The Roles of Flavonols/Flavonoids in Neurodegeneration and Neuroinflammation

Author(s): Zehra Calis, Rasim Mogulkoc*, Abdülkerim Kasim Baltaci

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 20 , Issue 15 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


The inflammatory process in the human body is a physiological response involving many cellular types and mediators. It results in scar formation to separate the damaged area from the surrounding healthy tissue. Because of increased blood-brain barrier permeability following inflammation, leukocytes infiltrate the CNS and are also supplemented by proinflammatory mediators. However, an acute inflammatory process after cerebral trauma or stroke may also result in a prolonged lesion formation, leading to a severe neuronal loss. The prolonged inflammatory process in the CNS may cause serious damage to the neuronal system. It may lead to CNS damage in such a way that endangers functional integration and proinflammatory system balance. Effects of different flavonoid species on ischemia-reperfusion injury and cognition and function have also been shown in experimental studies. Flavonoids are presented broadly in plants and diets. They are believed to have various bioactive effects including anti-viral, anti-inflammatory, cardioprotective, anti-diabetic, anti-cancer, anti-aging, etc. Quercetine is the predominant dietary flavonoid. Main sources are tea, onion, and apple. It is demonstrated that the frequently consumed food like soybean, peanut, mustard, rice, sesame, olive, potatoes, onion, and oats contain flavonoids. Catechin and its derivates which are isolated from tea leaves have antioxidant activity but in low doses, their prooxidant effects are also reported. Ipriflavone which is a synthetic flavonoid may increase total calcium in bone. In this review, the effects of flavonoids species on the inflammatory process in the neurodegenerative process were examined as general.

Keywords: Antidiabetic, neuronal system, ipriflavone, anti-inflammatory, cardioprotective, anti-cancer.

Dajas, F.; Andrés, A.C.; Florencia, A.; Carolina, E.; Felicia, R.M. Neuroprotective actions of flavones and flavonols: Mechanisms and relationship to flavonoid structural features. Cent. Nerv. Syst. Agents Med. Chem., 2013, 13(1), 30-35.
[] [PMID: 23092407]
Wang, D.; Sun-Waterhouse, D.; Li, F.; Xin, L.; Li, D. MicroRNAs as molecular targets of quercetin and its derivatives underlying their biological effects: A preclinical strategy. Crit. Rev. Food Sci. Nutr., 2018, 15, 1-13.
[] [PMID: 29446655]
Li, W.; Yalcin, M.; Lin, Q.; Ardawi, M.M.; Mousa, S.A. Self-assembly of green tea catechin derivatives in nanoparticles for oral lycopene delivery. J. Control. Release, 2017, 248, 117-124.
[] [PMID: 28077264]
Liu, Z.; Zhou, T.; Ziegler, A.C.; Dimitrion, P.; Zuo, L. Oxidative stress in neurodegenerative diseases: From molecular mechanisms to clinical applications. Oxid. Med. Cell. Longev., 2017, 2017 2525967.
[] [PMID: 28785371]
Balasundaram, G.; Kwang, T.W.; Wang, S. cDNA microarray assays to evaluate immune responses following intracranial injection of baculoviral vectors in non-human primates. J. Neurochem., 2017, 140(2), 320-333.
[] [PMID: 27805764]
Dai, Y.; Zhang, H.; Zhang, J.; Yan, M. Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-κB pathway. Chem. Biol. Interact., 2018, 284, 32-40.
[] [PMID: 29454613]
Maldonado-Ruiz, R.; Fuentes-Mera, L.; Camacho, A. Central modulation of neuroinflammation by neuropeptides and energy-sensing hormones during obesity. BioMed Res. Int., 2017, 2017, 7949582.
[] [PMID: 28913358]
Höglund, K.; Salter, H. Molecular biomarkers of neurodegeneration. Expert Rev. Mol. Diagn., 2013, 13(8), 845-861.
[] [PMID: 24151849]
Uzum, G.; Bahçekapılı, N.; Baltaci, A.K.; Mogulkoc, R.; Ziylan, Y.Z. Pre- and post-estrogen administration in global cerebral ischemia reduces blood-brain barrier breakdown in ovariectomized rats. Acta Physiol. Hung., 2015, 102(1), 60-66.
[] [PMID: 25804390]
Caliskan, M.; Mogulkoc, R.; Baltaci, A.K.; Menevse, E. The effect of 3′,4′-Dihydroxyflavonol on lipid peroxidation in rats with cerebral ischemia reperfusion injury. Neurochem. Res., 2016, 41(7), 1732-1740.
[] [PMID: 27017510]
Spagnuolo, C.; Moccia, S.; Russo, G.L. Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur. J. Med. Chem., 2018, 153, 105-115.
[] [PMID: 28923363]
McManus, R.M.; Heneka, M.T. Role of neuroinflammation in neurodegeneration: New insights. Alzheimers Res. Ther., 2017, 9(1), 14.
[] [PMID: 28259169]
Chen, X.; Shi, X.; Zhang, X.; Lei, H.; Long, S.; Su, H.; Pei, Z.; Huang, R. Scutellarin attenuates hypertension-induced expression of brain Toll-like receptor 4/nuclear factor kappa B. Mediators Inflamm., 2013, 2013, 432623.
[] [PMID: 24223475]
Spencer, J.P.; Vafeiadou, K.; Williams, R.J.; Vauzour, D. Neuroinflammation: Modulation by flavonoids and mechanisms of action. Mol. Aspects Med., 2012, 33(1), 83-97.
[] [PMID: 22107709]
Strober, L.B.; Arnett, P.A. Assessment of depression in three medically ill, elderly populations: Alzheimer’s disease, Parkinson’s disease, and stroke. Clin. Neuropsychol., 2009, 23(2), 205-230.
[] [PMID: 18609323]
Du, Y.; Graves, S.M. Spiny projection neuron dynamics in toxin and transgenic models of parkinson’s disease. Front. Neural Circuits, 2019, 13, 17.
[] [PMID: 30930753]
Sehanovic, A.; Dostovic, Z.; Smajlovic, D.; Avdibegovic, E. Quality of life in patients suffering from Parkinson’s disease and multiple sclerosis. Med. Arh., 2011, 65(5), 291-294.
[] [PMID: 22073854]
Pandey, K.B.; Rizvi, S.I. Plant polyphenols as dietary antioxidants in human health and disease. Oxid. Med. Cell. Longev., 2009, 2(5), 270-278.
[] [PMID: 20716914]
Kim, H.G.; Ju, M.S.; Ha, S.K.; Lee, H.; Lee, H.; Kim, S.Y.; Oh, M.S. Acacetin protects dopaminergic cells against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neuroinflammation in vitro and in vivo. Biol. Pharm. Bull., 2012, 35(8), 1287-1294.
[] [PMID: 22863927]
Doo, A.R.; Kim, S.N.; Park, J.Y.; Cho, K.H.; Hong, J.; Eun-Kyung, K.; Moon, S.K.; Jung, W.S.; Lee, H.; Jung, J.H.; Park, H.J. Neuroprotective effects of an herbal medicine, Yi-Gan San on MPP+/MPTP-induced cytotoxicity in vitro and in vivo. J. Ethnopharmacol., 2010, 131(2), 433-442.
[] [PMID: 20633628]
Fragkouli, A.; Doxakis, E. miR-7 and miR-153 protect neurons against MPP(+)-induced cell death via upregulation of mTOR pathway. Front. Cell. Neurosci., 2014, 8, 182.
[] [PMID: 25071443]
Yilmaz, M.; Yilmaz, N. The role of Vitamin D in Brain and related neurological diseases. J Clin Exp Invest., 2013, 4, 3.
Cunill, V.; Massot, M.; Clemente, A.; Calles, C.; Andreu, V.; Núñez, V.; López-Gómez, A.; Díaz, R.M.; Jiménez, M.L.R.; Pons, J.; Vives-Bauzà, C.; Ferrer, J.M. Relapsing-Remitting multiple sclerosis is characterized by a t follicular cell pro-inflammatory shift, reverted by dimethyl fumarate treatment. Front. Immunol., 2018, 9, 1097.
[] [PMID: 29896193]
Dörr, J.; Döring, A.; Paul, F. Can we prevent or treat multiple sclerosis by individualised vitamin D supply? EPMA J., 2013, 4(1), 4.
[] [PMID: 23356351]
Patejdl, R.; Zettl, U.K. Spasticity in multiple sclerosis: Contribution of inflammation, autoimmune mediated neuronal damage and therapeutic interventions. Autoimmun. Rev., 2017, 16(9), 925-936.
[] [PMID: 28698092]
Baeke, F.; Takiishi, T.; Korf, H.; Gysemans, C.; Mathieu, C.; Vitamin, D. Modulator of the immune system. Curr. Opin. Pharmacol., 2010, 10(4), 482-496.
[] [PMID: 20427238]
Danikowski, K.M.; Jayaraman, S.; Prabhakar, B.S. Regulatory T cells in multiple sclerosis and myasthenia gravis. J. Neuroinflammation, 2017, 14(1), 117.
[] [PMID: 28599652]
Niu, H.; Alvarez-Alvarez, I.; Guillen-Grima, F.; Al-Rahamneh, M.J.; Aguinaga-Ontoso, I. Trends of mortality from Alzheimer’s disease in the European Union, 1994-2013. Eur. J. Neurol., 2017, 24(6), 858-866.
[] [PMID: 28544405]
Sancesario, G.M.; Bernardini, S. Diagnosis of neurodegenerative dementia: where do we stand, now? Ann. Transl. Med., 2018, 6(17), 340.
[] [PMID: 30306079]
Keser, S.; Celik, S.; Turkoglu, S. Total phenolic contents and free-radical scavenging activities of grape (Vitis vinifera L.) and grape products. Int. J. Food Sci. Nutr., 2013, 64(2), 210-216.
[] [PMID: 23025419]
Mandel, S.; Amit, T.; Bar-Am, O.; Youdim, M.B. Iron dysregulation in Alzheimer’s disease: multimodal brain permeable iron chelating drugs, possessing neuroprotective-neurorescue and amyloid precursor protein-processing regulatory activities as therapeutic agents. Prog. Neurobiol., 2007, 82(6), 348-360.
[] [PMID: 17659826]
Lefèvre-Arbogast, S.; Gaudout, D.; Bensalem, J.; Letenneur, L.; Dartigues, J.F.; Hejblum, B.P.; Féart, C.; Delcourt, C.; Samieri, C. Pattern of polyphenol intake and the long-term risk of dementia in older persons. Neurology, 2018, 90(22), e1979-e1988.
[] [PMID: 29703769]
Sarubbo, F.; Moranta, D.; Asensio, V.J.; Miralles, A.; Esteban, S. Effects of resveratrol and other polyphenols on the most common brain age-related diseases. Curr. Med. Chem., 2017, 24(38), 4245-4266.
[] [PMID: 28738770]
Bhullar, K.S.; Rupasinghe, H.P. Polyphenols: Multipotent therapeutic agents in neurodegenerative diseases. Oxid. Med. Cell. Longev., 2013, 2013, 891748.
[] [PMID: 23840922]
Xu, P.; Zhang, M.; Sheng, R.; Ma, Y. Synthesis and biological evaluation of deferiprone-resveratrol hybrids as antioxidants, Aβ1-42 aggregation inhibitors and metal-chelating agents for Alzheimer’s disease. Eur. J. Med. Chem., 2017, 127, 174-186.
[] [PMID: 28061347]
Jayasena, T.; Poljak, A.; Smythe, G.; Braidy, N.; Münch, G.; Sachdev, P. The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer’s disease. Ageing Res. Rev., 2013, 12(4), 867-883.
[] [PMID: 23831960]
Farzaei, M.H.; Tewari, D.; Momtaz, S.; Argüelles, S.; Nabavi, S.M. Targeting ERK signaling pathway by polyphenols as novel therapeutic strategy for neurodegeneration. Food Chem. Toxicol., 2018, 120, 183-195.
[] [PMID: 29981370]
Lakey-Beitia, J.; Berrocal, R.; Rao, K.S.; Durant, A.A. Polyphenols as therapeutic molecules in Alzheimer’s disease through modulating amyloid pathways. Mol. Neurobiol., 2015, 51(2), 466-479.
[] [PMID: 24826916]
Mandel, S.A.; Avramovich-Tirosh, Y.; Reznichenko, L.; Zheng, H.; Weinreb, O.; Amit, T.; Youdim, M.B. Multifunctional activities of green tea catechins in neuroprotection. Modulation of cell survival genes, iron-dependent oxidative stress and PKC signaling pathway. Neurosignals, 2005, 14(1-2), 46-60.
[] [PMID: 15956814]
Kim, D.S.; Kim, J.Y.; Han, Y. Curcuminoids in neurodegenerative diseases. Recent Patents CNS Drug Discov., 2012, 7(3), 184-204.
[] [PMID: 22742420]
Maiti, P.; Dunbar, G.L. Use of curcumin, a natural polyphenol for targeting molecular pathways in treating age-related neurodegenerative diseases. Int. J. Mol. Sci., 2018, 19(6) E1637.
[] [PMID: 29857538]
Hoang, P.T.; Chalif, J.I.; Bikoff, J.B.; Jessell, T.M.; Mentis, G.Z.; Wichterle, H. Subtype diversification and synaptic specificity of stem cell-derived spinal interneurons. Neuron, 2018, 100(1), 135-149.e7.
[] [PMID: 30308166]
Laurent, C.; Buée, L.; Blum, D. Tau and neuroinflammation: What impact for Alzheimer’s Disease and Tauopathies? Biomed. J., 2018, 41(1), 21-33.
[] [PMID: 29673549]
De Luca, C.; Colangelo, A.M.; Alberghina, L.; Papa, M. Neuro-immune hemostasis: Homeostasis and diseases in the central nervous system. Front. Cell. Neurosci., 2018, 12, 459.
[] [PMID: 30534057]
Rahimifard, M.; Maqbool, F.; Moeini-Nodeh, S.; Niaz, K.; Abdollahi, M.; Braidy, N.; Nabavi, S.M.; Nabavi, S.F. Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation. Ageing Res. Rev., 2017, 36, 11-19.
[] [PMID: 28235660]
Waschek, J.A. VIP and PACAP: neuropeptide modulators of CNS inflammation, injury, and repair. Br. J. Pharmacol., 2013, 169(3), 512-523.
[] [PMID: 23517078]
Trias, E.; King, P.H.; Si, Y.; Kwon, Y.; Varela, V.; Ibarburu, S.; Kovacs, M.; Moura, I.C.; Beckman, J.S.; Hermine, O.; Barbeito, L. Mast cells and neutrophils mediate peripheral motor pathway degeneration in ALS. JCI Insight, 2018, 3(19) 123249.
[] [PMID: 30282815]
Doursout, M.F.; Schurdell, M.S.; Young, L.M.; Osuagwu, U.; Hook, D.M.; Poindexter, B.J.; Schiess, M.C.; Bick, D.L.; Bick, R.J. Inflammatory cells and cytokines in the olfactory bulb of a rat model of neuroinflammation; insights into neurodegeneration? J. Interferon Cytokine Res., 2013, 33(7), 376-383.
[] [PMID: 23600861]
Cali, C.; Lopatar, J.; Petrelli, F.; Pucci, L.; Bezzi, P. G-protein coupled receptor-evoked glutamate exocytosis from astrocytes: Role of prostaglandins. Neural Plast., 2014, 2014, 254574.
[] [PMID: 24551459]
Candiracci, M.; Piatti, E.; Dominguez-Barragán, M.; García-Antrás, D.; Morgado, B.; Ruano, D.; Gutiérrez, J.F.; Parrado, J.; Castaño, A. Anti-inflammatory activity of a honey flavonoid extract on lipopolysaccharide-activated N13 microglial cells. J. Agric. Food Chem., 2012, 60(50), 12304-12311.
[] [PMID: 23176387]
Chhor, V.; Le Charpentier, T.; Lebon, S.; Oré, M-V.; Celador, I.L.; Josserand, J.; Degos, V.; Jacotot, E.; Hagberg, H.; Sävman, K.; Mallard, C.; Gressens, P.; Fleiss, B. Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro. Brain Behav. Immun., 2013, 32, 70-85.
[] [PMID: 23454862]
Block, M.L.; Hong, J.S. Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism. Prog. Neurobiol., 2005, 76(2), 77-98.
[] [PMID: 16081203]
Sevenich, L. Brain-Resident microglia and blood-borne macrophages orchestrate central nervous system inflammation in neurodegenerative disorders and brain cancer. Front. Immunol., 2018, 9, 697.
[] [PMID: 29681904]
Chen, L.; Deng, H.; Cui, H.; Fang, J.; Zuo, Z.; Deng, J.; Li, Y.; Wang, X.; Zhao, L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 2017, 9(6), 7204-7218.
[PMID: 29467962]
Hussain, G.; Zhang, L.; Rasul, A.; Anwar, H.; Sohail, M.U.; Razzaq, A.; Aziz, N.; Shabbir, A.; Ali, M.; Sun, T. Role of plant-derived flavonoids and their mechanism in attenuation of alzheimer’s and parkinson’s diseases: An update of recent data. Molecules, 2018, 23(4) E814.
[] [PMID: 29614843]
Subedi, L.; Lee, J.H.; Yumnam, S.; Ji, E.; Kim, S.Y. Anti-Inflammatory Effect of Sulforaphane on LPS-Activated Microglia Potentially through JNK/AP-1/NF-κB Inhibition and Nrf2/HO-1 Activation. Cells, 2019, 8(2) E194.
[] [PMID: 30813369]
Zindler, E.; Zipp, F. Neuronal injury in chronic CNS inflammation. Best Pract. Res. Clin. Anaesthesiol., 2010, 24(4), 551-562.
[] [PMID: 21619866]
Baker, R.G.; Hayden, M.S.; Ghosh, S. NF-κB, inflammation, and metabolic disease. Cell Metab., 2011, 13(1), 11-22.
[] [PMID: 21195345]
Jung, Y.C.; Kim, M.E.; Yoon, J.H.; Park, P.R.; Youn, H-Y.; Lee, H-W.; Lee, J.S. Anti-inflammatory effects of galangin on lipopolysaccharide-activated macrophages via ERK and NF-κB pathway regulation. Immunopharmacol. Immunotoxicol., 2014, 36(6), 426-432.
[] [PMID: 25270721]
Rani, N.; Bharti, S.; Krishnamurthy, B.; Bhatia, J.; Sharma, C.; Kamal, M.A.; Ojha, S.; Arya, D.S. Pharmacological properties and therapeutic potential of naringenin: A citrus flavonoid of pharmaceutical promise. Curr. Pharm. Des., 2016, 22(28), 4341-4359.
[ ] [PMID: 27238365]
Hojung, H.; Conrad, T.; Lewis, N.E. Metabolic pathway evolution and cellular objectives. Curr. Opin. Biotechnol., 2011, 22, 595-600.
[] [PMID: 21481583]
Sawmiller, D.; Habib, A.; Li, S.; Darlington, D.; Hou, H.; Tian, J.; Shytle, R.D.; Smith, A.; Giunta, B.; Mori, T.; Tan, J. Diosmin reduces cerebral Aβ levels, tau hyperphosphorylation, neuroinflammation, and cognitive impairment in the 3xTg-AD mice. J. Neuroimmunol., 2016, 299, 98-106.
[] [PMID: 27725131]
Sarbu, L.G.; Bahrin, L.G.; Babii, C.; Stefan, M.; Birsa, M.L. Synthetic flavonoids with antimicrobial activity: A review. J. Appl. Microbiol., 2019, 127(5), 1282-1290.
[] [PMID: 30934143]
McDougall, G.J. Phenolic-enriched foods: Sources and processing for enhanced health benefits. Proc. Nutr. Soc., 2017, 76(2), 163-171.
[] [PMID: 27804893]
Sarbu, L.G.; Bahrin, L.G.; Babii, C.; Stefan, M.; Birsa, M.L. Synthetic flavonoids with antimicrobial activity: A review. J. Appl. Microbiol., 2019.
[] [PMID: 30934143]
Babii, C.; Mihalache, G.; Bahrin, L.G.; Neagu, A.N.; Gostin, I.; Mihai, C.T.; Sârbu, L.G.; Birsa, L.M.; Stefan, M. A novel synthetic flavonoid with potent antibacterial properties: In vitro activity and proposed mode of action. PLoS One, 2018, 13(4) e0194898.
[] [PMID: 29617411]
Roy, S.K.; Kumari, N.; Gupta, S.; Pahwa, S.; Nandanwar, H.; Jachak, S.M. 7-Hydroxy-(E)-3-phenylmethylene-chroman-4-one analogues as efflux pump inhibitors against Mycobacterium smegmatis mc2 155. Eur. J. Med. Chem., 2013, 66, 499-507.
[] [PMID: 23832254]
Moreira, J.; Ribeiro, D.; Silva, P.M.A.; Nazareth, N.; Monteiro, M.; Palmeira, A.; Saraiva, L.; Pinto, M.; Bousbaa, H.; Cidade, H. New alkoxy flavone derivatives targeting caspases: synthesis and antitumor activity evaluation. Molecules, 2018, 24(1) E129.
[] [PMID: 30602686]
Bonet, B.; Otero, P.; Viana, M.; Herrera, E. Antioxidant and prooxidant effects of vitamin C and flavonoids on LDL oxidation.Abstracts of papers; , 1996, p. 75.
Auroma, O.I.; Murcia, A. Evaluation of the antioxidant and prooxidant actions of gallic acid and its derivates. J. Agric. Food Chem., 1993, 41, 1880-1885.
Cao, G.; Sofic, E.; Prior, R.L. Antioxidant and prooxidant behavior of flavonoids: structure-activity relationships. Free Radic. Biol. Med., 1997, 22(5), 749-760.
[] [PMID: 9119242]
Yang, T.; Liu, Y.; Huang, X.; Zhang, R.; Yang, C.; Zhou, J.; Zhang, Y.; Wan, J.; Shi, S. Quercetin-3-O-β-D-glucoside decreases the bioavailability of cyclosporin A through regulation of drug metabolizing enzymes, transporters and nuclear receptors in rats. Mol. Med. Rep., 2018, 18(3), 2599-2612.
[] [PMID: 30015887]
Suganthy, N.; Devi, K.P.; Nabavi, S.F.; Braidy, N.; Nabavi, S.M. Bioactive effects of quercetin in the central nervous system: Focusing on the mechanisms of actions. Biomed. Pharmacother., 2016, 84, 892-908.
[] [PMID: 27756054]
Khan, A.; Ali, T.; Rehman, S.U.; Khan, M.S.; Alam, S.I.; Ikram, M.; Muhammad, T.; Saeed, K.; Badshah, H.; Kim, M.O. Neuroprotective effect of quercetin against the detrimental effects of lps in the adult mouse brain. Front. Pharmacol., 2018, 9, 1383.
[] [PMID: 30618732]
Bournival, J.; Plouffe, M.; Renaud, J.; Provencher, C.; Martinoli, M.G. Quercetin and sesamin protect dopaminergic cells from MPP+-induced neuroinflammation in a microglial (N9)-neuronal (PC12) coculture system. Oxid. Med. Cell. Longev., 2012, 2012, 921941.
[] [PMID: 22919443]
Testa, G.; Gamba, P.; Badilli, U.; Gargiulo, S.; Maina, M.; Guina, T.; Calfapietra, S.; Biasi, F.; Cavalli, R.; Poli, G.; Leonarduzzi, G. Loading into nanoparticles improves quercetin’s efficacy in preventing neuroinflammation induced by oxysterols. PLoS One, 2014, 9(5) e96795.
[] [PMID: 24802026]
Rodrigues, R.; Petersen, R.B.; Perry, G. Parallels between major depressive disorder and Alzheimer’s disease: Role of oxidative stress and genetic vulnerability. Cell. Mol. Neurobiol., 2014, 34(7), 925-949.
[] [PMID: 24927694]
Mehta, V.; Parashar, A.; Udayabanu, M. Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress. Physiol. Behav., 2017, 171, 69-78.
[] [PMID: 28069457]
Kang, C.H.; Choi, Y.H.; Moon, S.K.; Kim, W.J.; Kim, G.Y. Quercetin inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-κB pathway and activating the Nrf2-dependent HO-1 pathway. Int. Immunopharmacol., 2013, 17(3), 808-813.
[] [PMID: 24076371]
Sun, G.Y.; Chen, Z.; Jasmer, K.J.; Chuang, D.Y.; Gu, Z.; Hannink, M.; Simonyi, A. Quercetin attenuates inflammatory responses in BV-2 microglial cells: role of MAPKs on the Nrf2 pathway and induction of heme oxygenase-1. PLoS One, 2015, 10(10) e0141509.
[] [PMID: 26505893]
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.
[] [PMID: 25434716]
Xu, P.X.; Wang, S.W.; Yu, X.L.; Su, Y.J.; Wang, T.; Zhou, W.W.; Zhang, H.; Wang, Y.J.; Liu, R.T. Rutin improves spatial memory in Alzheimer’s disease transgenic mice by reducing Aβ oligomer level and attenuating oxidative stress and neuroinflammation. Behav. Brain Res., 2014, 264, 173-180.
[] [PMID: 24512768]
Hao, G.; Dong, Y.; Huo, R.; Wen, K.; Zhang, Y.; Liang, G. Rutin inhibits neuroinflammation and provides neuroprotection in an experimental rat model of subarachnoid hemorrhage, possibly through suppressing the RAGE-NF-κB inflammatory signaling pathway. Neurochem. Res., 2016, 41(6), 1496-1504.
[] [PMID: 26869040]
Lue, L.F.; Yan, S.D.; Stern, D.M.; Walker, D.G. Preventing activation of receptor for advanced glycation endproducts in Alzheimer’s disease. Curr. Drug Targets CNS Neurol. Disord., 2005, 4(3), 249-266.
[] [PMID: 15975028]
Yu, L.; Chen, C.; Wang, L.F.; Kuang, X.; Liu, K.; Zhang, H.; Du, J.R. Neuroprotective effect of kaempferol glycosides against brain injury and neuroinflammation by inhibiting the activation of NF-κB and STAT3 in transient focal stroke. PLoS One, 2013, 8(2) e55839.
[] [PMID: 23437066]
Gregory, L. Hostetler, Robin A Ralston, Steven J Schwartz. Flavones: Food Sources, Bioavailability, Metabolism, and Bioactivity. Adv. Nutr., 2017, 8, 423-435.
Yang, Y.; Wang, L.; Wu, Y.; Su, D.; Wang, N.; Wang, J.; Shi, C.; Lv, L.; Zhang, S. Tanshinol suppresses inflammatory factors in a rat model of vascular dementia and protects LPS-treated neurons via the MST1-FOXO3 signaling pathway. Brain Res., 2016, 1646, 304-314.
[] [PMID: 27317635]
Burton, M.D.; Rytych, J.L.; Amin, R.; Johnson, R.W. Dietary luteolin reduces proinflammatory microglia in the brain of senescent mice. Rejuvenation Res., 2016, 19(4), 286-292.
[] [PMID: 26918466]
Dirscherl, K.; Karlstetter, M.; Ebert, S.; Kraus, D.; Hlawatsch, J.; Walczak, Y.; Moehle, C.; Fuchshofer, R.; Langmann, T. Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype. J. Neuroinflammation, 2010, 7, 3.
[] [PMID: 20074346]
Jang, S.; Kelley, K.W.; Johnson, R.W. Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proc. Natl. Acad. Sci. USA, 2008, 105(21), 7534-7539.
[] [PMID: 18490655]
Zhu, L.; Bi, W.; Lu, D.; Zhang, C.; Shu, X.; Lu, D. Luteolin inhibits SH-SY5Y cell apoptosis through suppression of the nuclear transcription factor-κB, mitogen-activated protein kinase and protein kinase B pathways in lipopolysaccharide-stimulated cocultured BV2 cells. Exp. Ther. Med., 2014, 7(5), 1065-1070.
[] [PMID: 24940388]
Rezai-Zadeh, K.; Ehrhart, J.; Bai, Y.; Sanberg, P.R.; Bickford, P.; Tan, J.; Shytle, R.D. Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression. J. Neuroinflammation, 2008, 5, 41.
[] [PMID: 18817573]
Patil, S.P.; Jain, P.D.; Sancheti, J.S.; Ghumatkar, P.J.; Tambe, R.; Sathaye, S. Neuroprotective and neurotrophic effects of Apigenin and Luteolin in MPTP induced parkinsonism in mice. Neuropharmacology, 2014, 86, 192-202.
[] [PMID: 25087727]
Ginwala, R.; McTish, E.; Raman, C.; Singh, N.; Nagarkatti, M.; Nagarkatti, P.; Sagar, D.; Jain, P.; Khan, Z.K. Apigenin, a natural flavonoid, attenuates EAE severity through the modulation of dendritic cell and other immune cell functions. J. Neuroimmune Pharmacol., 2016, 11(1), 36-47.
[] [PMID: 26040501]
Funakoshi-Tago, M.; Nakamura, K.; Tago, K.; Mashino, T.; Kasahara, T. Anti-inflammatory activity of structurally related flavonoids, Apigenin, Luteolin and Fisetin. Int. Immunopharmacol., 2011, 11(9), 1150-1159.
[] [PMID: 21443976]
Yuan, Y.; Zha, H.; Rangarajan, P.; Ling, E-A.; Wu, C. Anti-inflammatory effects of Edaravone and Scutellarin in activated microglia in experimentally induced ischemia injury in rats and in BV-2 microglia. BMC Neurosci., 2014, 15, 125.
[] [PMID: 25416145]
Lee, Y-J.; Choi, D-Y.; Yun, Y-P.; Han, S.B.; Oh, K-W.; Hong, J.T. Epigallocatechin-3-gallate prevents systemic inflammation-induced memory deficiency and amyloidogenesis via its anti-neuroinflam-matory properties. J. Nutr. Biochem., 2013, 24(1), 298-310.
[] [PMID: 22959056]
Oz, M.; Demir, E.A.; Caliskan, M.; Mogulkoc, R.; Baltaci, A.K.; Nurullahoglu Atalik, K.E. 3′,4′-Dihydroxyflavonol attenuates spatial learning and memory impairments in global cerebral ischemia. Nutr. Neurosci., 2017, 20(2), 119-126.
[] [PMID: 25290491]
Wu, K.J.; Hsieh, M.T.; Wu, C.R.; Wood, W.G.; Chen, Y.F. Green tea extract ameliorates learning and memory deficits in ischemic rats via its actiandcomponent polyphenol epigallocatechin-3-gallate by modulation of oxidatiandstress and neuroinflammation. Evid. Based Complement. Alternat. Med., 2012, 2012, 163106.
[] [PMID: 22919410]
Herges, K.; Millward, J.M.; Hentschel, N.; Infante-Duarte, C.; Aktas, O.; Zipp, F. Neuroprotective effect of combination therapy of glatiramer acetate and epigallocatechin-3-gallate in neuroinflammation. PLoS One, 2011, 6(10) e25456.
[] [PMID: 22022398]
Cheng-Chung Wei, J.; Huang, H.C.; Chen, W.J.; Huang, C.N.; Peng, C.H.; Lin, C.L. Epigallocatechin gallate attenuates amyloid β-induced inflammation and neurotoxicity in EOC 13.31 microglia. Eur. J. Pharmacol., 2016, 770, 16-24.
[] [PMID: 26643169]
Li, J.; Ye, L.; Wang, X.; Liu, J.; Wang, Y.; Zhou, Y.; Ho, W. (-)-Epigallocatechin gallate inhibits endotoxin-induced expression of inflammatory cytokines in human cerebral microvascular endothelial cells. J. Neuroinflammation, 2012, 9, 161.
[] [PMID: 22768975]
Anandhan, A.; Essa, M.M.; Manivasagam, T. Therapeutic attenuation of neuroinflammation and apoptosis by black tea theaflavin in chronic MPTP/probenecid model of Parkinson’s disease. Neurotox. Res., 2013, 23(2), 166-173.
[] [PMID: 22669749]
Lee, S.B.; Choi, E.H.; Jeong, K.H.; Kim, K.S.; Shim, S.M.; Kim, G.H. Effect of catechins and high-temperature-processed green tea extract on scavenging reactive oxygen species and preventing Aβ1-42 fibrils’ formation in brain microvascular endothelium. Nutr. Neurosci., 2020, 23(5), 363-373.
[] [PMID: 30111271]
Monteiro, A.F.M.; Viana, J.O.; Nayarisseri, A.; Zondegoumba, E.N.; Mendonça, Junior, F.J.B.; Scotti, M.T.; Scotti, L. Computational studies applied to flavonoids against Alzheimer’s and Parkinson’s diseases. Oxid. Med. Cell. Longev., 2018, 2018, 7912765.
[] [PMID: 30693065]
Wu, L.H.; Lin, C.; Lin, H.Y.; Liu, Y.S.; Wu, C.Y.; Tsai, C.F.; Chang, P.C.; Yeh, W.L.; Lu, D.Y. Naringenin suppresses neuroinflammatory responses through inducing suppressor of cytokine signaling 3 expression. Mol. Neurobiol., 2016, 53(2), 1080-1091.
[] [PMID: 25579382]
Vafeiadou, K.; Vauzour, D.; Lee, H.Y.; Rodriguez-Mateos, A.; Williams, R.J.; Spencer, J.P. The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury. Arch. Biochem. Biophys., 2009, 484(1), 100-109.
[] [PMID: 19467635]
Shi, L.B.; Tang, P.F.; Zhang, W.; Zhao, Y.P.; Zhang, L.C.; Zhang, H. Naringenin inhibits spinal cord injury-induced activation of neutrophils through miR-223. Gene, 2016, 592(1), 128-133.
[] [PMID: 27432064]
Li, M.; Shao, H.; Zhang, X.; Qin, B. Hesperidin alleviates lipopolysaccharide-induced neuroinflammation in mice by promoting the miRNA-132 pathway. Inflammation, 2016, 39(5), 1681-1689.
[] [PMID: 27378528]
Prior, R.L.; Wu, X. Anthocyanins: structural characteristics that result in unique metabolic patterns and biological activities. Free Radic. Res., 2006, 40(10), 1014-1028.
[] [PMID: 17015246]
Carvalho, F.B.; Gutierres, J.M.; Bueno, A.; Agostinho, P.; Zago, A.M.; Vieira, J.; Frühauf, P.; Cechella, J.L.; Nogueira, C.W.; Oliveira, S.M.; Rizzi, C.; Spanevello, R.M.; Duarte, M.M.F.; Duarte, T.; Dellagostin, O.A.; Andrade, C.M. Anthocyanins control neuroinflammation and consequent memory dysfunction in mice exposed to lipopolysaccharide. Mol. Neurobiol., 2017, 54(5), 3350-3367.
[] [PMID: 27167130]
Khan, M.S.; Ali, T.; Kim, M.W.; Jo, M.H.; Jo, M.G.; Badshah, H.; Kim, M.O. Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex. Neurochem. Int., 2016, 100, 1-10.
[] [PMID: 27522965]
Rehman, S.U.; Shah, S.A.; Ali, T.; Chung, J.I.; Kim, M.O. Anthocyanins reversed D-galactose-induced oxidatiandstress and neuroinflammation mediated cognitiandimpairment in adult rats. Mol. Neurobiol., 2017, 54(1), 255-271.
[] [PMID: 26738855]
Carvalho, F.B.; Gutierres, J.M.; Bohnert, C.; Zago, A.M.; Abdalla, F.H.; Vieira, J.M.; Palma, H.E.; Oliveira, S.M.; Spanevello, R.M.; Duarte, M.M.; Lopes, S.T.; Aiello, G.; Amaral, M.G.; Pippi, N.L.; Andrade, C.M. Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination. J. Nutr. Biochem., 2015, 26(4), 378-390.
[] [PMID: 25632845]
Meireles, M.; Marques, C.; Norberto, S.; Santos, P.; Fernandes, I.; Mateus, N.; Faria, A.; Calhau, C. Anthocyanin effects on microglia M1/M2 phenotype: Consequence on neuronal fractalkine expression. Behav. Brain Res., 2016, 305, 223-228.
[] [PMID: 26965567]
Pang, Y.; Zhang, Y.; Huang, L.; Xu, L.; Wang, K.; Wang, D.; Guan, L.; Zhang, Y.; Yu, F.; Chen, Z.; Xie, X. Effects and Mechanisms of Total Flavonoids from Blumea balsamifera (L.) DC. on Skin Wound in Rats. Int. J. Mol. Sci., 2017, 18(12) E2766.
[] [PMID: 29257119]
Wang, Y.; Li, W.; Wang, M.; Lin, C.; Li, G.; Zhou, X.; Luo, J.; Jin, D. Quercetin reduces neural tissue damage and promotes astrocyte activation after spinal cord injury in rats. J. Cell. Biochem., 2018, 119(2), 2298-2306.
[] [PMID: 28865131]
Li, J.; Wang, X.; Wang, Y.; Lu, C.; Zheng, D.; Zhang, J. Isoquercitrin, a flavonoid glucoside, exerts a positive effect on osteogenesis in vitro and in vivo. Chem. Biol. Interact., 2019, 297, 85-94.
[] [PMID: 30365939]
Tian, X.; Jiang, H.; Chen, Y.; Ao, X.; Chen, C.; Zhang, W.; He, F.; Liao, X.; Jiang, X.; Li, T.; Zhang, Z.; Zhang, X. Baicalein Accelerates Tendon-Bone Healing via Activation of Wnt/β-Catenin Signaling Pathway in Rats. BioMed. Res. Int., 2018, 2018, 3849760.
[] [PMID: 29693006]
Dai, J.; Qiu, Y.M.; Ma, Z.W.; Yan, G.F.; Zhou, J.; Li, S.Q.; Wu, H.; Jin, Y.C.; Zhang, X.H. Neuroprotective effect of baicalin on focal cerebral ischemia in rats. Neural Regen. Res., 2018, 13(12), 2129-2133.
[] [PMID: 30323141]
Kanji, S.; Das, H. Advances of stem cell therapeutics in cutaneous wound healing and regeneration. Mediators Inflamm., 2017, 2017, 5217967.
[] [PMID: 29213192]
Song, Y.; Guo, B.; Ma, S.; Chang, P.; Tao, K. Naringin suppresses the growth and motility of hypertrophic scar fibroblasts by inhibiting the kinase activity of Akt. Biomed. Pharmacother., 2018, 105, 1291-1298.
[] [PMID: 30021366]
Nday, C.M.; Eleftheriadou, D.; Jackson, G. Naringin nanoparticles against neurodegenerative processes: A preliminary work. Hell. J. Nucl. Med., 2019, 22(Suppl.), 32-41.
[PMID: 30877721]
Chen, S.; Deng, X.; Ma, K.; Zhao, L.; Huang, D.; Li, Z.; Shao, Z. Icariin improves the viability and function of cryopreserved human nucleus Pulposus-Derived mesenchymal stem cells. Oxid. Med. Cell. Longev., 2018, 2018, 3459612.
[] [PMID: 30050653]
Xu, S.J.; Zhang, F.; Wang, L.J.; Hao, M.H.; Yang, X.J.; Li, N.N.; Ji, H.L.; Xu, P. Flavonoids of Rosa roxburghii Tratt offers protection against radiation induced apoptosis and inflammation in mouse thymus. Apoptosis, 2018, 23(9-10), 470-483.
[] [PMID: 29995207]
Gong, M.; Chi, C.; Ye, J.; Liao, M.; Xie, W.; Wu, C.; Shi, R.; Zhang, L. Icariin-loaded electrospun PCL/gelatin nanofiber membrane as potential artificial periosteum. Colloids Surf. B Biointerfaces, 2018, 170(170), 201-209.
[] [PMID: 29909312]
Jangde, R.; Srivastava, S.; Singh, M.R.; Singh, D. In vitro and In vivo characterization of quercetin loaded multiphase hydrogel for wound healing application. Int. J. Biol. Macromol., 2018, 115, 1211-1217.
[] [PMID: 29730004]
Priprem, A.; Damrongrungruang, T.; Limsitthichaikoon, S.; Khampaenjiraroch, B.; Nukulkit, C.; Thapphasaraphong, S.; Limphirat, W. Topical niosome gel containing an anthocyanin complex: A potential oral wound healing in rats. AAPS PharmSciTech, 2018, 19(4), 1681-1692.
[] [PMID: 29532424]
Ahmed, O.M.; Mohamed, T.; Moustafa, H.; Hamdy, H.; Ahmed, R.R.; Aboud, E. Quercetin and low level laser therapy promote wound healing process in diabetic rats via structural reorganization and modulatory effects on inflammation and oxidative stress. Biomed. Pharmacother., 2018, 101, 58-73.
[] [PMID: 29477473]
Han, Y.; Wang, X.; Ma, D.; Wu, X.; Yang, P.; Zhang, J. Ipriflavone promotes proliferation and osteogenic differentiation of periodontal ligament cells by activating GPR30/PI3K/AKT signaling pathway. Drug Des. Devel. Ther., 2018, 12, 137-148.
[] [PMID: 29391778]
Asfour, M.H.; Elmotasem, H.; Mostafa, D.M.; Salama, A.A.A. Chitosan based Pickering emulsion as a promising approach for topical application of rutin in a solubilized form intended for wound healing: In vitro and in vivo study. Int. J. Pharm., 2017, 534(1-2), 325-338.
[] [PMID: 29074391]
Chu, C.; Deng, J.; Cao, C.; Man, Y.; Qu, Y. Evaluation of epigallocatechin-3-gallate modified collagen membrane and concerns on schwann cells. BioMed Res. Int., 2017, 2017, 9641801.
[] [PMID: 28894753]
Panche, A.N.; Diwan, A.D.; Chandra, S.R. Flavonoids: An overview. J. Nutr. Sci., 2016, 5-47.
[] [PMID: 28620474]
Ginwala, R.; Bhavsar, R.; Chigbu, D.I.; Jain, P.; Khan, Z.K. Potential role of flavonoids in treating chronic inflammatory diseases with a special focus on the anti-inflammatory activity of apigenin. Antioxidants, 2019, 8(2) E35.
[] [PMID: 30764536]
Aherne, SA N.M.; O'Brien, NM. Dietary flavonols: Chemistry, food content, and metabolism Nutrition, 2002, 18, 75e81.
Tsao, R. Chemistry and biochemistry of dietary polyphenols. Nutrients, 2010, 2, 1231-1246.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [1475 - 1488]
Pages: 14
DOI: 10.2174/1389557519666190617150051
Price: $65

Article Metrics

PDF: 48