Flavonoid supplements increase neurotrophin activity to modulate inflammation in retinal genetic diseases

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Aysha Karim Kiani
Benedetto Falsini
Lucia Ziccardi
Elena Gusson
Domenica Mangialavori
Francesca Allegrini
Emma Colao
Matteo Bertelli


Retinal degenerative disorders, neurotrophin synthesis, flavonoids supplementation, anti-inflammation, anti-oxidant


Retinal degenerative disorders induce loss of photoreceptors associated with inflammation, and negative remodeling and plasticity of neural retina. Retinal degenerative diseases may have genetic and/or environmental causes. Degeneration of retinal pigment epithelium cells initiates a vicious circle increasing the ongoing inflammation in both retina and choroid. Flavonoids are polyphenolic molecules with antioxidant activity and  dietary intake, specifically of anthocyanins and flavanols, improves oxidative stress and neuro-inflammation. In vitro and ex vivo studies have also revealed biological effects of flavonoids on retinal protection against oxidative stress and inflammation. In this brief review, the protective role of flavonoids against retinal degeneration and inflammation will be discussed along with their therapeutic potential for the treatment of retinal degenerative diseases.


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1. Jones BW, Marc RE, Pfeiffer RL. Retinal degeneration, remodeling and plasticity. In: Webvision: The Organization of the Retina and Visual System. Salt Lake City (UT): University of Utah Health Sciences Center; 2016.
2. Kauppinen A, Paterno JJ, Blasiak J, Salminen A, Kaarniranta K. Inflammation and its role in age-related macular degeneration. Cell Mol Life Sci 2016; 73: 1765-86.
3. Pawelec G, Goldeck D, Derhovanessian E. Inflammation, ageing and chronic disease. Curr Opin Immunol 2014; 29: 23-8.
4. Ferrington DA, Sinha D, Kaarniranta K. Defects in retinal pigment epithelial cell proteolysis and the pathology associated with age-related macular degeneration. Prog Retin Eye Res 2016; 51: 69-89.
5. Telegina DV, Kolosova NG, Kozhevnikova OS. Immunohistochemical localization of NGF, BDNF, and their receptors in a normal and AMD-like rat retina. BMC Med Genomics 2019; 12: 48.
6. Liu C, Chan CB, Ye K. 7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders. Transl Neurodegener 2016; 5: 2.
7. Carito V, Ceccanti M, Chaldakov G, et al. Polyphenols, nerve growth factor, brain-derived neurotrophic factor, and the brain. In: Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease. Cambridge, (MA): Academic Press; 2015.
8. Du X, Hill RA. 7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental disorders. Neurochem Int 2015; 89: 170-80.
9. Moosavi F, Hosseini R, Saso L, Firuzi O. Modulation of neurotrophic signaling pathways by polyphenols. Drug Des Devel Ther 2015; 10: 23-42.
10. Adisakwattana S, Yibchok-Anun S, Charoenlertkul P, Wongsasiripat N. Cyanidin-3-rutinoside alleviates postprandial hyperglycemia and its synergism with acarbose by inhibition of intestinal α-glucosidase. J Clin Biochem Nutr 2011; 49: 36-41.
11. Priya SSL, Devi PR, Madeswaran A. In silico docking studies of RP2 (X-Linked retinitis pigmentosa) protein using anthocyanins as potential inhibitors. Bangladesh Journal of Pharmacology 2013; 8: 292-9.
12. Silva AR, Pinheiro AM, Souza CS, et al. The flavonoid rutin induces astrocyte and microglia activation and regulates TNF-alpha and NO release in primary glial cell cultures. Cell Biol Toxicol 2008; 24: 75-86.
13. Guo Y, Xu J, Li Y, et al. Iridoids and sesquiterpenoids with NGF-potentiating activity from the rhizomes and roots of Valeriana fauriei. Chem Pharm Bull (Tokyo) 2006; 54: 123-5.
14. Vauzour D, Vafeiadou K, Rodriguez-Mateos A, Rendeiro C, Spencer JP. The neuroprotective potential of flavonoids: a multiplicity of effects. Genes Nutr 2008; 3: 115-26.
15. Trajkovska V, Marcussen AB, Vinberg M, Hartvig P, Aznar S, Knudsen GM. Measurements of brain-derived neurotrophic factor: methodological aspects and demographical data. Brain Res Bull 2007; 73: 143-9.
16. Colombo PS, Flamini G, Christodoulou MS, et al. Farinose alpine Primula species: phytochemical and morphological investigations. Phytochemistry 2014; 98: 151-9.
17. Gupta VK, You Y, Li JC, Klistorner A, Graham SL. Protective effects of 7,8-dihydroxyflavone on retinal ganglion and RGC-5 cells against excitotoxic and oxidative stress. J Mol Neurosci 2013; 49: 96–104.
18. Kim KA, Shim SH, Ahn HR, Jung SH. Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage. Toxicol Appl Pharmacol 2013; 269: 109-20.
19. Viringipurampeer IA, Bashar AE, Gregory-Evans CY, Moritz OL, Gregory-Evans K. Targeting inflammation in emerging therapies for genetic retinal disease. Int J Inflam 2013; 2013: 581751.
20. Holan V, Hermankova B, Krulova M, Zajicova A. Cytokine interplay among the diseased retina, inflammatory cells and mesenchymal stem cells - a clue to stem cell-based therapy. World J Stem Cells 2019; 11: 957-67.
21. Kwon JY, Lee KW, Hur HJ, Lee HJ. Peonidin inhibits phorbol-ester-induced COX-2 expression and transformation in JB6 P+ cells by blocking phosphorylation of ERK-1 and -2. Ann N Y Acad Sci 2007; 1095: 513-20.

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