Pharmacological Actions of Phytoconstituents on Neurodegenerative Disorders

doi.org/10.26538/tjnpr/v6i7.2

Authors

  • Abolanle A. A. Kayode Department of Biochemistry, School of Basic Medical Sciences, Babcock University, Ilishan-Remo, Ogun State, Nigeria
  • Omowumi T. Kayode Department of Biochemistry, College of Basic and Applied Sciences, Mountain Top University, Kilometer 12, Lagos-Ibadan Expressway, Prayer City, Ogun State, Nigeria
  • Damilare E. Rotimi Department of Biochemistry, College of Pure & Applied Sciences, Landmark University, Omu-Aran, Kwara State, Nigeria

Keywords:

resveratrol, curcumin, phytochemicals, pharmacological agents, Neurodegenerative disease

Abstract

Neurodegenerative diseases (NDs) have over the years become a growing cause for concern and it is increasingly becoming a major health problem associated with impairment, ageing of the brain and other neuropathological conditions. These include Parkinson’s isease, Dementia, Huntington’s disease, Alzheimer disease, and Depression. Due to increase in prevalence of various NDs over the years, there is growing need to provide suitable means by which the disease can be mitigated. Various pharmacological agents are being researched on to investigate the most suitable and effective means to curb these diseases. This review was aimed at perusing
therapeutic potentials of various pharmacological agents in the treatment of NDs. Over a hundred research papers, from Pubmed, NCBI, BMC med, Neurosci etc published on NDs treatments via phytochemicals within the past two decades were analysed. This review will help guide research on pharmacological agents with a wider range treatment options for NDs. Curcumins were most frequently studied for all NDs management. Other commonly used pharmacological agents are resveratrol, epigallocatechin n-gallate (ECGC) and l-theanine. In the management of NDs, curcumin is found to normalize altered mechanisms associated with caspase-3 level, TNF-α, COX-2, NO, iNOS, PGE2, IL-6, Glial fibrillary acidic protein (GFAP), IL-1β, insulin-degrading enzymes, apoptosis, inflammation, mitochondria dysfunction, inhibitory activity of AChE, and cell viability. It was surmised from the study that curcumin, resveratrol, ECGC and L-theanine are the most common and effective classes of phytochemicals for a wide range of NDs management. 

References

Youdim KA and Joseph JA. A Possible Emerging Role of Phytochemicals in Improving Age-Related Neurological Dysfunctions: A Multiplicity of Effects. Free Rad Biol Med. 2001; 30:583–594.

Kolominsky-Rabas PL, Sarti C, Heuschmann PU, Graf C, Siemonsen S, Neundoerfer B, Katalinic A, Lang E, Gassmann KG, von Stockert TR. A prospective community based study of stroke in Germany. The Erlangen Stroke Project (ESPro): Incidence and case fatality at 1, 3, and 12

months. Stroke. 1998; 29:2501-2506.

Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger Gateau P, Dartigues JF. Intake of flavonoids and risk of dementia. Eur J Epidemiol. 2000; 6:357-363.

Kumar V. Potential medicinal plants for CNS disorders: An overview. Phytother Res. 2006; 20:1023-1035.

Lee J, Jo DG, Park D, Chung HY, Mattson MP. Adaptive cellular stress pathways as therapeutic targets of dietary phytochemicals: focus on the nervous system. Pharmacol Rev. 2014; 66:815–868.

Mattson MP, Son TG, Camandola S. Viewpoint: Mechanisms of action and therapeutic potential of neurohormetic phytochemicals. Dose-Response. 2007; 5:174-186.

Slavin JL and Lloyd B. Health benefits of fruits and vegetables. Adv Nutr. 2012; 3:506-516.

Selvam AB. Inventory of Vegetable Crude Drug samples housed in Botanical Survey of India, Howrah. Pharmacogn Rev. 2008; 2:61-94.

Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev. 2010; 4:118-126.

Gopalakrishna A and Alexander SA. Understanding Parkinson disease: a complex and multifaceted illness. J Neurosci Nurs. 2015; 47:320-326.

Moon HE and Paek SH. Mitochondrial dysfunction in Parkinson’s disease. Exp Neurobiol. 2015; 24:103-116.

Bassani TB, Vital MA, Rauh LK. Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs. Arq Neuropsiquiatr. 2015; 73:616–623.

Qualls Z, Brown D, Ramlochansingh C, Hurley LL, Tizabi Y. Protective effects of curcumin against rotenone and salsolinol-induced toxicity: implications for Parkinson's disease. Neurotox Res. 2014; 25:81-89.

Le Douaron G, Schmidt F, Amar M, Kadar H, Debortoli L, Latini A., Séon-Méniel B, Ferrié L, Michel, PP, Touboul, D, Brunelle, A, Raisman-Vozari R, Figadère B. Neuroprotective effects of a brain permeant 6- aminoquinoxaline derivative in cell culture conditions that model the loss of dopaminergic neurons in Parkinson disease. Eur J Med Chem. 2015; 89:467-479.

Orme RP, Bhangal MS, Fricker RA. Calcitriol imparts neuroprotection in vitro to midbrain dopaminergic neurons by upregulating GDNF expression. PLoS ONE. 2013; 8:e62040.

Blesa J, Trigo-Damas I, Quiroga-Varela A, Jackson-Lewis VR. Oxidative stress and Parkinson’s disease. Front Neuroanat. 2015; 9:91.

Agim ZS and Cannon JR. Dietary factors in the etiology of Parkinson’s disease. BioMed Res Int. 2015. Retrieved from: https://doi.org/10.1155/2015/672838 (Accessed March 3rd, 2021).

Cheung ZH and Ip NY. The emerging role of autophagy in Parkinson’s disease. Mol Brain. 2009; 2:29.

Ren P, Jiang H, Li R, Wang J, Song N, Xu HM, Xie JX. Rosmarinic acid inhibits 6-OHDA-induced neurotoxicity by anti-oxidation in MES23.5 cells. J Mol Neurosci. 2009; 39:220–225.

Shahpiri Z, Bahramsoltani R, Farzaei MH Farzaei F, Rahimi R. Phytochemicals as future drugs for Parkinson’s disease: a comprehensive review. Rev Neurosci. 2016. Retrieved from: https://doi.org/10.1515/revneuro-2016- 0004 (Accessed March 6th, 2021).

Chao J, Yu MS, Ho YS, Wang M, Chang RC. Dietary oxyresveratrol prevents parkinsonian mimetic 6- hydroxydopamine neurotoxicity. Free Radic Biol Med. 2008; 45:1019–1026.

Kumar H, Kim IS, More SV, Kim BW, Bahk YY, Choi DK. Gastrodin protects apoptotic dopaminergic neurons in a toxin-induced Parkinson’s disease model. Evid-Based Compl Altern Med. 2013; 514095:13.

Du T, Li L, Song N, Xie J, Jiang H. Rosmarinic acid antagonized 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in MES23.5 dopaminergic cells. Int J Toxicol. 2010; 29:625–633.

Ham A, Lee HJ, Hong SS, Lee D, Mar W. Moracenin D from Mori cortex radicis protects SH-SY5Y cells against dopamine-induced cell death by regulating nurr1 and α- synuclein expression. Phytother Res. 2012; 26:620–624.

Kim KH, Song K, Yoon SH, Shehzad O, Kim YS, Son JH. Rescue of PINK1 protein null-specific mitochondrial complex IV deficits by ginsenoside reactivation of nitric oxide signaling. J Biol Chem. 2012; 287:44109–44120.

Elyasi L, Eftekhar-Vaghefi SH, Esmaeili-Mahani S. Morphine protects SH-SY5Y human neuroblastoma cells against 6-hydroxydopamine-induced cell damage: involvement of anti-oxidant, calcium blocking, and antiapoptotic properties. Rejuvenation Res. 2014; 17:255-263.

Li BY, Yuan YH, Hu JF, Zhao Q, Zhang DM, Chen NH. Protective effect of Bu-7, a flavonoid extracted from Clausena lansium, against rotenone injury in PC12 cells. Acta Pharmacol Sin. 2011; 32:1321-1326.

Tai KK and Truong DD. (-)-Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, reduces dichlorodiphenyltrichloroethane (DDT)-induced cell death in dopaminergic SHSY-5Y cells. Neurosci Lett. 2010; 482:183-187.

Tamilselvam K, Braidy N, Manivasagam T, Essa MM, Prasad NR, Karthikeyan S, Thenmozhi AJ, Selvaraju S, Guillemin GJ. Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson’s disease. Oxid

Med Cell Longev. 2013; 2013: 102741.

Filomeni G, Graziani I, De Zio D, Dini L, Centonze D, Rotilio G, Ciriolo MR. Neuroprotection of kaempferol by autophagy in models of rotenone-mediated acute toxicity: possible implications for Parkinson’s disease. Neurobiol Aging. 2012; 33:767–785.

Lee Y, Park HR Chun HJ, Lee J. Silibinin prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease via mitochondrial stabilization. J Neurosci Res. 2015; 93:755-765.

Park G, Kim HG, Ju MS, Ha SK, Park Y, Kim SY, Oh MS. 6-Shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson’s disease models via anti-neuroinflammation. Acta Pharmacol Sin. 2013; 34:1131-1139.

Leal LKAM, Júnior HVN, Cunha GMA, Moraes MO, Pessoa C, Oliveira RA, Silveira ER, Canuto KM, Viana,GSB. Amburoside A, a glucoside from Amburana cearensis, protects mesencephalic cells against 6- hydroxydopamineinduced neurotoxicity. Neurosci Lett. 2005; 388:86–90.

Wang XJ and Xu JX. Salvianic acid A protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity. Neurosci Res. 2005; 51:129-138.

Chao J, Yu MS, Ho YS, Wang M, Chang RC. Dietary oxyresveratrol prevents parkinsonian mimetic 6- hydroxydopamine neurotoxicity. Free Radic Biol Med. 2008; 45:1019-1026.

Chen JH, Ou HP, Lin CY, Lin FJ, Wu CR, Chang SW, Tsai CW. Carnosic acid prevents 6-hydroxydopamineinduced cell death in SH-SY5Y cells via mediation of glutathione synthesis. Chem Res Toxicol. 2012; 25:1893-1901.

Mendiola-Precoma J, Berumen LC, Padilla K, GarciaAlcocer G. Therapies for Prevention and Treatment of Alzheimer's Disease. Biomed Res Int. 2016; 2016:2589276.

Edwards Iii GA, Gamez N, Escobedo G Jr, Calderon O, Moreno-Gonzalez I. Modifiable Risk Factors for Alzheimer's Disease. Front Aging Neurosci. 2019; 11:146.

Raz L, Knoefel J, Bhaskar K. The neuropathology and cerebrovascular mechanisms of dementia. J Cereb Blood Flow Metab. 2016; 36:172-186.

Libro R, Giacoppo S, Soundara Rajan T, Bramanti P, Mazzon E. Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview. Mol. 2016; 21(4):518.

Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2011; 1:a006189.

Teixeira JP, de Castro AA, Soares FV, da Cunha EFF, Ramalho TC. Future Therapeutic Perspectives into the Alzheimer's Disease Targeting the Oxidative Stress Hypothesis. Mol. 2019; 24:4410.

Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol. 2013; 11:315-335.

Olivares D, Deshpande VK, Shi Y, Lahiri DK, Greig NH, Rogers JT, Huang X. N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for Alzheimer's disease, vascular dementia and Parkinson's disease. Curr Alzheimer Res. 2012; 9:746-758.

Liu J, Chang L, Song Y, Li H, Wu, Y. The role of NMDA receptors in Alzheimer's disease. Front Neurisci. 2019; 13:1-22.

Kuang H, Zhou ZF, Zhu YG, Wan, ZK, Yang, MW, Hong, FF, Yang, SL. Pharmacological Treatment of Vascular Dementia: A Molecular Mechanism Perspective. Aging Dis. 2021; 12:308-326.

Lastra G, Syed S, Kurukulasuriya LR, Manrique C, Sowers JR. Type 2 diabetes mellitus and hypertension: an update. Endocrinol Metab Clin North Am. 2014; 43:103-122.

Baba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VM, Trojanowski JQ, Iwatsubo T. Aggregation of alphasynuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am J Pathol. 1998; 152:879-884.

Orme T, Guerreiro R, Bras J. The Genetics of Dementia with Lewy Bodies: Current Understanding and Future Directions. Curr Neurol Neurosci Rep. 2018; 18:67.

Zhang G, Xia Y, Wan F, Ma, K, Guo X, Kou L, Yin S, Han C, Liu L, Huang J, Xiong N, Wang, T. New Perspectives on Roles of Alpha-Synuclein in Parkinson's Disease. Front Aging Neurosci. 2018; 10:370.

Jicha GA and Nelson PT. Management of frontotemporal dementia: targeting symptom management in such a heterogeneous disease requires a wide range of therapeutic options. Neurodegener Dis Manag. 2011; 1:141-156.

Libro R, Giacoppo S, Soundara Rajan T, Bramanti P, Mazzon E. Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview. Mol. 2016; 21:518.

Jin CY, Lee JD, Park C, Choi YH, Kim GY. Curcumin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated BV2 microglia. Acta Pharmacol Sin. 2007; 28:1645–1651.

Durairajan SSK, Liu LF, Lu JH, Chen LL, Yuan Q, Chung SK, Huang L, Li XS, Huang JD, Li M. Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer’s disease transgenic mouse model. Neurobiol Aging. 2012; 33:2903–2919.

Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse. J Neurosci. 2001; 21:8370–8377.

Wang Z, Xiong L, Wan W, Duan L, Bai X, Zu H. Intranasal BMP9 Ameliorates Alzheimer Disease-Like Pathology and Cognitive Deficits in APP/PS1 Transgenic Mice. Front Mol Neurosci. 2017; 10:1-14.

Debprasad C, Hemanta M, Paromita B, Durbadal O, Kumar KA, Shanta D, Kumar HP, Tapan C, Ashoke S, Sekhar C. Inhibition of NO(2), PGE(2), TNF-α, and iNOS EXpression by Shorea robusta L.: An Ethnomedicine Used for AntiInflammatory and Analgesic Activity. Evid-Based Compl ltern Med. 2012; 2012:254849.

Jang JH and Surh YJ. Protective effect of resveratrol on beta-amyloid-induced oxidative PC12 cell death. Free Radic Biol Med. 2003; 34:1100-1110.

Mokni M, Elkahoui S, Limam F, Amri M, Aouani E. Effect of resveratrol on antioxidant enzyme activities in the brain of healthy rat. Neurochem Res., 2007; 32:981-987.

Porquet D, Griñán-Ferré C, Ferrer I, Camins A, Sanfeliu C, del Valle J, Pallàs M. Neuroprotective role of transresveratrol in a murine model of familial Alzheimer’s disease. J Alzheimers Dis. 2014; 42:1209-1220.

Lonze BE and Ginty DD. Function and Regulation of CREB Family Transcription Factors in the Nervous System. Neuron. 2002; 35:605-623.

Kim SJ, Jeong HJ, Lee KM, Myung NY, An NH, Yang WM, Park SK, Lee HJ, Hong SH, Kim HM. Epigallocatechin-3-gallate suppresses NF-kappaB activation and phosphorylation of p38 MAPK and JNK in human astrocytoma U373MG cells. J Nutr Biochem., 2007; 18:587–596.

Biasibetti R, Tramontina AC, Costa AP, Dutra MF, Quincozes-Santos A, Nardin P, Bernardi CL, Wartchow KM, Lunardi PS, Gonçalves CA. Green tea (´) epigallocatechin-3-gallate reverses oxidative stress and reduces acetylcholinesterase activity in a streptozotocininduced model of dementia. Behav Brain Res. 2013; 236:186–193.

Krobitsch S and Kazantsev AG. Huntington’s disease: From molecular basis to therapeutic advances. Int J Biochem Cell Biol. 2011; 43:20-24.

Kumar P, Kalonia H, Kumar A. Huntington’s disease: Pathogenesis to animal models. Pharmacol Rep. 2010; 62:1- 14.

Zadori D, Geisz A, Vamos E, Vecsei L, Klivenyi P. Valproate ameliorates the survival and the motor performance in a transgenic mouse model of Huntington’s disease. Pharmacol Biochem Behav. 2009; 94:148-153.

Nayak A, Ansar R, Verma SK, Bonifati DM, Kishore U. Huntington's disease: An immune perspective. Neurol Res Int. 2011; 2011: 563784.

Walker FO. Huntington's disease. Lancet. 2007; 369:218- 228.

Margolis RL and Ross CA. Diagnosis of Huntington disease. Clin Chem. 2003; 49:1726-1732.

Phillips W, Shannon KW, Barker RA. The current clinical management of Huntington’s disease. Mov Disord. 2008; 23:1491-504.

Dey A and De JN. Anti-snake venom botanicals used by the ethnic groups of Purulia District, West Bengal, India. J Herbs Spices Med Plants. 2012; 18:152-165.

Dey A and De JN. Ethnomedicinal plants used by the tribals of Purulia district, West Bengal, India against gastrointestinal disorders. J Ethnopharmacol. 2012; 143:68- 80.

Man SC, Durairajan SS, Kum WF, Lu JH, Huang JD, Cheng CF, Chung V, Xu M, Li M. Systematic review on the efficacy and safety of herbal medicines for Alzheimer's disease. J Alzheimers Dis. 2008; 14:209-223.

Pedraza-Chaverrí J, Reyes-Fermín LM, Nolasco-Amaya EG, Orozco-Ibarra M, Medina-Campos ON, GonzálezCuahutencos O, Rivero-Cruz I, Mata R. ROS scavenging capacity and neuroprotective effect of alpha-mangostin against 3-nitropropionic acid in cerebellar granule neurons.

Exp Toxicol Pathol. 2009; 61:491-501.

Zhang J, Li CY, Xu MJ, Wu T, Chu JH, Liu SJ, Ju WZ. Oral bioavailability and gender-related pharmacokinetics of celastrol following administration of pure celastrol and its related tablets in rats. J Ethnopharmacol. 2012; 144:195- 200.

Sagredo O, Ramos JA, Decio A, Mechoulam R, FernándezRuiz J. Cannabidiol reduced the striatal atrophy caused 3- nitropropionic acid in vivo by mechanisms independent of the activation of cannabinoid, vanilloid TRPV1 and adenosine A2A receptors. Eur J Neurosci. 2007; 26:843-

Zhang YQ and Sarge KD. Celastrol inhibits polyglutamine aggregation and toxicity though induction of the heat shock response. J Mol Med (Berl). 2007; 85:1421-1428.

Sandhir R, Yadav A, Mehrotra A, Sunkaria A, Singh A, Sharma S. Curcumin nanoparticles attenuate neurochemical and neurobehavioral deficits in experimental model of Huntington's disease. Neuromolecular Med. 2014; 16:106- 118.

Ehrnhoefer DE, Duennwald M, Markovic P, Wacker JL, Engemann S, Roark M, Legleiter J, Marsh JL, Thompson LM, Lindquist S, Muchowski PJ, Wanker EE. Green tea (-)- epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington's

disease models. Hum Mol Genet. 2006; 15:2743-2751.

Maher P, Dargusch R, Bodai L, Gerard PE, Purcell JM, Marsh JL. ERK activation by the polyphenols fisetin and resveratrol provides neuroprotection in multiple models of Huntington's disease. Hum Mol Genet. 2011; 20:261-270.

Park JE, Lee ST, Im WS, Chu K, Kim M. Galantamine reduces striatal degeneration in 3-nitropropionic acid model of Huntington's disease. Neurosci Lett. 2008; 448:143-147.

Wu J, Jeong HK, Bulin SE, Kwon SW, Park JH, Bezprozvanny I. Ginsenosides protect striatal neurons in a cellular model of Huntington's disease. J Neurosci Res. 2009; 87:1904-1912.

Menze ET, Tadros MG, Abdel-Tawab AM, Khalifa AE. Potential neuroprotective effects of hesperidin on 3- nitropropionic acid-induced neurotoxicity in rats. Neurotoxicol. 2012; 33:1265-1275.

Lagoa R, Lopez-Sanchez C, Samhan-Arias AK, Ganan CM, Garcia-Martinez V, Gutierrez-Merino C. Kaempferol protects against rat striatal degeneration induced by 3- nitropropionic acid. J Neurochem. 2009; 111:473-487.

Binawade Y and Jagtap A. Neuroprotective Effect of lutein against 3-nitropropionic acid-induced Huntington's diseaselike symptoms: possible behavioral, biochemical, and cellular alterations. J Med Food. 2013; 16:934-943.

Kumar P, Kalonia H, Kumar A. Lycopene modulates nitric oxide pathways against 3-nitropropionic acidinduced neurotoxicity. Life Sci. 2009; 85:711-718.

Túnez I, Montilla P, Del Carmen Muñoz M, Feijóo M, Salcedo M. Protective effect of melatonin on 3- nitropropionic acid-induced oxidative stress in synaptosomes in an animal model of Huntington's disease. J Pineal Res. 2004; 37:252-256.

Kumar P and 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; 206:38-46.

Tariq M, Khan HA, Elfaki I, Al Deeb S, Al Moutaery K. Neuroprotective effect of nicotine against 3- nitropropionic acid (3-NP)-induced experimental Huntington's disease in rats. Brain Res Bull. 2005; 67:161-168.

Wu AG, Wong VK, Xu SW, Chan WK, Ng CI, Liu L, Law BY. Onjisaponin B derived from Radix Polygalae enhances autophagy and accelerates the degradation of mutant α- synuclein and huntingtin in PC-12 cells. Int J Mol Sci. 2013; 14:22618-22641.

Sandhir R and Mehrotra A. Quercetin supplementation is effective in improving mitochondrial dysfunctions induced by 3-nitropropionic acid: implications in Huntington's disease. Biochim Biophys Acta. 2013; 1832:421-430.

Pérez-De La Cruz V, González-Cortés C, Pedraza-Chaverrí J, Maldonado PD, Andrés-Martínez L, Santamaría A. Protective effect of S-allylcysteine on 3-nitropropionic acidinduced lipid peroxidation and mitochondrial dysfunction in rat brain synaptosomes. Brain Res Bull. 2006; 68:379-383.

Lam PY and Ko KM. Beneficial effect of (-)schisandrin B against 3-nitropropionic acid-induced cell death in PC12 cells. Biofact. 2012; 38:219-225.

Kumar P, Kalonia H, Kumar A. Huntington’s disease: Pathogenesis to animal models. Pharmacol Rep. 2010; 62:1- 14.

Sarkar S, Davies JE, Huang Z, Tunnacliffe A, Rubinsztein DC. Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein. J Biol Chem. 2007; 282:5641-5652.

Moya-Alvarado G, Gershoni-Emek N, Perlson E, Bronfman FC. Neurodegeneration and Alzheimer's disease (AD). What Can Proteomics Tell Us About the Alzheimer's Brain?. Mol Cell Proteomics. 2016; 15:409-425.

Berchtold NC and Cotman CW. Evolution in the Conceptualization of Dementia and Alzheimer's Disease: Greco-Roman Period to the 1960s. Neurobiol Aging. 1998; 19:173-189.

Venkatesan R, Ji E, Kim SY. Phytochemicals That Regulate Neurodegenerative Disease by Targeting Neurotrophins: A Comprehensive Review. Biomed Res Int. 2015;2015: 814068.

Davinelli S, Sapere N, Zella, D, Bracale R, Intrieri M, Scapagnini G. Pleiotropic protective effects of phytochemicals in Alzheimer’s disease. Oxid Med Cell Longev. 2012; 2012:386527.

Li M, Guo K, Ikehara S. Stem Cell Treatment for Alzheimer's Disease. Int J Mol Sci. 2014; 15:19226-19238.

De-Paula VJ, Radanovic M, Diniz BS, Forlenza OV. Alzheimer's disease. Subcell Biochem. 2012; 65:329-352.

Förstl H and Kurz A. Clinical features of Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci. 1999; 249:288- 290.

Taler V and Phillips NA. Language Performance in Alzheimer's Disease and Mild Cognitive Impairment: a comparative review. J Clin Exp Neuropsychol. 2008; 30:501–556.

Shakir T, Coulibaly AY, Kehoe PG. An exploration of potential mechanisms and translational potential of five medicinal plants for applications in Alzheimer’s disease. Am J Neurodegener Dis. 2013; 2:70-88.

Khairallah MI and Kassem LA. Alzheimer's disease: current status of etiopathogenesis and therapeutic strategies. Pak J Biol Sci. 2011; 14:257-272.

Fang L, Gou S, Fang X, Cheng L, Fleck C. Current progresses of novel natural products and their derivatives/ analogs as anti-Alzheimer candidates: an update. Mini Rev ed Chem. 2013; 13:870-887.

Kovács T. Therapy of Alzheimer disease. Neuropsychopharmacol Hung. 2009; 11:27-33.

Kim J, Lee HJ, Lee KW. Naturally occurring phytochemicals for the prevention of Alzheimer's disease. J Neurochem. 2010; 112:1415-1430.

Honjo H, Iwasa K, Fushiki S, Hosoda T, Tatsumi H, Mihara M, Hirasugi Y, Oida M, Kariya K, Kikuchi N, Kawata M. Estrogen and non-feminizing estrogen for Alzheimer's disease. Endocr J. 2003; 50:361-367.

Ghavami A, Hirst WD, Novak TJ. Selective phosphodiesterase (PDE)-4 inhibitors: a novel approach to treating memory deficit? Drugs R D. 2006; 7:63-71.

Engelborghs S, Gilles C, Ivanoiu A, Vandewoude M. Rationale and clinical data supporting nutritional intervention in Alzheimer's disease. Acta Clin Belg. 2014; 69:17-24.

Kennedy DO and Wightman EL. Herbal extracts and phytochemicals: Plant secondary metabolites and the enhancement of human brain function. Adv Nutr. 2011; 2:32-50.

Fang X, Lin X, Liang S, Zhang WD, Feng Y, Ruan KF. Phytochemical study of Hicriopteris glauca. Chem Nat Compd. 2013; 49:514-515.

Elgorashi EE, Stafford GI, Van Staden J. Acetylcholinesterase enzyme inhibitory effects of amaryllidaceae alkaloids. Planta Med. 2004; 70:260-262.

115.Heo HJ, Cho HY, Hong B, Kim HK, Kim EK, Kim BG, Shin DH. Protective effect of 4',5-dihydroxy-3',6,7- trimethoxyflavone from Artemisia asiatica against Abetainduced oxidative stress in PC12 cells. Amyloid. 2001; 3:194-201.

Park SH, Lee H, Kim HS, Kim YR, Noh SH. Optimum conditions for S- allyl-(L)-cysteine accumulation in aged garlic by RSM. Food Sci Biotechnol. 2014; 23:717-722.

Orhan I, Terzioglu S, Sener B. Alpha-onocerin: an acetylcholinesterase inhibitor from Lycopodium clavatum. Planta Med. 2003; 69:265-267.

Wang H, Xu Y, Yan J, Zhao X, Sun X, Zhang Y, Guo J, Zhu C. Acteoside protects human neuroblastoma SH-SY5Y cells against beta-amyloid-induced cell injury. Brain Res. 2009; 1283:139-147.

Zhao L, Wang JL, Liu R, Li XX, Li JF, Zhang L. Neuroprotective, anti-amyloidogenic and neurotrophic effects of apigenin in an Alzheimer's disease mouse model. Mol. 2013; 18:9949-9965.

Wei G, Chen, YB, Chen D F, Lai XP, Liu DH, Deng RD,Zhou JH, Zhang SX, Li YW, Lii H, Liu LF, Wang Q, Nie H. β-Asarone inhibits neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in an in vitro model and AβPP/PS1 mice. J Alzheimers Dis. 2013; 33:863-880.

Heo HJ, Kim DO, Shin SC, Kim MJ, Kim BG, Shin DH. Effect of antioxidant flavanone, naringenin, from Citrus junoson neuroprotection. J Agric Food Chem. 2004; 52:1520-1525.

Urbain A, Marston A, Queiroz EF, Ndjoko K, Hostettmann K. Xanthones from Gentiana campestris as new acetylcholinesterase inhibitors. Planta Med. 2004; 70:1011- 1014.

Jiang B, Du J, Liu JH, Bao YM, An LJ. Catalpol attenuates the neurotoxicity induced by beta-amyloid (1-42) in cortical neuron-glia cultures. Brain Res. 2008; 1188:139-147.

Mei Z, Yan P, Situ B, Mou Y, Liu P. Cryptotanshinione inhibits β-amyloid aggregation and protects damage from β- amyloid in SH-SY5Y cells. Neurochem Res. 2012; 37:622- 628.

Durairajan SS, Liu LF, Lu JH, Koo I, Maruyama, K, Chung SK, Huang JD, Li M. Stimulation of non-amyloidogenic processing of amyloid-β protein precursor by cryptotanshinone involves activation and translocation of ADAM10 and PKC-α. J Alzheimers Dis. 2011; 25:245-262.

Park SY and Kim DS. Discovery of natural products from Curcuma longa that protect cells from beta-amyloid insult: a drug discovery effort against Alzheimer's disease. J Nat Prod. 2002; 65:1227-1231.

Wang J, Cao F, Su E, Wu C, Zhao L, Ying R. Improving flavonoid extraction from Ginkgo biloba leaves by prefermentation processing. J Agric Food Chem. 2013; 61:5783-5791.

Ahmed T and Gilani AH. Inhibitory effect of curcuminoids on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia may explain medicinal use of turmeric in Alzheimer's disease. Pharmacol Biochem Behav. 2009; 91:554-559.

Ahmed T and Gilani AH. A comparative study of curcuminoids to measure their effect on inflammatory and apoptotic gene expression in an Aβ plus ibotenic acidinfused rat model of Alzheimer's disease. Brain Res. 2011; 1400:1-18.

Lee KY, Yoon JS, Kim ES, Kang SY, Kim YC. Antiacetylcholinesterase and anti-amnesic activities of a pregnane glycoside, cynatroside B, from Cynanchum atratum. Planta Med. 2005; 71:7-11.

Yan JJ, Kim DH, Moon YS, Jung JS, Ahn EM, Baek NI, Song DK. Protection against beta-amyloid peptideinduced memory impairment with long-term administration of extract of Angelica gigas or decursinol in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28:25-30.

Li L, Zhang X, Cui L, Wang L, Liu H, Ji H, Du Y. Ursolic acid promotes the neuroprotection by activating Nrf2 pathway after cerebral ischemia in mice. Brain Res. 2013; 1497:32-39.

Aronson S, Van Baelen B, Kavanagh S, Schwalen S. Optimal dosing of galantamine in patients with mild or moderate Alzheimer's disease: post Hoc analysis of a randomized, double-blind, placebo-controlled trial. Drugs Aging. 2009; 26:231-239.

Suh GH , Jung HY, Lee CU, Oh BH, Bae JN, Jung HY, Ju YS, Yeon BK, Park J, Hong I, Choi S, Lee JH. A prospective, double-blind, community-controlled comparison of three doses of galantamine in the treatment of mild to moderate Alzheimer's disease in a Korean population. Clin Ther. 2004; 26:1608-1618.

Zeng H, Chen Q, Zhao B. Genistein ameliorates betaamyloid peptide (25-35)-induced hippocampal neuronal apoptosis. Free Radic Biol Med. 2004; 36:180-188.

Bate C, Salmona M, Williams A. Ginkgolide B inhibits the neurotoxicity of prions or amyloid-β1-42. J Neuroinflamm. 2004;1:4.

Wang J, Li PT, Du H, Hou JC, Li WH, Pan YS, Chen HC. Tong Luo Jiu Nao injection, a traditional Chinese medicinal preparation, inhibits MIP-1β expression in brain microvascular endothelial cells injured by oxygen-glucose deprivation. J Ethnopharmacol. 2012; 141:151-157.

Xiao XQ, Zhang HY, Tang XC. Huperzine A attenuates amyloid beta-peptide fragment 25-35-induced apoptosis in rat cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation. J Neurosci Res. 2002; 67:30-36.

Zeng KW, Ko H, Yang HO, Wang XM. Icariin attenuates β-amyloid-induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells. Neuropharmacol. 2010; 59:542-550.

Xian YF, Mao QQ, Wu, JC, Su ZR, Chen JN, Lai XP, Ip SP, Lin ZX. Isorhynchophylline treatment improves the amyloid-β-induced cognitive impairment in rats via inhibition of neuronal apoptosis and tau protein hyperphosphorylation. J Alzheimers Dis. 2014; 39:331-346.

Kim TI, Lee YK, Park SG, Choi IS, Ban JO, Park HK, Nam SY, Yun YW, Han SB, Oh KW, Hong J. T l-Theanine, an amino acid in green tea, attenuates beta-amyloid-induced cognitive dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-kappaB pathways. Free Radic Biol Med. 2009; 47:1601-1610.

Zheng N, Yuan P, Li C, Wu J, Huang J. Luteolin reduces BACE1 expression through NF-κB and through estrogen receptor mediated pathways in HEK293 and SH-SY5Y cells. J Alzheimers Dis. 2015; 45:659-671.

Heo HJ, Kim DO, Shin SC, Kim MJ, Kim BG, Shin DH. Effect of antioxidant flavanone, naringenin, from Citrus junoson neuroprotection. J Agric Food Chem. 2004; 52:1520-1525.

Ma B, Meng X, Wang J, Sun J, Ren X, Qin M, Sun J, Sun G, Sun X. Notoginsenoside R1 attenuates amyloid-β- induced damage in neurons by inhibiting reactive oxygen species and modulating MAPK activation. Int Immunopharmacol. 2014; 22:151-159.

Kim SJ, Jeong HJ, Lee KM, Myung NY, An NH, Yang WM, Park SK, Lee HJ, Hong SH, Kim HM, Um JY. Epigallocatechin-3-gallate suppresses NF-kappaB activation and phosphorylation of p38 MAPK and JNK in human astrocytoma U373MG cells. J Nutr Biochem. 2007; 18:587-596.

Yoon JH, Youn K, Ho CT, Karwe MV, Jeong WS, Jun M. p-Coumaric acid and ursolic acid from Corni fructus attenuated β-amyloid(25-35)-induced toxicity through regulation of the NF-κB signaling pathway in PC12 cells. J Agric Food Chem. 2014; 62:4911-4916.

Chonpathompikunlert P, Wattanathorn J, Muchimapura S. Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer's disease. Food Chem Toxicol. 2010; 48:798- 802.

Li F, Gao B, Dong H, Shi J, Fang D. Icariin induces synoviolin expression through NFE2L1 to protect neurons from ER stress-induced apoptosis. PLoS One. 2015; 10:0119955.

Zhang L, Yu H, Zhao X, Lin X, Tan C, Cao G, Wang Z. Neuroprotective effects of salidroside against betaamyloidinduced oxidative stress in SH-SY5Y human neuroblastoma cells. Neurochem Int. 2010; 57:547-555.

Peng Q, Buz'Zard AR, Lau BH. Neuroprotective effect of garlic compounds in amyloid-beta peptideinduced apoptosis in vitro. Med Sci Monit. 2002; 8:328-337.

Chauhan NB. Effect of aged garlic extract on APP processing and tau phosphorylation in Alzheimer's transgenic model Tg2576. J Ethnopharmacol. 2006; 108:385-394.

Lu P, Mamiya T, Lu LL, Mouri A, Niwa M, Hiramatsu M, Zou LB, Nagai T, Ikejima T, Nabeshima Tl. Silibinin attenuates amyloid beta (25-35) peptide-induced memory impairments: implication of inducible nitric-oxide synthaseand tumor necrosis factor-alpha in mice. J Pharmacol Exp

Ther. 2009; 331:319-326.

Ingkaninan K, Changwijit K, Suwanborirux K. Vobasinyliboga bisindole alkaloids, potent acetylcholinesterase inhibitors from Tabernaemontana divaricata root. J Pharm Pharmacol. 2006; 58:847-852.

Urbain A, Marston A, Grilo LS, Bravo J, Purev O, Purevsuren B, Batsuren D, Reist M, Carrupt PA, Hostettmann K. Xanthones from Gentianella amarella ssp. acuta with acetylcholinesterase and monoamine oxidase inhibitory activities. 'It Good. 2008; 71:895-897.

Pan XD, Chen XC, Zhu YG, Chen LM, Zhang J, Huang TW, Ye QY, Huang HP. Tripchlorolide protects neuronal cells from microglia-mediated beta-amyloid neurotoxicity through inhibiting NF-kappaB and JNK signaling. Glia. 2009; 57:1227-1238.

Hong SY, Jeong WS, Jun M. Protective effects of the key compounds isolated from Corni fructus against β-amyloidinduced neurotoxicity in PC12 cells. Mol. 2012; 17:10831- 10845.

Chi TY, Wang LH, Ji XF, Shen L, Zou LB. Protective effect of xanthoceraside against β-amyloid-induced neurotoxicity in neuroblastoma SH-SY5Y cells. J Asian Nat Prod Res. 2013; 15:1013-1022.

Yu Y, Zhou L, Sun M, Zhou T, Zhong K, Wang H, Liu Y, Liu X, Xiao R, Ge J, Tu P, Fan DS, Lan Y, Hui C, Chui D. Xylocoside G reduces amyloid-β induced neurotoxicity by inhibiting NF-κB signaling pathway in neuronal cells. J Alzheimers Dis. 2012; 30:263-275.

Heo HJ, Cho HY, Hong B, Kim HK, Heo TR, Kim EK, Kim SK, Kim CJ, Shin DH. Ursolic acid of Origanum majorana L. reduces Abeta-induced oxidative injury. Mol Cells. 2002; 13:5-11.

O’Keane V, Frodl T, Dinan TG. A review of atypical depression in relation to the course of depression and changes in HPA axis organization.

Psychoneuroendocrinology. 2012; 37:1589-1599.

Berton O and Nestler EJ. New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci. 2006; 7:137-151.

Mitchelmore C and Gede L. Brain derived neurotrophic factor: epigenetic regulation in psychiatric disorders. Brain Res. 2014; 1586:162-172.

Evelyn B, Laura HA, Irving H, Nancy AS, Jordi A, Giovanni DG, Ron DG, Koen D, Chiyi H, Noboru I, Aimee NK, Jagdish K, Stanislav K, Jean-Pierre L, Daphna L, Herbert M, Maria EMM, Mark OB, Jose P, Maria CV, David RW, Ronald CK. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med. 2011; 9:90.

Shulman KI, Herrmann N, Walker SE. Current place of monoamine oxidase inhibitors in the treatment of depression. CNS Drugs. 2013; 27:789-797.

Gillman PK. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007; 151:737-748.

Nemeroff CB. Prevalence and management of treatment resistant depression. J Clin Psychiatry. 2007; 68:17-25.

Trivedi MH, Fava M, Wisniewski SR, Thase ME, Quitkin F, Warden D, Ritz L, Nierenberg AA, Lebowitz BD, Biggs MM, Luther JF, Shores-Wilson K, Rush AJ, STAR*D Study Team . Medication augmentation after the failure of SSRIs for depression. The New Eng J Med. 2006;

:1243-1252.

Baker CB, Johnsrud MT, Crismon ML, Rosenheck RA, Woods SW. Quantitative analysis of sponsorship bias in economic studies of antidepressants. Br J Psychiatry. 2003; 183:498-506.

Meijer WEE, Heerdink ER, Nolen WA, Herings RMC, Leufens HGM, Egberts ACG. Association of risk of abnormal bleeding with degree of serotonin reuptake inhibition by antidepressants. Arch Int Med. 2004; 164:2367-2370.

Vanderkooy JD, Kennedy SH, Aladeokin AC. Antidepressant side effects in depression patients treated in a naturalistic setting: a study of bupropion, moclobemide, paroxetine, sertraline, and venlafaxine. Can J Psychiatry. 2002; 47:174-180.

Khawam EA, Laurencic G, Malone Jr DA. Side effects of antidepressants: an overview. Cleveland Clin J Med. 2006; 73:351-361.

Papakostas GI. Tolerability of modern antidepressants. JClin Psychiatry. 2008; 69:8–13.

Linde K. St. John’s wort—an overview. Forschende Komplementarmedizin. 2009; 16:146–155.

Melo FH, Moura BA, de Sousa DP, de Vasconcelos SM, Macedo DS, Fonteles MM, Viana GS, de Sousa FC. Antidepressant-like effect of carvacrol (5-Isopropyl- 2- methylphenol) in mice: involvement of dopaminergic system. Fund Clin Pharmacol. 2011; 25:362–367.

Zotti M, Colaianna M, Morgese MG, Tucci P, Schiavone S, Avato P, Trabace L Carvacrol: from ancient flavoring to neuromodulatory agent. Mol. 2013; 18:6161–6172.

Xu Y, Ku BS, Yao HY, Ma X, Zhang YH, Li XJ. Antidepressant effect of curcumin in mice. Chin J Clin Rehab. 2005; 9:162–164.

Bhutani MK, Bishnoi M, Kulkarni SK. Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes. Pharmacol Biochem Behav. 2009; 92:39–43.

Wang R, Xu Y, Wu HL, Li YB, Li YH, Guo JB, Li XJ. The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5- HT2 receptors. Eur J Pharmacol. 2008; 578:43–50.

Xu Y, Ku B, Cui L, Li X, Barish PA, Foster TC, Ogle WO. Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res. 2007; 116:9–18.

Yabe T, Hirahara H, Harada N, Ito N, Nagai T, Sanagi T, Yamada H. Ferulic acid induces neural progenitor cell proliferation in vitro and in vivo. Neurosci. 2010; 165:515– 524.

Yin C, Gou LLY, Liu Y, Yin X, Zhang L, Jia G, Zhuang X. Antidepressant-like effects of Ltheanine in the forced swim and tail suspension tests in mice. Phytother Res. 2011; 25:1636-1639.

Xu C, Teng J, Chen W, Ge Q, Yang Z, Yu C, Yang Z, Jia W. 20(S)-protopanaxadiol, an active ginseng metabolite, exhibits strong antidepressant-like effects in animal tests. Prog. Neuropsychopharmacol Biol Psychiatry. 2010; 34:1402-1411.

Bhutada P, Mundhada Y, Bansod K, Ubgade A, Quazi M, Umathe S, Mundhada D. Reversal by quercetin of corticotrophin releasing factor induced anxiety- and depression-like effect in mice. Progr NeuroPsychopharmacol Biol Psychiatry. 2010; 34:955-960.

Yu Y, Wang R, Chen C, Du X, Ruan L, Sun J, Li J, Zhang L, O'Donnell JM, Pan J, Xu Y. Antidepressant-like effect of trans-resveratrol in chronic stress model: behavioral and neurochemical evidences. J Psychiatr Res. 2013; 47:315- 322.

Limanaqi F, Biagioni F, Mastroiacovo F, Polzella M, Lazzeri G, Fornai F. Merging the Multi-Target Effects of Phytochemicals in Neurodegeneration: From Oxidative Stress to Protein Aggregation and Inflammation. Antioxid. 2020; 9(10):1022.

Downloads

Published

2022-07-01

How to Cite

Kayode, A. A. A., Kayode, O. T., & Rotimi, D. E. (2022). Pharmacological Actions of Phytoconstituents on Neurodegenerative Disorders: doi.org/10.26538/tjnpr/v6i7.2. Tropical Journal of Natural Product Research (TJNPR), 6(7), 1019–1046. Retrieved from https://tjnpr.org/index.php/home/article/view/1341