martin, S.F.; Youtsey, C.O. Quantitative survey of narirutin, naringin, hesperidin, and neohesperidin in citrus. J. Agric. Food Chem., 1987, 35(6), 1027-1030.
[http://dx.doi.org/10.1021/jf00078a040]
[35]
Lu, Y.; Zhang, C.; Bucheli, P.; Wei, D. Citrus flavonoids in fruit and traditional Chinese medicinal food ingredients in China. Plant Foods Hum. Nutr., 2006, 61(2), 57-65.
[http://dx.doi.org/10.1007/s11130-006-0014-8] [PMID: 16816988]
[36]
Yoo, K.M.; Lee, K.W.; Park, J.B.; Lee, H.J.; Hwang, I.K. Variation in major antioxidants and total antioxidant activity of Yuzu (Citrus junos Sieb ex Tanaka) during maturation and between cultivars. J. Agric. Food Chem., 2004, 52(19), 5907-5913.
[http://dx.doi.org/10.1021/jf0498158] [PMID: 15366841]
[37]
Bhalla, N.; Dakwale, R. Chemotaxonomy of indigofera linn. J. Indian Bot. Soc., 1978, 57, 180-185.
[38]
Kokkalou, E. Kapetanidis, flavonoids of the aerial parts of acinossuaveolens. Pharm. Acta Helv., 1998, 636, 170-173.
[39]
Pawłowska, L. Flavonoids in the leaves of polish species of the genus Betula L. L The flavonoids of B. pendula Roth. and B. obscura Kot. leaves. Acta Soc. Bot. Pol., 1980, 49(3), 281-296.
[http://dx.doi.org/10.5586/asbp.1980.025]
[40]
Negi, J.; Bisht, V.; Bhandari, A.; Singh, P.; Sundriyal, R. Chemical constituents and biological activities of the genus Zanthoxylum: A re-view. Afr. J. Pure Appl. Chem, 2011, 5(12), 412-416.
[41]
Zhao, W.; Qin, G.; Xu, R.; Li, X.; Liu, J.; Wang, Y.; Feng, M. Constituents from the roots of Acanthopanax setchuenensis. Fitoterapia, 1999, 70(5), 529-531.
[http://dx.doi.org/10.1016/S0367-326X(99)00078-7]
[42]
Roohbakhsh, A.; Parhiz, H.; Soltani, F.; Rezaee, R.; Iranshahi, M. Neuropharmacological properties and pharmacokinetics of the citrus flavonoids hesperidin and hesperetin--a mini-review. Life Sci., 2014, 113(1-2), 1-6.
[http://dx.doi.org/10.1016/j.lfs.2014.07.029] [PMID: 25109791]
[43]
Jin, M.J.; Kim, U.; Kim, I.S.; Kim, Y.; Kim, D.H.; Han, S.B.; Kim, D.H.; Kwon, O.S.; Yoo, H.H. Effects of gut microflora on pharmacoki-netics of hesperidin: A study on non-antibiotic and pseudo-germ-free rats. J. Toxicol. Environ. Health A, 2010, 73(21-22), 1441-1450.
[http://dx.doi.org/10.1080/15287394.2010.511549] [PMID: 20954071]
[44]
Pereira-Caro, G.; Polyviou, T.; Ludwig, I.A.; Nastase, A.M.; Moreno-Rojas, J.M.; Garcia, A.L.; Malkova, D.; Crozier, A. Bioavailability of orange juice (poly)phenols: The impact of short-term cessation of training by male endurance athletes. Am. J. Clin. Nutr., 2017, 106(3), 791-800.
[http://dx.doi.org/10.3945/ajcn.116.149898] [PMID: 28747329]
[45]
Mas-Capdevila, A.; Teichenne, J.; Domenech-Coca, C.; Caimari, A.; Del Bas, J.M.; Escoté, X.; Crescenti, A. Effect of hesperidin on cardi-ovascular 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]
[46]
Justin Thenmozhi, A.; Raja, T.R.W.; Janakiraman, U.; Manivasagam, T. Neuroprotective effect of hesperidin on aluminium chloride in-duced Alzheimer’s disease in Wistar rats. Neurochem. Res., 2015, 40(4), 767-776.
[http://dx.doi.org/10.1007/s11064-015-1525-1] [PMID: 25630717]
[47]
Yurtal, Z.; Altug, M.E.; Unsaldi, E.; Secinti, I.E.; Kucukgul, A. Investigation of neuroprotective and therapeutic effects of hesperidin in experimental spinal cord injury. Turk Neurosurg., 2020, 30(6), 899-906.
[http://dx.doi.org/10.5137/1019-5149.JTN.29611-20.2] [PMID: 33216334]
[48]
Guzmán-Gutiérrez, S.L.; Navarrete, A. Pharmacological exploration of the sedative mechanism of hesperidin identified as the active prin-ciple of Citrus sinensis flowers. Planta Med., 2009, 75(4), 295-301.
[http://dx.doi.org/10.1055/s-0029-1185306] [PMID: 19219759]
[49]
Welbat, J.U.; Naewla, S.; Pannangrong, W.; Sirichoat, A.; Aranarochana, A.; Wigmore, P. Neuroprotective effects of hesperidin against methotrexate-induced changes in neurogenesis and oxidative stress in the adult rat. Biochem. Pharmacol., 2020, 178, 114083.
[http://dx.doi.org/10.1016/j.bcp.2020.114083] [PMID: 32522593]
[50]
Mottay, D.; Neergheen-Bhujun, V.S. Anticholinesterase and antioxidant effects of traditional herbal medicines used in the management of neurodegenerative diseases in mauritius. Arch. Med. Biomed. Res., 2015, 2, 114-130.
[http://dx.doi.org/10.4314/ambr.v2i4.2]
[51]
Kivrak, I.; Duru, M.E.; Ozturk, M.; Mercan, N.; Harmandar, M.; Topcu, G. Antioxidant, anticholinesterase and antimicrobial constituents from the essential oil and ethanol extract of Salvia potentillifolia. Food Chem., 2009, 116, 470-479.
[http://dx.doi.org/10.1016/j.foodchem.2009.02.069]
[52]
Antunes, M.S.; Cattelan Souza, L.; Ladd, F.V.L.; Ladd, A.A.B.L.; Moreira, A.L.; Bortolotto, V.C.; Silva, M.R.P.; Araújo, S.M.; Prigol, M.; Nogueira, C.W.; Boeira, S.P. Hesperidin ameliorates anxiety-depressive-like behavior in 6-OHDA model of parkinson’s disease by regu-lating striatal cytokine and neurotrophic factors levels and dopaminergic innervation loss in the striatum of mice. Mol. Neurobiol., 2020, 57(7), 3027-3041.
[http://dx.doi.org/10.1007/s12035-020-01940-3] [PMID: 32458386]
[53]
Antunes, M.S.; Goes, A.T.R.; Boeira, S.P.; Prigol, M.; Jesse, C.R. Protective effect of hesperidin in a model of Parkinson’s disease induced by 6-hydroxydopamine in aged mice. Nutrition, 2014, 30(11-12), 1415-1422.
[http://dx.doi.org/10.1016/j.nut.2014.03.024] [PMID: 25280422]
[54]
Souza, L.C.; de Gomes, M.G.; Goes, A.T.; Del Fabbro, L.; Filho, C.B.; Boeira, S.P.; Jesse, C.R. Evidence for the involvement of the sero-tonergic 5-HT(1A) receptors in the antidepressant-like effect caused by hesperidin in mice. Neuro-Psychoph., 2013, 40, 103-109.
[http://dx.doi.org/10.1016/j.pnpbp.2012.09.003] [PMID: 22996046]
[55]
Salem, H.R.A.; El-Raouf, A.; Saleh, E.M.; Shalaby, K.A. Influence of hesperidin combined with Sinemeton genetical and biochemical abnormalities in rats suffering from Parkinson’s disease. Life Sci. J., 2012, 9, 930-945.
[56]
Nagappan, P.; Krishnamurthy, V.; Sereen, K. Investigation of the neuroprotective effect of hesperidin on behavioural activities in 6-OHDA induced Parkinson model. Int. J. Pharm. Biol. Sci., 2014, 5(4), 570-577.
[57]
Tamilselvam, K.; Nataraj, J.; Janakiraman, U.; Manivasagam, T.; Essa, M.M. Antioxidant and anti-inflammatory potential of hesperidin against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced experimental Parkinson’s disease in mice. Int. J. Nutr. Pharmacol. Neurol. Dis., 2013, 3(3), 294-302.
[http://dx.doi.org/10.4103/2231-0738.114875]
[58]
Nagappan, P.; Krishnamurthy, V. Anti-parkinson effect of hesperidin in combination with L-DOPA on 6-OHDA induced parkinsonism in wistar rats-a neurochemical, histopathological and immunohistochemical analysis. Int. J. Pharm. Tech. Res., 2016, 9, 266-273.
[59]
Santos, G.; Giraldez-Alvarez, L.D.; Ávila-Rodriguez, M.; Capani, F.; Galembeck, E.; Neto, A.G.; Barreto, G.E.; Andrade, B. SUR1 receptor interaction with hesperidin and linarin predicts possible mechanisms of action of valeriana officinalis in parkinson. Front. Aging Neurosci., 2016, 8, 97.
[http://dx.doi.org/10.3389/fnagi.2016.00097] [PMID: 27199743]
[60]
Jiménez-Aliaga, K.; Bermejo-Bescós, P.; Benedí, J.; Martín-Aragón, S. Quercetin and rutin exhibit antiamyloidogenic and fibril-disaggregating effects vitro and potent antioxidant activity in APPswe cells. Life Sci., 2011, 89(25-26), 939-945.
[http://dx.doi.org/10.1016/j.lfs.2011.09.023] [PMID: 22008478]
[61]
Qin, X.Y.; Cheng, Y.; Yu, L.C. Potential protection of green tea polyphenols against intracellular amyloid beta-induced toxicity on primary cultured prefrontal cortical neurons of rats. Neurosci. Lett., 2012, 513(2), 170-173.
[http://dx.doi.org/10.1016/j.neulet.2012.02.029] [PMID: 22381400]
[62]
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]
[63]
Badalzadeh, R.; Mohammadi, M.; Yousefi, B.; Farajnia, S.; Najafi, M.; Mohammadi, S. Involvement of glycogen synthase kinase-3β and oxidation status in the loss of cardio protection by postconditioning in chronic diabetic male rats. Adv. Pharm. Bull., 2015, 5(3), 321-327.
[http://dx.doi.org/10.15171/apb.2015.045] [PMID: 26504753]
[64]
DaRocha-Souto, B.; Coma, M.; Pérez-Nievas, B.G.; Scotton, T.C.; Siao, M.; Sánchez-Ferrer, P.; Hashimoto, T.; Fan, Z.; Hudry, E.; Bar-roeta, I.; Serenó, L.; Rodríguez, M.; Sánchez, M.B.; Hyman, B.T.; Gómez-Isla, T. Activation of glycogen synthase kinase-3 beta mediates β-amyloid induced neuritic damage in Alzheimer’s disease. Neurobiol. Dis., 2012, 45(1), 425-437.
[http://dx.doi.org/10.1016/j.nbd.2011.09.002] [PMID: 21945540]
[65]
Justin Thenmozhi, A.; William Raja, T.R.; Manivasagam, T.; Janakiraman, U.; Essa, M.M. Hesperidin ameliorates cognitive dysfunction, oxidative stress and apoptosis against aluminium chloride induced rat model of Alzheimer’s disease. Nutr. Neurosci., 2017, 20(6), 360-368.
[http://dx.doi.org/10.1080/1028415X.2016.1144846] [PMID: 26878879]
[66]
Li, C.; Zug, C.; Qu, H.; Schluesener, H.; Zhang, Z. Hesperidin ameliorates behavioral impairments and neuropathology of transgenic APP/PS1 mice. Behav. Brain Res., 2015, 281(Suppl. C), 32-42.
[http://dx.doi.org/10.1016/j.bbr.2014.12.012] [PMID: 25510196]
[67]
Ghorbani, A.; Nazari, M.; Jeddi-Tehrani, M.; Zand, H. The citrus flavonoid hesperidin induces p53 and inhibits NF-κB activation in order to trigger apoptosis in NALM-6 cells: Involvement of PPARγ-dependent mechanism. Eur. J. Nutr., 2012, 51(1), 39-46.
[http://dx.doi.org/10.1007/s00394-011-0187-2] [PMID: 21445621]
[68]
Gray, C.W.; Patel, A.J. Regulation of β-amyloid precursor protein isoform mRNAs by transforming growth factor-β 1 and interleukin-1 β in astrocytes. Brain Res. Mol. Brain Res., 1993, 19(3), 251-256.
[http://dx.doi.org/10.1016/0169-328X(93)90037-P] [PMID: 8412571]
[69]
Javed, H.; Vaibhav, K.; Ahmed, M.E.; Khan, A.; Tabassum, R.; Islam, F.; Safhi, M.M.; Islam, F. Effect of hesperidin on neurobehavioral, neuroinflammation, oxidative stress and lipid alteration in intracerebroventricular streptozotocin induced cognitive impairment in mice. J. Neurol. Sci., 2015, 348(1-2), 51-59.
[http://dx.doi.org/10.1016/j.jns.2014.10.044] [PMID: 25434716]
[70]
Hemanth Kumar, B.; Dinesh Kumar, B.; Diwan, P.V. Hesperidin, a citrus flavonoid, protects against l-methionine-induced hyperhomocys-teinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats. Pharm. Biol., 2017, 55(1), 146-155.
[http://dx.doi.org/10.1080/13880209.2016.1231695] [PMID: 27677544]
[71]
Kumar, B.H.; Kumar, B.D.; Diwan, P.V. Protective effects of natural dietary antioxidants fisetin and hesperidin on chronic mild hyper homocysteinemia-induced vascular dementia in wistar rats. J. Neurol. Sci., 2017, 381, 319.
[http://dx.doi.org/10.1016/j.jns.2017.08.905]
[72]
Habibyar, A.F.; Sharma, N.; Khurana, N. PASS assisted prediction and pharmacological evaluation of hesperidin against scopolamine induced amnesia in mice. Eur. J. Pharmacol., 2016, 789(Suppl. C), 385-394.
[http://dx.doi.org/10.1016/j.ejphar.2016.07.013] [PMID: 27397428]
[73]
Rosas, H.D.; Lee, S.Y.; Bender, A.C.; Zaleta, A.K.; Vangel, M.; Yu, P.; Fischl, B.; Pappu, V.; Onorato, C.; Cha, J.H.; Salat, D.H.; Hersch, S.M. Altered white matter microstructure in the corpus callosum in Huntington’s disease: Implications for cortical “disconnection”. Neuroimage, 2010, 49(4), 2995-3004.
[http://dx.doi.org/10.1016/j.neuroimage.2009.10.015] [PMID: 19850138]
[74]
Rosas, H.D.; Liu, A.K.; Hersch, S.; Glessner, M.; Ferrante, R.J.; Salat, D.H.; van der Kouwe, A.; Jenkins, B.G.; Dale, A.M.; Fischl, B. Re-gional and progressive thinning of the cortical ribbon in Huntington’s disease. Neurology, 2002, 58(5), 695-701.
[http://dx.doi.org/10.1212/WNL.58.5.695] [PMID: 11889230]
[75]
Menze, E.T.; Tadros, M.G.; Abdel-Tawab, A.M.; Khalifa, A.E. Potential neuroprotective effects of hesperidin on 3-nitropropionic acid-induced neurotoxicity in rats. Neurotoxicology, 2012, 33(5), 1265-1275.
[http://dx.doi.org/10.1016/j.neuro.2012.07.007] [PMID: 22850463]
[76]
Kumar, P.; Kumar, A. 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., 2010, 206(1), 38-46.
[http://dx.doi.org/10.1016/j.bbr.2009.08.028] [PMID: 19716383]
[77]
Filho, C.B.; Del Fabbro, L.; de Gomes, M.G.; Goes, A.T.R.; Souza, L.C.; Boeira, S.P.; Jesse, C.R. Kappa-opioid receptors mediate the anti-depressant-like activity of hesperidin in the mouse forced swimming test. Eur. J. Pharmacol., 2013, 698(1-3), 286-291.
[http://dx.doi.org/10.1016/j.ejphar.2012.11.003] [PMID: 23178563]
[78]
Coull, J.A.M.; Beggs, S.; Boudreau, D.; Boivin, D.; Tsuda, M.; Inoue, K.; Gravel, C.; Salter, M.W.; De Koninck, Y. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature, 2005, 438(7070), 1017-1021.
[http://dx.doi.org/10.1038/nature04223] [PMID: 16355225]
[79]
Kumar, A.; Chaudhary, T.; Mishra, J. Minocycline modulates neuroprotective effect of hesperidin against quinolinic acid induced Hun-tington’s disease like symptoms in rats: Behavioral, biochemical, cellular and histological evidences. Eur. J. Pharmacol., 2013, 720(1-3), 16-28.
[http://dx.doi.org/10.1016/j.ejphar.2013.10.057] [PMID: 24211676]
[80]
Ontaneda, D.; Thompson, A.J.; Fox, R.J.; Cohen, J.A. Progressive multiple sclerosis: Prospects for disease therapy, repair, and restoration of function. Lancet, 2017, 389(10076), 1357-1366.
[http://dx.doi.org/10.1016/S0140-6736(16)31320-4] [PMID: 27889191]
[81]
Farzaei, M.H.; Shahpiri, Z.; Bahramsoltani, R.; Nia, M.M.; Najafi, F.; Rahimi, R. Efficacy and tolerability of phytomedicines in multiple sclerosis patients: A review. CNS Drugs, 2017, 31(10), 867-889.
[http://dx.doi.org/10.1007/s40263-017-0466-4] [PMID: 28948486]
[82]
Minagar, A.; Shapshak, P.; Alexander, J.S. Dementia and Multiple Sclerosis: Role of Microglia and Astrocytes; Role Glia; Neurotox, 2004, p. 263.
[83]
Muili, K.A.; Gopalakrishnan, S.; Meyer, S.L.; Eells, J.T.; Lyons, J-A. Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by photobiomodulation induced by 670 nm light. PLoS One, 2012, 7(1), e30655.
[http://dx.doi.org/10.1371/journal.pone.0030655] [PMID: 22292010]
[84]
Haghmorad, D.; Mahmoudi, M.B.; Salehipour, Z.; Jalayer, Z.; Momtazi Brojeni, A.A.; Rastin, M.; Kokhaei, P.; Mahmoudi, M. Hesperidin ameliorates immunological outcome and reduces neuroinflammation in the mouse model of multiple sclerosis. J. Neuroimmunol., 2017, 302, 23-33.
[http://dx.doi.org/10.1016/j.jneuroim.2016.11.009] [PMID: 27912911]
[85]
Ciftci, O.; Ozcan, C.; Kamisli, O.; Cetin, A.; Basak, N.; Aytac, B. Hesperidin, a citrus flavonoid, has the ameliorative effects against exper-imental autoimmune encephalomyelitis (EAE) in a C57BL/J6 mouse model. Neurochem. Res., 2015, 40(6), 1111-1120.
[http://dx.doi.org/10.1007/s11064-015-1571-8] [PMID: 25859982]
[86]
Craft, S. Alzheimer disease: Insulin resistance and AD--extending the translational path. Nat. Rev. Neurol., 2012, 8(7), 360-362.
[http://dx.doi.org/10.1038/nrneurol.2012.112] [PMID: 22710630]
[87]
Takeda, S.; Sato, N.; Uchio-Yamada, K.; Sawada, K.; Kunieda, T.; Takeuchi, D.; Kurinami, H.; Shinohara, M.; Rakugi, H.; Morishita, R. Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with dia-betes. Proc. Natl. Acad. Sci. USA, 2010, 107(15), 7036-7041.
[http://dx.doi.org/10.1073/pnas.1000645107] [PMID: 20231468]
[88]
Hsu, F.L.; Liu, I.M.; Kuo, D.H.; Chen, W.C.; Su, H.C.; Cheng, J.T. Antihyperglycemic effect of puerarin in streptozotocin-induced diabetic rats. J. Nat. Prod., 2003, 66(6), 788-792.
[http://dx.doi.org/10.1021/np0203887] [PMID: 12828463]
[89]
Ibrahim, S.S. Protective effect of hesperidin, a citrus bioflavonoid, on diabetes-induced brain damage in rats. J. Appl. Sci. Res., 2008, 4, 84-95.
[90]
Khowal, S.; Mustufa, M.M.; Chaudhary, N.K.; Naqvi, S.H.; Parvez, S.; Jain, S.K.; Wajid, S. Assessment of the therapeutic potential of hesperidin and proteomic resolution of diabetes-mediated neuronal fluctuations expediting Alzheimer’s disease. RSC Advances, 2015, 5, 46965-46980.
[http://dx.doi.org/10.1039/C5RA01977J]
[91]
Ashafaq, M.; Varshney, L.; Khan, M.H.A.; Salman, M.; Naseem, M.; Wajid, S.; Parvez, S. Neuromodulatory effects of hesperidin in miti-gating oxidative stress in streptozotocin induced diabetes. BioMed Res. Int., 2014, 2014, 249031.
[http://dx.doi.org/10.1155/2014/249031] [PMID: 25050332]
[92]
Visnagri, A.; Kandhare, A.D.; Chakravarty, S.; Ghosh, P.; Bodhankar, S.L. Hesperidin, a flavanoglycone attenuates experimental diabetic neuropathy via modulation of cellular and biochemical marker to improve nerve functions. Pharm. Biol., 2014, 52(7), 814-828.
[http://dx.doi.org/10.3109/13880209.2013.870584] [PMID: 24559476]
[93]
Miranda, H.F.; Sierralta, F.; Jorquera, V.; Poblete, P.; Prieto, J.C.; Noriega, V. Antinociceptive interaction of gabapentin with minocycline in murine diabetic neuropathy. Inflammo. Pharmacol., 2017, 25(1), 91-97.
[http://dx.doi.org/10.1007/s10787-017-0308-5] [PMID: 28155118]
[94]
Kakadiya, J.; Patel, D.; Shah, N. Effect of hesperidin on renal complication in experimentally induced renal damage in diabetic Sprague dawley rats. J. Ecobiotech, 2010, 2, 45-50.
[95]
Gustafson-Vickers, S.L.; Lu, V.B.; Lai, A.Y.; Todd, K.G.; Ballanyi, K.; Smith, P.A. Long-term actions of interleukin-1β on delay and tonic firing neurons in rat superficial dorsal horn and their relevance to central sensitization. Mol. Pain, 2008, 4(63), 63.
[http://dx.doi.org/10.1186/1744-8069-4-63] [PMID: 19091115]
[96]
Meyer, O.C. Safety and security of Daflon 500 mg in venous insufficiency and in hemorrhoidal disease. Angiology, 1994, 45(6 Pt 2), 579-584.
[http://dx.doi.org/10.1177/000331979404500614] [PMID: 8203791]
[97]
Devi, K.P.; Rajavel, T.; Nabavi, S.F.; Setzer, W.N.; Ahmadi, A.; Mansouri, K.; Nabavi, S.M. Hesperidin: A promising anticancer agent from nature. Ind. Crops Prod., 2015, 76, 582-589.
[http://dx.doi.org/10.1016/j.indcrop.2015.07.051]
[98]
Kumar, S.; Pandey, A.K. Chemistry and biological activities of flavonoids: An overview. ScientificWorldJournal, 2013, 2013, 162750.
[http://dx.doi.org/10.1155/2013/162750] [PMID: 24470791]
[99]
Kean, R.J.; Lamport, D.J.; Dodd, G.F.; Freeman, J.E.; Williams, C.M.; Ellis, J.A.; Butler, L.T.; Spencer, J.P. Chronic consumption of fla-vanone-rich orange juice is associated with cognitive benefits: An 8-wk, randomized, double-blind, placebo-controlled trial in healthy old-er adults. Am. J. Clin. Nutr., 2015, 101(3), 506-514.
[http://dx.doi.org/10.3945/ajcn.114.088518] [PMID: 25733635]
[100]
Francis, S.T.; Head, K.; Morris, P.G.; Macdonald, I.A. The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people. J. Cardiovasc. Pharmacol., 2006, 47(Suppl. 2), S215-S220.
[http://dx.doi.org/10.1097/00005344-200606001-00018] [PMID: 16794461]
[101]
Lamport, D.J.; Pal, D.; Macready, A.L.; Barbosa-Boucas, S.; Fletcher, J.M.; Williams, C.M.; Spencer, J.P.; Butler, L.T. The effects of fla-vanone-rich citrus juice on cognitive function and cerebral blood flow: An acute, randomised, placebo-controlled cross-over trial in healthy, young adults. Br. J. Nutr., 2016, 116(12), 2160-2168.
[http://dx.doi.org/10.1017/S000711451600430X] [PMID: 28091350]
[102]
Alharbi, M.H.; Lamport, D.J.; Dodd, G.F.; Saunders, C.; Harkness, L.; Butler, L.T.; Spencer, J.P. Flavonoid-rich orange juice is associated with acute improvements in cognitive function in healthy middle-aged males. Eur. J. Nutr., 2016, 55(6), 2021-2029.
[http://dx.doi.org/10.1007/s00394-015-1016-9] [PMID: 26280945]
[103]
Zhang, S.; Tomata, Y.; Sugiyama, K.; Sugawara, Y.; Tsuji, I. Citrus consumption and incident dementia in elderly Japanese: The Ohsaki Cohort 2006 Study. Br. J. Nutr., 2017, 117(8), 1174-1180.
[http://dx.doi.org/10.1017/S000711451700109X] [PMID: 28521847]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy