Citrus Polyphenols in Brain Health and Disease: Current Perspectives

Overview

Journal Front Neurosci

Date 2021 Mar 8

PMID 33679318

Citations 23

Authors

Matthew G Pontifex

Mohammad M A H Malik

Emily Connell

Michael Muller

David Vauzour

Affiliations

Soon will be listed here.

Abstract

In addition to essential micronutrients such as vitamin C, citrus fruits represent a considerably rich source of non-essential bioactive compounds, in particular flavanones which form a sub-set of the flavonoid group. Preclinical studies have demonstrated the neuroprotective potential of citrus flavonoids and have highlighted both the well-established (anti-inflammatory and anti-oxidative properties), and newly emerging (influence upon blood-brain barrier function/integrity) mechanistic actions by which these neurological effects are mediated. Encouragingly, results from human studies, although limited in number, appear to support this preclinical basis, with improvements in cognitive performance and disease risk observed across healthy and disease states. Therefore, citrus fruits - both as whole fruit and 100% juices - should be encouraged within the diet for their potential neurological benefit. In addition, there should be further exploration of citrus polyphenols to establish therapeutic efficacy, particularly in the context of well-designed human interventions.

Citing Articles

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References

Antunes M, Jesse C, Ruff J, de Oliveira Espinosa D, Gomes N, Altvater E . Hesperidin reverses cognitive and depressive disturbances induced by olfactory bulbectomy in mice by modulating hippocampal neurotrophins and cytokine levels and acetylcholinesterase activity. Eur J Pharmacol. 2016; 789:411-420. DOI: 10.1016/j.ejphar.2016.07.042. View

Kay C, Pereira-Caro G, Ludwig I, Clifford M, Crozier A . Anthocyanins and Flavanones Are More Bioavailable than Previously Perceived: A Review of Recent Evidence. Annu Rev Food Sci Technol. 2017; 8:155-180. DOI: 10.1146/annurev-food-030216-025636. View

Coutrot A, Schmidt S, Coutrot L, Pittman J, Hong L, Wiener J . Virtual navigation tested on a mobile app is predictive of real-world wayfinding navigation performance. PLoS One. 2019; 14(3):e0213272. PMC: 6422266. DOI: 10.1371/journal.pone.0213272. View

Stevens Y, Van Rymenant E, Grootaert C, Van Camp J, Possemiers S, Masclee A . The Intestinal Fate of Citrus Flavanones and Their Effects on Gastrointestinal Health. Nutrients. 2019; 11(7). PMC: 6683056. DOI: 10.3390/nu11071464. View

McPhee G, Downey L, Stough C . Neurotrophins as a reliable biomarker for brain function, structure and cognition: A systematic review and meta-analysis. Neurobiol Learn Mem. 2020; 175:107298. DOI: 10.1016/j.nlm.2020.107298. View

Gopinath K, Sudhandiran G . Protective effect of naringin on 3-nitropropionic acid-induced neurodegeneration through the modulation of matrix metalloproteinases and glial fibrillary acidic protein. Can J Physiol Pharmacol. 2015; 94(1):65-71. DOI: 10.1139/cjpp-2015-0035. View

Peng H, Cheng F, Huang Y, Chen C, Tsai T . Determination of naringenin and its glucuronide conjugate in rat plasma and brain tissue by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 1998; 714(2):369-74. DOI: 10.1016/s0378-4347(98)00204-7. View

Miners J, Kehoe P, Love S, Zetterberg H, Blennow K . CSF evidence of pericyte damage in Alzheimer's disease is associated with markers of blood-brain barrier dysfunction and disease pathology. Alzheimers Res Ther. 2019; 11(1):81. PMC: 6745071. DOI: 10.1186/s13195-019-0534-8. View

Raza S, Khan M, Ahmad A, Ashafaq M, Khuwaja G, Tabassum R . Hesperidin ameliorates functional and histological outcome and reduces neuroinflammation in experimental stroke. Brain Res. 2011; 1420:93-105. DOI: 10.1016/j.brainres.2011.08.047. View

10.

Erus G, Battapady H, Zhang T, Lovato J, Miller M, Williamson J . Spatial patterns of structural brain changes in type 2 diabetic patients and their longitudinal progression with intensive control of blood glucose. Diabetes Care. 2014; 38(1):97-104. PMC: 4274773. DOI: 10.2337/dc14-1196. View

11.

Lu J, Zhu M, Zhang H, Liu H, Xia B, Wang Y . Neohesperidin attenuates obesity by altering the composition of the gut microbiota in high-fat diet-fed mice. FASEB J. 2020; 34(9):12053-12071. DOI: 10.1096/fj.201903102RR. View

12.

Bai X, Zhang X, Chen L, Zhang J, Zhang L, Zhao X . Protective effect of naringenin in experimental ischemic stroke: down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression. Neurochem Res. 2014; 39(8):1405-15. DOI: 10.1007/s11064-014-1326-y. View

13.

Di Meo F, Lemaur V, Cornil J, Lazzaroni R, Duroux J, Olivier Y . Free radical scavenging by natural polyphenols: atom versus electron transfer. J Phys Chem A. 2013; 117(10):2082-92. DOI: 10.1021/jp3116319. View

14.

Kuzu M, Kandemir F, Yildirim S, Caglayan C, Kucukler S . Attenuation of sodium arsenite-induced cardiotoxicity and neurotoxicity with the antioxidant, anti-inflammatory, and antiapoptotic effects of hesperidin. Environ Sci Pollut Res Int. 2020; 28(9):10818-10831. DOI: 10.1007/s11356-020-11327-5. View

15.

Frank J, Fukagawa N, Bilia A, Johnson E, Kwon O, Prakash V . Terms and nomenclature used for plant-derived components in nutrition and related research: efforts toward harmonization. Nutr Rev. 2019; 78(6):451-458. PMC: 7212822. DOI: 10.1093/nutrit/nuz081. View

16.

Hritcu L, Ionita R, Postu P, Gupta G, Turkez H, Lima T . Antidepressant Flavonoids and Their Relationship with Oxidative Stress. Oxid Med Cell Longev. 2018; 2017:5762172. PMC: 5749298. DOI: 10.1155/2017/5762172. View

17.

Yu Y, Tang D, Kang R . Oxidative stress-mediated HMGB1 biology. Front Physiol. 2015; 6:93. PMC: 4387954. DOI: 10.3389/fphys.2015.00093. View

18.

Kantarci K, Weigand S, Przybelski S, Preboske G, Pankratz V, Vemuri P . MRI and MRS predictors of mild cognitive impairment in a population-based sample. Neurology. 2013; 81(2):126-33. PMC: 3770173. DOI: 10.1212/WNL.0b013e31829a3329. View

19.

Musaeus C, Gleerup H, Hogh P, Waldemar G, Hasselbalch S, Simonsen A . Cerebrospinal Fluid/Plasma Albumin Ratio as a Biomarker for Blood-Brain Barrier Impairment Across Neurodegenerative Dementias. J Alzheimers Dis. 2020; 75(2):429-436. DOI: 10.3233/JAD-200168. View

20.

Chen B, Dowlatshahi D, MacQueen G, Wang J, Young L . Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry. 2001; 50(4):260-5. DOI: 10.1016/s0006-3223(01)01083-6. View