Abstract
Background & Objective: Alzheimer’s disease (AD) and Parkinson’s disease (PD) affect an increasing number of the elderly population worldwide. The existing treatments mainly improve the core symptoms of AD and PD in a temporary manner and cause alarming side effects. Naturally occurring flavonoids are well-documented for neuroprotective and neurorestorative effects against various neurodegenerative diseases. Thus, we analyzed the pharmacokinetics of eight potent natural products flavonoids for the druggability and discussed the neuroprotective and neurorestorative effects and the underlying mechanisms.
Conclusion: This review provides valuable clues for the development of novel therapeutics against neurodegenerative diseases.
Keywords: Neurodegenerative diseases, flavonoids, neuroprotective, neurorestorative, pharmacological appraisal, pathogenesis.
Graphical Abstract
[1]
Erkkinen MG, Kim M-O, Geschwind MD. Clinical neurology and epidemiology of the major neurodegenerative diseases. Cold Spring Biol 2017; 13: 033118.
[2]
Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer disease. Nat Rev Neurol 2011; 7(3): 137-52.
[3]
Gopalakrishna A, Alexander SA. Understanding Parkinson disease: A complex and multifaceted illness. J Neurosci 2015; 47(6): 320-6.
[4]
Braak H, Del Tredici K. Potential pathways of abnormal tau and α-synuclein dissemination in sporadic Alzheimer’s and Parkinson’s Diseases. Cold Spring Biol 2016; 8(11): a023630.
[5]
Menzies FM, Fleming A, Caricasole A, et al. Autophagy and neurodegeneration: Pathogenic mechanisms and therapeutic opportunities. Neuron 2017; 93(5): 1015-34.
[6]
Heneka MT, Golenbock DT, Latz E. Innate immunity in Alzheimer’s disease. Nat Immunol 2015; 16(3): 229-36.
[7]
Hirtz D, Thurman D, Gwinn-Hardy K, Mohamed M, Chaudhuri A, Zalutsky R. How common are the “common” neurologic disorders? Neurology 2007; 68(5): 326-37.
[8]
Goedert M. Alzheimer’s and Parkinson’s diseases: The prion concept in relation to assembled A beta, tau, and alpha-synuclein. Science 2015; 349(6248)
[9]
Bassani TB, Vital MA, Rauh LK. Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs. Arquivos de Neuro 2015; 73(7): 616-23.
[10]
Cooper EL, Ma MJ. Alzheimer disease: Clues from traditional and complementary medicine. J Tradit Complement Med 2017; 7(4): 380-5.
[11]
Farahani MS, Bahramsoltani R, Farzaei MH, Abdollahi M, Rahimi R. Plant-derived natural medicines for the management of depression: An overview of mechanisms of action. Rev Neurosci 2015; 26(3): 305-21.
[12]
Gao J, Inagaki Y, Liu Y. Research progress on flavonoids isolated from traditional Chinese medicine in treatment of Alzheimer’s disease. Intractable Rare Dis Res 2013; 2(1): 3-10.
[14]
Francardo V, Schmitz Y, Sulzer D, Cenci MA. Neuroprotection and neurorestoration as experimental therapeutics for Parkinson's diseaseExp Neurol 2017; 298(Pt B): 137-47
[15]
Frandsen JR, Narayanasamy P. Neuroprotection through flavonoid: Enhancement of the glyoxalase pathway. Redox Biol 2018; 14: 465-73.
[16]
Orban-Gyapai O, Raghavan A, Vasas A, Forgo P, Hohmann J, Shah Z. Flavonoids isolated from rumex aquaticus exhibit neuroprotective and neurorestorative properties by enhancing neurite outgrowth and synaptophysin. CNS Neurol Disord Drug Targets 2014; 13(8): 1458-64.
[17]
Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement 2014; 10(2): e47-92.
[18]
Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement 2013; 9(2): 208-45.
[19]
Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement 2012; 8(2): 131-68.
[20]
Rosenberg RN, Lambracht-Washington D, Yu G, Xia W. Genomics of Alzheimer Disease: A review. JAMA Neurol 2016.
[21]
Wisniewski T, Goni F. Immunotherapeutic approaches for Alzheimer’s disease. Neuron 2015; 85(6): 1162-76.
[22]
Ahmed T, Javed S, Javed S, et al. Resveratrol and Alzheimer’s disease: Mechanistic insights. Mol Neurobiol 2017; 54(4): 2622-35.
[23]
Ankarcrona M, Winblad B, Monteiro C, et al. Current and future treatment of amyloid diseases. J Intern Med 2016; 280(2): 177-202.
[24]
Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 2016; 8(6): 595-608.
[25]
Giri M, Zhang M, Lü Y. Genes associated with Alzheimer’s disease: An overview and current status. Clin Interv Aging 2016; 11: 665-81.
[26]
Kanekiyo T, Xu H, Bu G. ApoE and Abeta in Alzheimer’s disease: accidental encounters or partners? Neuron 2014; 81(4): 740-54.
[27]
Rojas-Gutierrez E, Munoz-Arenas G, Trevino S, et al. Alzheimer’s disease and metabolic syndrome: A link from oxidative stress and inflammation to neurodegeneration. Synapse 2017.
[http://dx.doi.org/10.1002/ syn.21990]
[http://dx.doi.org/10.1002/ syn.21990]
[28]
Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: A review. JAMA 2014; 311(16): 1670-83.
[29]
Giasson BI, Lee VMY. Are ubiquitination pathways central to Parkinson’s disease? Cell 2003; 114(1): 1-8.
[30]
Michel PP, Hirsch EC, Hunot S. Understanding dopaminergic cell death pathways in parkinson disease. Neuron 2016; 90(4): 675-91.
[31]
Brundin P, Melki R. Prying into the prion hypothesis for Parkinson’s disease. J Neurosci 2017; 37(41): 9808-18.
[32]
Schapira AHV, Chiasserini D, Beccari T, Parnetti L. Glucocerebrosidase in Parkinson’s disease: Insights into pathogenesis and prospects for treatment. Mov Disord 2016; 31(6): 830-5.
[33]
Joshi N, Singh S. Updates on immunity and inflammation in Parkinson disease pathology. J Neurosci Res 2018; 96(3): 379-90.
[34]
Surmeier DJ, Obeso JA, Halliday GM. Parkinson’s disease is not simply a prion disorder. J Neurosci 2017; 37(41): 9799-807.
[35]
Roberson ED, Mucke L. 100 years and counting: Prospects for defeating Alzheimer’s disease. Science 2006; 314(5800): 781-4.
[36]
Hughes RE, Nikolic K, Ramsay RR. One for all? hitting multiple Alzheimer’s disease targets with one drug. Front Neurosci 2016; 25(10): 177.
[37]
Shoulson I. Experimental therapeutics of neurodegenerative disorders: Unmet needs. Science 1998; 282(5391): 1072-4.
[38]
Hickey P, Stacy M. Deep brain stimulation: a paradigm shifting approach to treat parkinson’s disease. Front Neurosci-Switz 2016; 10: 173.
[39]
Lotia M, Jankovic J. New and emerging medical therapies in Parkinson’s disease. Expert Opin Pharmacother 2016; 17(7): 895-909.
[40]
Oertel W, Schulz JB. Current and experimental treatments of Parkinson disease: A guide for neuroscientists. J Neurochem 2016; 139(1): 325-37.
[41]
Yacoubian TA, Standaert DG. Targets for neuroprotection in Parkinson’s disease. Biochimica Mol Dis 2009; 1792(7): 676-87.
[42]
Franco R, Cedazo-Minguez A. Successful therapies for Alzheimer’s disease: Why so many in animal models and none in humans? Front Pharmacol 2014; 25(5): 146.
[43]
Katsuno M, Tanaka F, Sobue G. Perspectives on molecular targeted therapies and clinical trials for neurodegenerative diseases. J Neurol Neurosurg Psychiatry 2012; 83(3): 329-35.
[44]
Barker-Haliski M, Friedman D, White HS, French JA. How clinical development can, and should, inform translational science. Neuron 2014; 84(3): 582-93.
[45]
Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 2004; 3(8): 711-5.
[46]
Eddershaw PJ, Beresford AP, Bayliss MK. ADME/PK as part of a rational approach to drug discovery. Drug Discov Today 2000; 5(9): 409-14.
[47]
Lin J, Sahakian DC, de Morais SMF, Xu JH, Polzer RJ, Winter SM. The role of absorption, distribution, metabolism, excretion and toxicity in drug discovery. Curr Top Med Chem 2003; 3(10): 1125-54.
[48]
Pires DE, Blundell TL, Ascher DB. pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J Med Chem 2015; 58(9): 4066-72.
[49]
Yates JWT, Arundel PA. On the volume of distribution at steady state and its relationship with two-compartmental models. J Pharm Sci 2008; 97(1): 111-22.
[50]
Preissner SC, Hoffmann MF, Preissner R, Dunkel M, Gewiess A, Preissner S. Polymorphic cytochrome P450 enzymes (CYPs) and their role in personalized therapy. PLoS One 2013; 8(12): e82562.
[51]
Tohge T, Fernie AR. Leveraging natural variance towards enhanced understanding of phytochemical sunscreens. Trends Plant Sci 2017; 22(4): 308-15.
[52]
Leyva-López N, Gutierrez-Grijalva E, Ambriz-Perez D, Heredia J. Flavonoids as cytokine modulators: A possible therapy for inflammation-related diseases. Int J Mol Sci 2016; 17(6): 921.
[53]
Gu Y, Chen JP, Shen JG. Herbal medicines for ischemic stroke: combating inflammation as therapeutic targets. J Neuroimmune Pharmacol 2014; 9(3): 313-39.
[54]
Corona G, Vauzour D. Neuroprotective effects of polyphenols in aging and age‐related neurological disorders. Neuroprotect Effect Phytochem Neurol Disord 2017; 65: 485-9.
[55]
Dal-Pan A, Dudonne S, Bourassa P, et al. Cognitive-enhancing effects of a polyphenols-rich extract from fruits without changes in neuropathology in an animal model of Alzheimer’s disease. J Alzheimers Dis 2017; 55(1): 115-35.
[56]
Commenges D, Scotet V, Renaud S, et al. Intake of flavonoids and risk of dementia. Eur J Epidemiol 2000; 16(4): 357-63.
[57]
Letenneur L, Proust-Lima C, Le Gouge A, Dartigues J-F, Barberger-Gateau P. Flavonoid intake and cognitive decline over a 10-year period. Am J Epidemiol 2007; 165(12): 1364-71.
[58]
Maher P. Protective effects of fisetin and other berry flavonoids in Parkinson’s disease. Food Funct 2017; 8(9): 3033-42.
[59]
Darvesh AS, McClure M, Sadana P, et al. Neuroprotective properties of dietary polyphenols in Parkinson’s disease. Neuroprotect Effect Phytochem Neurol Disord 2017; 16: 243.
[60]
Ali F. Rahul, Naz F, Jyoti S, Siddique YH. Health functionality of apigenin: A review. Int J Food Prop 2017; 20(6): 1197-238.
[61]
Zhao L, Wang J-L, Wang Y-R, Fa X-Z. Apigenin attenuates copper-mediated β-amyloid neurotoxicity through antioxidation, mitochondrion protection and MAPK signal inactivation in an AD cell model. Brain Res 2013; 1492: 33-45.
[62]
Balez R, Steiner N, Engel M, et al. Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease. Sci Rep 2016; 6: 31450.
[63]
Liu R, Zhang TT, Yang HG, Lan X, Ying JA, Du GH. The flavonoid apigenin protects brain neurovascular coupling against amyloid-beta(25-35)-induced toxicity in mice. J Alzheimers Dis 2011; 24(1): 85-100.
[64]
Liang H, Sonego S, Gyengesi E, et al. Anti-Inflammatory and neuroprotective effect of apigenin: Studies in the GFAP-IL6 mouse model of chronic neuroinflammation. Free Radic Med 2017; 108: S10.
[65]
Liu WH, Kong SZ, Xie QF, et al. Protective effects of apigenin against 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells. Int J Mol Med 2015; 35(3): 739-46.
[66]
Anusha C, Sumathi T, Joseph LD. Protective role of apigenin on rotenone induced rat model of Parkinson’s disease: Suppression of neuroinflammation and oxidative stress mediated apoptosis. Chem Biol Interact 2017; 269: 67-79.
[67]
Patil SP, Jain PD, Sancheti JS, Ghumatkar PJ, Tambe R, Sathaye S. Neuroprotective and neurotrophic effects of Apigenin and Luteolin in MPTP induced parkinsonism in mice. Neuropharmacology 2014; 86: 192-202.
[68]
Siddique YH, Jyoti S. Alteration in biochemical parameters in the brain of transgenic Drosophila melanogaster model of Parkinson’s disease exposed to apigenin. Integr Med Res 2017; 6(3): 245-53.
[69]
Singh NA, Mandal AKA, Khan ZA. Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG). Nutr J 2016; 15(1): 60.
[70]
Chakrawarti L, Agrawal R, Dang S, Gupta S, Gabrani R. Therapeutic effects of EGCG: A patent review. Expert Opin Ther Pat 2016; 26(8): 907-16.
[71]
Singh NA, Mandal AK, Khan ZA. Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG). Nutr J 2016; 15(1): 60.
[72]
Zhang ZX, Li YB, Zhao RP. Epigallocatechin gallate attenuates beta-amyloid generation and oxidative stress involvement of PPARgamma in N2a/APP695 cells. Neurochem Res 2017; 42(2): 468-80.
[73]
Cheng WJ, Huang HC, Chen WJ, Huang CN, Peng CH, Lin CL. Epigallocatechin gallate attenuates amyloid beta-induced inflammation and neurotoxicity in EOC 13.31 microglia. Eur J Pharmacol 2016; 770: 16-24.
[74]
Wobst HJ, Sharma A, Diamond MI, Wanker EE, Bieschke J. The green tea polyphenol (-)-epigallocatechin gallate prevents the aggregation of tau protein into toxic oligomers at substoichiometric ratios. FEBS Lett 2015; 589(1): 77-83.
[75]
Choi SM, Kim BC, Cho YH, et al. Effects of flavonoid compounds on beta-amyloid-peptide-induced neuronal death in cultured mouse cortical neurons. Chonnam Med J 2014; 50(2): 45-51.
[76]
Jia N, Han K, Kong JJ, et al. Epigallocatechin-3-gallate alleviates spatial memory impairment in APP/PS1 mice by restoring IRS-1 signaling defects in the hippocampus. Mol Cell Biochem 2013; 380(1-2): 211-8.
[77]
Zhao J, Xu L, Liang Q, et al. Metal chelator EGCG attenuates Fe(III)-induced conformational transition of alpha-synuclein and protects AS-PC12 cells against Fe(III)-induced death. J Neurochem 2017; 143(1): 136-46.
[78]
Lorenzen N, Nielsen SB, Yoshimura Y, et al. How epigallocatechin gallate can inhibit alpha-synuclein oligomer toxicity in vitro. J Biol Chem 2014; 289(31): 21299-310.
[79]
Xu Y, Zhang Y, Quan Z, et al. Epigallocatechin gallate (EGCG) inhibits alpha-synuclein aggregation: A potential agent for parkinson’s disease. Neurochem Res 2016; 41(10): 2788-96.
[80]
Ye Q, Ye L, Xu X, et al. Epigallocatechin-3-gallate suppresses 1-methyl-4-phenyl-pyridine-induced oxidative stress in PC12 cells via the SIRT1/PGC-1alpha signaling pathway. BMC Complement Altern Med 2012; 12: 82.
[81]
Xu Q, Langley M, Kanthasamy AG, Reddy MB. Epigallocatechin gallate has a neurorescue effect in a mouse model of Parkinson disease. J Nutr 2017; 147(10): 1926-31.
[82]
Ma XL, Lv JW, Sun XL, et al. Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone. Sci Rep 2016; 6: 24562.
[83]
Sachdeva AK, Kuhad A, Chopra K. Naringin ameliorates memory deficits in experimental paradigm of Alzheimer’s disease by attenuating mitochondrial dysfunction. Pharmacol Biochem Behav 2014; 127: 101-10.
[84]
Wang D, Gao K, Li X, et al. Long-term naringin consumption reverses a glucose uptake defect and improves cognitive deficits in a mouse model of Alzheimer’s disease. Pharmacol Biochem Behav 2012; 102(1): 13-20.
[85]
Kim HD, Jeong KH, Jung UJ, Kim SR. Naringin treatment induces neuroprotective effects in a mouse model of Parkinson’s disease in vivo, but not enough to restore the lesioned dopaminergic system. J Nutr Biochem 2016; 28: 140-6.
[86]
Jung UJ, Leem E, Kim SR. Naringin: A protector of the nigrostriatal dopaminergic projection. Exp Neurobiol 2014; 23(2): 124-9.
[87]
Leem E, Nam JH, Jeon MT, et al. Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson’s disease. J Nutr Biochem 2014; 25(7): 801-6.
[88]
Jung UJ, Kim SR. Effects of naringin, a flavanone glycoside in grapefruits and citrus fruits, on the nigrostriatal dopaminergic projection in the adult brain. Neural Regen Res 2014; 9(16): 1514-7.
[89]
Zhao J, Luo D, Liang Z, Lao L, Rong J. Plant natural product puerarin ameliorates depressive behaviors and chronic pain in mice with spared nerve injury (SNI). Mol Neurobiol 2017; 54(4): 2801-12.
[90]
Li L, Xue Z, Chen L, Chen X, Wang H, Wang X. Puerarin suppression of Aβ 1–42-induced primary cortical neuron death is largely dependent on ERβ. Brain Res 2017; 1657: 87-94.
[91]
Zhou Y, Xie N, Li L. Puerarin alleviates cognitive impairment and oxidative stress in APP/PS1 transgenic mice. Int J Neuropsychopharmacol 2014; 17(4): 635-44.
[92]
Yao Y, Chen X, Bao Y, Wu Y. Puerarin inhibits betaamyloid peptide 142induced tau hyperphosphorylation via the Wnt/betacatenin signaling pathway. Mol Med Rep 2017; 16(6): 9081-5.
[93]
Wu L, Tong T, Wan S, et al. Protective effects of puerarin against abeta 1-42-induced learning and memory impairments in mice. Planta Med 2017; 83(3-4): 224-31.
[94]
Zhao SS, Yang WN, Jin H, Ma KG, Feng GF. Puerarin attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice. Neurotoxicology 2015; 51: 166-71.
[95]
Zhang H, Liu Y, Lao M, Ma Z, Yi X. Puerarin protects Alzheimer’s disease neuronal cybrids from oxidant-stress induced apoptosis by inhibiting pro-death signaling pathways. Exp Gerontol 2011; 46(1): 30-7.
[96]
Lu XL, Liu JX, Wu Q, et al. Protective effects of puerarin against Ass40-induced vascular dysfunction in zebrafish and human endothelial cells. Eur J Pharmacol 2014; 732: 76-85.
[97]
Zhao J, Cheng YY, Fan W, et al. Botanical drug puerarin coordinates with nerve growth factor in the regulation of neuronal survival and neuritogenesis via activating ERK1/2 and PI3K/Akt signaling pathways in the neurite extension process. CNS Neurosci Ther 2015; 21(1): 61-70.
[98]
Jiang M, Yun Q, Niu G, Gao Y, Shi F, Yu S. Puerarin prevents inflammation and apoptosis in the neurocytes of a murine Parkinson’s disease model. Genet Mol Res 2016; 15(4): 385.
[99]
Cheng Y, Leng W, Zhang J. Protective effect of puerarin against oxidative stress injury of neural cells and related mechanisms. Med Sci Monit 2016; 22: 1244-9.
[100]
Zhao J, Cheng Y, Yang C, et al. Botanical drug puerarin attenuates 6-Hydroxydopamine (6-OHDA)-induced neurotoxicity via upregulating mitochondrial enzyme arginase-2. Mol Neurobiol 2016; 53(4): 2200-11.
[101]
Zhu G, Wang X, Wu S, Li X, Li Q. Neuroprotective effects of puerarin on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced Parkinson’s disease model in mice. Phytother Res 2014; 28(2): 179-86.
[102]
Zhang X, Xiong J, Liu S, et al. Puerarin protects dopaminergic neurons in Parkinson’s disease models. Neuroscience 2014; 280: 88-98.
[103]
Zheng Q-H, Li X-L, Mei Z-G, et al. Efficacy and safety of puerarin injection in curing acute ischemic stroke: A meta-analysis of randomized controlled trials. Medicine 2017; 96(1): e5803.
[104]
Yuan M, Liu G, Zheng X, et al. Effects of puerarin combined with conventional therapy on ischemic stroke. Exp Ther Med 2017; 14(4): 2943-6.
[105]
Xiao B-X, Feng L, Cao F-R, et al. Pharmacokinetic profiles of the five isoflavonoids from Pueraria lobata roots in the CSF and plasma of rats. J Ethnopharmacol 2016; 184: 22-9.
[106]
Ossola B, Kääriäinen TM, Männistö PT. The multiple faces of quercetin in neuroprotection. Expert Opin Drug Saf 2009; 8(4): 397-409.
[107]
Kumar M, Kasala ER, Bodduluru LN, Kumar V, Lahkar M. Molecular and biochemical evidence on the protective effects of quercetin in isoproterenol‐induced acute myocardial injury in rats. J Biochem Mol Toxicol 2017; 31(1): 1-8.
[108]
Lin X, Lin C-H, Zhao T, et al. Quercetin protects against heat stroke-induced myocardial injury in male rats: Antioxidative and antiinflammatory mechanisms. Chem Biol Interact 2017; 265: 47-54.
[109]
Jing Z, Wang Z, Li X, et al. Protective effect of quercetin on posttraumatic cardiac injury. Sci Rep 2016; 6: 30812.
[110]
Le HN, Shin SA, Choo GS, et al. Anti-inflammatory effect of quercetin and galangin in LPS-stimulated RAW264.7 macrophages and DNCB-induced atopic dermatitis animal models. Int J Mol Med 2018; 41(2): 888-98.
[111]
Godoy JA, Lindsay CB, Quintanilla RA, Carvajal FJ, Cerpa W, Inestrosa NC. Quercetin exerts differential neuroprotective effects against H2O2 and Aβ aggregates in hippocampal neurons: The role of mitochondria. Mol Neurobiol 2017; 54(9): 7116-28.
[112]
Lee M, McGeer EG, McGeer PL. Quercetin, not caffeine, is a major neuroprotective component in coffee. Neurobiol Aging 2016; 46: 113-23.
[113]
Ansari MA, Abdul HM, Joshi G, Opii WO, Butterfield DA. Protective effect of quercetin in primary neurons against Aβ (1–42): Relevance to Alzheimer’s disease. J Nutr Biochem 2009; 20(4): 269-75.
[114]
Wang DM, Li SQ, Wu WL, Zhu XY, Wang Y, Yuan HY. Effects of long-term treatment with quercetin on cognition and mitochondrial function in a mouse model of Alzheimer’s disease. Neurochem Res 2014; 39(8): 1533-43.
[115]
Kumar H, Lim H-W, More SV, et al. The role of free radicals in the aging brain and Parkinson’s disease: Convergence and parallelism. Int J Mol Sci 2012; 13(8): 10478-504.
[116]
Sarrafchi A, Bahmani M, Shirzad H, Rafieian-Kopaei M. Oxidative stress and Parkinson’s disease: New hopes in treatment with herbal antioxidants. Curr Pharm Des 2016; 22(2): 238-46.
[117]
Karuppagounder S, Madathil S, Pandey M, Haobam R, Rajamma U, Mohanakumar K. Quercetin up-regulates mitochondrial complex-I activity to protect against programmed cell death in rotenone model of Parkinson’s disease in rats. Neuroscience 2013; 236: 136-48.
[118]
Ahn TB, Jeon BS. The role of quercetin on the survival of neuron-like PC12 cells and the expression of alpha-synuclein. Neural Regen Res 2015; 10(7): 1113-9.
[119]
Chen L, Sun L, Liu Z, Wang H, Xu C. Protection afforded by quercetin against H2O2-induced apoptosis on PC12 cells via activating PI3K/Akt signal pathway. J Recept Signal Transduct Res 2016; 36(1): 98-102.
[120]
Li DW, Sun JY, Wang K, et al. Attenuation of cisplatin-induced neurotoxicity by cyanidin, a natural inhibitor of ros-mediated apoptosis in PC12 cells. Cell Mol Neurobiol 2015; 35(7): 995-1001.
[121]
Song N, Zhang L, Chen W, et al. Cyanidin 3-O-β-glucopyranoside activates peroxisome proliferator-activated receptor-γ and alleviates cognitive impairment in the APPswe/PS1ΔE9 mouse model. Biochimica et Biophysica Acta Mol Dis 2016; 1862(9): 1786-800.
[122]
Winter AN, Ross EK, Khatter S, Miller K, Linseman DA. Chemical basis for the disparate neuroprotective effects of the anthocyanins, callistephin and kuromanin, against nitrosative stress. Free Radic Biol Med 2017; 103: 23-34.
[123]
Moore K, MacSween M, Shoichet M. Immobilized concentration gradients of neurotrophic factors guide neurite outgrowth of primary neurons in macroporous scaffolds. Tissue Eng 2006; 12(2): 267-78.
[124]
Han MH, Lee EH, Koh SH. Current opinion on the role of neurogenesis in the therapeutic strategies for Alzheimer disease, parkinson disease, and ischemic stroke; considering neuronal voiding function. Int Neurourol J 2016; 20(4): 276-87.
[125]
Ortiz-Lopez L, Marquez-Valadez B, Gomez-Sanchez A, et al. Green tea compound epigallo-catechin-3-gallate (EGCG) increases neuronal survival in adult hippocampal neurogenesis in vivo and in vitro. Neuroscience 2016; 322: 208-20.
[126]
Seong KJ, Lee HG, Kook MS, Ko HM, Jung JY, Kim WJ. Epigallocatechin-3-gallate rescues LPS-impaired adult hippocampal neurogenesis through suppressing the TLR4-NF-kappaB signaling pathway in mice. Korean J Physiol Pharmacol 2016; 20(1): 41-51.
[127]
Wang Y, Li M, Xu X, Song M, Tao H, Bai Y. Green tea epigallocatechin-3-gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis. Mol Nutr Food Res 2012; 56(8): 1292-303.
[128]
Nabavi SF, Braidy N, Gortzi O, et al. Luteolin as an anti-inflammatory and neuroprotective agent: A brief review Brain Res Bull 2015; 119(Pt A): 1-11
[129]
Nishina A, Kimura H, Tsukagoshi H, et al. Neurite outgrowth in PC12 cells stimulated by components from dendranthema x grandiflorum cv. “Mottenohoka” is enhanced by suppressing phosphorylation of p38MAPK. Evid Based Complement Alternat Med 2013; 2013: 403503.
[130]
Chen PY, Wu MJ, Chang HY, Tai MH, Ho CT, Yen JH. Up-regulation of miR-34a expression in response to the luteolin-induced neurite outgrowth of PC12 cells. J Agric Food Chem 2015; 63(16): 4148-59.
[131]
Lin LF, Chiu SP, Wu MJ, Chen PY, Yen JH. Luteolin induces microRNA-132 expression and modulates neurite outgrowth in PC12 cells. PLoS One 2012; 7(8): e43304.
[132]
Lin CW, Wu MJ, Liu IY-C, Su JD, Yen JH. Neurotrophic and cytoprotective action of luteolin in PC12 cells through ERK-dependent induction of Nrf2-driven HO-1 expression. J Agric Food Chem 2010; 58(7): 4477-86.
[133]
El Omri A, Han J, Kawada K, Ben Abdrabbah M, Isoda H. Luteolin enhances cholinergic activities in PC12 cells through ERK1/2 and PI3K/Akt pathways. Brain Res 2012; 1437: 16-25.
[134]
Zhou YX, Zhang H, Peng C. Puerarin: A review of pharmacological effects. Phytother Res 2014; 28(7): 961-75.
[135]
Wei SY, Chen Y, Xu XY. Progress on the pharmacological research of puerarin: A review. Chin J Nat Med 2014; 12(6): 407-14.
[136]
Li L, Xue Z, Chen L, Chen X, Wang H, Wang X. Puerarin suppression of Abeta1-42-induced primary cortical neuron death is largely dependent on ERbeta. Brain Res 2017; 1657: 87-94.
[137]
Hong XP, Chen T, Yin NN, et al. Puerarin ameliorates D-Galactose induced enhanced hippocampal neurogenesis and tau hyperphosphorylation in rat brain. J Alzheimers Dis 2016; 51(2): 605.
[138]
Haque Bhuiyan MM, Mohibbullah M, Hannan MA, et al. The neuritogenic and synaptogenic effects of the ethanolic extract of radix Puerariae in cultured rat hippocampal neurons. J Ethnopharmacol 2015; 173: 172-82.
[139]
Suganthy N, Devi KP, Nabavi SF, Braidy N, Nabavi SM. Bioactive effects of quercetin in the central nervous system: Focusing on the mechanisms of actions. Biomed Pharmacother 2016; 84: 892-908.
[140]
Tchantchou F, Lacor PN, Cao Z, et al. Stimulation of neurogenesis and synaptogenesis by bilobalide and quercetin via common final pathway in hippocampal neurons. J Alzheimers Dis 2009; 18(4): 787-98.
[141]
Tangsaengvit N, Kitphati W, Tadtong S, Bunyapraphatsara N, Nukoolkarn V. Neurite outgrowth and neuroprotective effects of quercetin from Caesalpinia mimosoides Lamk. on cultured P19-derived neurons. Evid Comp Alt Med 2013; 2013: 838051.
[142]
Ming-Ming C, Zhi-Qi Y. ZHANG LY, Hong L. Quercetin promotes neurite growth through enhancing intracellular cAMP level and GAP-43 expression. J Nat Med 2015; 13(9): 667-72.
[143]
Nakajima KI, Niisato N, Marunaka Y. Quercetin stimulates NGF-induced neurite outgrowth in PC12 cells via activation of Na+/K+/2Cl-cotransporter. Cell Physiol Biochem 2011; 28(1): 147-56.
[144]
Moosavi F, Hosseini R, Saso L, Firuzi O. Modulation of neurotrophic signaling pathways by polyphenols. Drug Des Devel Ther 2016; 10: 23-42.
[145]
Palazzolo G, Horvath P, Zenobi-Wong M. The flavonoid isoquercitrin promotes neurite elongation by reducing RhoA activity. PLoS One 2012; 7(11): e49979.
[146]
Rong JH, Tilton R, Shen JG, et al. Genome-wide biological response fingerprinting (BioReF) of the Chinese botanical formulation ISF-1 enables the selection of multiple marker genes as a potential metric for quality control. J Ethnopharmacol 2007; 113(1): 35-44.
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Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
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Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
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Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
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