Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Strong Binding of Phytochemicals to the Catalytic Domain of Tyrosine Hydroxylase as a Trojan Horse Decreases Dopamine in Dopaminergic Cells: Pharmaceutical Considerations in Schizophrenia and Parkinson’s Disease

Author(s): Shima Tavakol*, Elham Hoveizi, Hani Tavakol, Amin Almasi, Mansoureh Soleimani, Shadi Rabiee Motmaen, Fereshteh Azedi and Mohammad Taghi Joghataei

Volume 28, Issue 42, 2022

Published on: 24 November, 2022

Page: [3428 - 3445] Pages: 18

DOI: 10.2174/1381612829666221102151926

Price: $65

Abstract

Background: Imbalances in dopamine levels result in neurological and psychological disorders such as elevated dopamine in Parkinson’s disease.

Objective: Despite a considerable number of advertisements claiming Aloe-vera’s effectiveness in PD treatment, it has hidden long-term disadvantages for healthy people and PD patients.

Methods: In the present investigation, the impacts of Aloe-vera on dopaminergic cells were evaluated.

Results: The results indicated that the focal adhesion kinase (FAK) enhancement was in line with the Bax/Bcl2 ratio decrement, reactive oxygen specious (ROS) production, and nonsignificant alteration in the sub-G1phase of the cell cycle. It led to glial cell-derived neurotrophic factor (GDNF) upregulation but did not significantly change the BDNF level involved in depression and motor impairment recovery. These events apparently resulted in the enhancement in dopaminergic cell viability and neurite length and attenuated PI+ cells. However, it also induced neuronal nitric oxide synthase (nNOS) overexpression and nitric oxide (NO) and lactate dehydrogenase (LDH) production. Notably, docking results of the catalytic domain in tyrosine hydroxylase (TH) with the Aloe-vera constituents showed strong binding of most Aloe-vera constituents with the catalytic domain of TH, even stronger than L-tyrosine as an original substrate. Following the docking results, Aloe-vera downregulated TH protein and attenuated dopamine.

Conclusion: It can be hypothesized that Aloe-vera improves PD symptoms through enhancement in antiapoptotic markers and neurotrophic factors, while it suppresses TH and dopamine in the form of a Trojan horse, later resulting in the future deterioration of the disease symptoms. The results provide cues to pharmaceutical companies to use the active components of Aloe-vera as putative agents in neurological and psychiatric disorders and diseases to decrease dopamine in patients with enhanced dopamine levels.

« Previous Next »
[1]
Latif S, Jahangeer M, Maknoon Razia D, et al. Dopamine in Parkinson’s disease. Clin Chim Acta 2021; 522: 114-26.
[http://dx.doi.org/10.1016/j.cca.2021.08.009] [PMID: 34389279]
[2]
Wu J, Xiao H, Sun H, Zou L, Zhu LQ. Role of dopamine receptors in ADHD: A systematic meta-analysis. Mol Neurobiol 2012; 45(3): 605-20.
[http://dx.doi.org/10.1007/s12035-012-8278-5] [PMID: 22610946]
[3]
Swanson JM, Flodman P, Kennedy J, et al. Dopamine genes and ADHD. Neurosci Biobehav Rev 2000; 24(1): 21-5.
[http://dx.doi.org/10.1016/S0149-7634(99)00062-7] [PMID: 10654656]
[4]
Wise RA, Robble MA. Dopamine and addiction. Annu Rev Psychol 2020; 71(1): 79-106.
[http://dx.doi.org/10.1146/annurev-psych-010418-103337] [PMID: 31905114]
[5]
Maia TV, Frank MJ. An integrative perspective on the role of dopamine in schizophrenia. Biol Psychiatry 2017; 81(1): 52-66.
[http://dx.doi.org/10.1016/j.biopsych.2016.05.021] [PMID: 27452791]
[6]
Guerin B, Hoorens S, Khodyakov D, Yaqub O. A growing and ageing population–global societal trends to 2030: thematic report 1 Re-port. Santa Monica, CA: RAND Corporation 2015.
[7]
Tavakol S, Musavi SMM, Tavakol B, Hoveizi E, Ai J, Rezayat SM. Noggin along with a self-assembling peptide nanofiber containing long motif of laminin induces tyrosine hydroxylase gene expression. Mol Neurobiol 2017; 54(6): 4609-16.
[http://dx.doi.org/10.1007/s12035-016-0006-0] [PMID: 27389777]
[8]
Goldberg JA, Guzman JN, Estep CM, et al. Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson’s disease. Nat Neurosci 2012; 15(10): 1414-21.
[http://dx.doi.org/10.1038/nn.3209] [PMID: 22941107]
[9]
Wong E, Cuervo AM. Autophagy gone awry in neurodegenerative diseases. Nat Neurosci 2010; 13(7): 805-11.
[http://dx.doi.org/10.1038/nn.2575] [PMID: 20581817]
[10]
Moors TE, Hoozemans JJM, Ingrassia A, et al. Therapeutic potential of autophagy-enhancing agents in Parkinson’s disease. Mol Neurodegener 2017; 12(1): 11.
[http://dx.doi.org/10.1186/s13024-017-0154-3] [PMID: 28122627]
[11]
Mohammadinejad R, Moosavi MA, Tavakol S, et al. Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles. Autophagy 2019; 15(1): 4-33.
[http://dx.doi.org/10.1080/15548627.2018.1509171] [PMID: 30160607]
[12]
Tavakol S, Hoveizi E, Tavakol B, et al. Small molecule of sphingosine as a rescue of dopaminergic cells: A cell therapy approach in neurodegenerative diseases therapeutics. J Cell Physiol 2019; 234(7): 11401-10.
[http://dx.doi.org/10.1002/jcp.27774] [PMID: 30623407]
[13]
Bagheri M, Roghani M, Joghataei MT, Mohseni S. Genistein inhibits aggregation of exogenous amyloid-beta1–40 and alleviates astro-gliosis in the hippocampus of rats. Brain Res 2012; 1429: 145-54.
[http://dx.doi.org/10.1016/j.brainres.2011.10.020] [PMID: 22079317]
[14]
Abdolmaleky HM, Pajouhanfar S, Faghankhani M, Joghataei MT, Mostafavi A, Thiagalingam S. Antipsychotic drugs attenuate aberrant DNA methylation of DTNBP1 (dysbindin) promoter in saliva and post-mortem brain of patients with schizophrenia and psychotic bipo-lar disorder. Am J Med Genet B Neuropsychiatr Genet 2015; 168(8): 687-96.
[http://dx.doi.org/10.1002/ajmg.b.32361] [PMID: 26285059]
[15]
Kesby JP, Eyles DW, McGrath JJ, Scott JG. Dopamine, psychosis and schizophrenia: The widening gap between basic and clinical neu-roscience. Transl Psychiatry 2018; 8(1): 30.
[http://dx.doi.org/10.1038/s41398-017-0071-9] [PMID: 29382821]
[16]
Brisch R, Saniotis A, Wolf R, et al. The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: Old fashioned, but still in vogue. Front Psychiatry 2014; 5: 47.
[PMID: 24904434]
[17]
Tavakol S, Saber R, Hoveizi E, et al. Self-assembling peptide nanofiber containing long motif of laminin induces neural differentiation, tubulin polymerization, and neurogenesis: In vitro, ex vivo, and in vivo studies. Mol Neurobiol 2016; 53(8): 5288-99.
[http://dx.doi.org/10.1007/s12035-015-9448-z] [PMID: 26427854]
[18]
Tavakol S, Saber R, Hoveizi E, Aligholi H, Ai J, Rezayat SM. Chimeric self-assembling nanofiber containing bone marrow homing pep-tide’s motif induces motor neuron recovery in animal model of chronic spinal cord injury; an in vitro and in vivo investigation. Mol Neurobiol 2016; 53(5): 3298-308.
[http://dx.doi.org/10.1007/s12035-015-9266-3] [PMID: 26063594]
[19]
Tavakol S, Mousavi SMM, Tavakol B, Hoveizi E, Ai J, Sorkhabadi SMR. Mechano-transduction signals derived from self-assembling peptide nanofibers containing long motif of laminin influence neurogenesis in in vitro and in vivo. Mol Neurobiol 2017; 54(4): 2483-96.
[http://dx.doi.org/10.1007/s12035-016-9836-z] [PMID: 26984600]
[20]
Tavakol S, Aligholi H, Gorji A, et al. Thermogel nanofiber induces human endometrial-derived stromal cells to neural differentiation: In vitro and in vivo studies in rat. J Biomed Mater Res A 2014; 102(12): 4590-7.
[PMID: 24532561]
[21]
Ahmadirad N, Fathollahi Y, Janahmadi M, et al. Low-frequency electrical stimulation reduces the impairment in synaptic plasticity fol-lowing epileptiform activity in rat hippocampal slices through α1, But Not α2, adrenergic receptors. Neuroscience 2019; 406: 176-85.
[http://dx.doi.org/10.1016/j.neuroscience.2019.03.007] [PMID: 30872164]
[22]
Hoveizi E, Ebrahimi-Barough S, Tavakol S, Sanamiri K. In vitro differentiation of human iPS cells into neural like cells on a biomimetic polyurea. Mol Neurobiol 2017; 54(1): 601-7.
[http://dx.doi.org/10.1007/s12035-015-9663-7] [PMID: 26746669]
[23]
Yari A, Sarveazad A, Asadi E, et al. Efficacy of Crocus sativus L. on reduction of cadmium-induced toxicity on spermatogenesis in adult rats. Andrologia 2016; 48(10): 1244-52.
[http://dx.doi.org/10.1111/and.12568] [PMID: 27135275]
[24]
Ghasemi Hamidabadi H, Rezvani Z, Nazm Bojnordi M, et al. Chitosan-intercalated montmorillonite/poly (vinyl alcohol) nanofibers as a platform to guide neuronlike differentiation of human dental pulp stem cells. ACS Appl Mater Interfaces 2017; 9(13): 11392-404.
[http://dx.doi.org/10.1021/acsami.6b14283] [PMID: 28117963]
[25]
Barnes PM, Bloom B, Nahin RL, Stussman BJ. Costs of complementary and alternative medicine (CAM) and frequency of visits to CAM practitioners, United States, 2007 2009.
[26]
Hamman J. Composition and applications of Aloe vera leaf gel. Molecules 2008; 13(8): 1599-616.
[http://dx.doi.org/10.3390/molecules13081599] [PMID: 18794775]
[27]
Rahmani A, Aldebasi Y, Srikar S, Khan A, Aly S. Aloe vera: Potential candidate in health management via modulation of biological ac-tivities. Pharmacogn Rev 2015; 9(18): 120-6.
[http://dx.doi.org/10.4103/0973-7847.162118] [PMID: 26392709]
[28]
Fé JLM, Coelho CA, Damascena GM, et al. Aloe vera as vehicle to mineral trioxide aggregate: study in bone repair. Rev Odontol UNESP 2014; 43(5): 299-304.
[http://dx.doi.org/10.1590/rou.2014.048]
[29]
Rasoulian B, Almasi A, Hoveizi E, et al. Strong binding active constituents of phytochemical to BMPR1A promote bone regeneration: In vitro, in silico docking, and in vivo studies. J Cell Physiol 2019; 234(8): 14246-58.
[http://dx.doi.org/10.1002/jcp.28121] [PMID: 30656682]
[30]
Jones K, Hughes J, Hong M, Jia Q, Orndorff S. Modulation of melanogenesis by aloesin: A competitive inhibitor of tyrosinase. Pigment Cell Res 2002; 15(5): 335-40.
[http://dx.doi.org/10.1034/j.1600-0749.2002.02014.x] [PMID: 12213089]
[31]
Bisaglia M, Greggio E, Maric D, Miller DW, Cookson MR, Bubacco L. α-Synuclein overexpression increases dopamine toxicity in BE(2)-M17 cells. BMC Neurosci 2010; 11(1): 41.
[http://dx.doi.org/10.1186/1471-2202-11-41] [PMID: 20334701]
[32]
Kupcsik L. Estimation of cell number based on metabolic activity: The MTT reduction assay. Mammalian Cell Viability: Methods and Protocols 2011; 13-9.
[http://dx.doi.org/10.1007/978-1-61779-108-6_3]
[33]
Chan FKM, Moriwaki K, Rosa MJ. Detection of necrosis by release of lactate dehydrogenase activity. Immune Homeostasis: Methods and Protocols 2013; 65-70.
[http://dx.doi.org/10.1007/978-1-62703-290-2_7]
[34]
Singh SP, Deb CR, Ahmed SU, Saratchandra Y, Konwar BK. Molecular docking simulation analysis of the interaction of dietary flavo-nols with heat shock protein 90. J Biomed Res 2015; 30: 67.
[PMID: 26423731]
[35]
Parveen Z, Sulaman Nawaz M, Shakil S. Molecular docking study of catecholamines and [4-(propan-2-yl) phenyl] carbamic acid with tyrosine hydroxylase. CNS Neurol Disord Drug Targets 2012; 11: 463-8.
[36]
Sultana N, Najam R. Alterations in neurobehavioral and brain neurotransmitters by Aloe vera (L.) Burm. F and vitamin E. Int J Res Ayurveda Pharm 2012; 3: 795-800.
[37]
Martin SS, Vuori K. Regulation of Bcl-2 proteins during anoikis and amorphosis. Biochim Biophys Acta 2004; 1692: 145-57.
[38]
Kurenova E, Xu LH, Yang X, et al. Focal adhesion kinase suppresses apoptosis by binding to the death domain of receptor-interacting protein. Mol Cell Biol 2004; 24(10): 4361-71.
[http://dx.doi.org/10.1128/MCB.24.10.4361-4371.2004] [PMID: 15121855]
[39]
Abbaoui A, Hiba OE, Gamrani H. Neuroprotective potential of Aloe arborescens against copper induced neurobehavioral features of Parkinson’s disease in rat. Acta Histochem 2017; 119(5): 592-601.
[http://dx.doi.org/10.1016/j.acthis.2017.06.003] [PMID: 28619286]
[40]
Rakha P, Parle M. Aloe vera juice: An anti-parkinsonian agent. Int J Nat Product Sci 2012.
[41]
Langmead L, Makins RJ, Rampton DS. Anti-inflammatory effects of Aloe vera gel in human colorectal mucosa in vitro. Aliment Pharmacol Ther 2004; 19(5): 521-7.
[http://dx.doi.org/10.1111/j.1365-2036.2004.01874.x] [PMID: 14987320]
[42]
Zhao Y, Haney MJ, Gupta R, et al. GDNF-transfected macrophages produce potent neuroprotective effects in Parkinson’s disease mouse model. PLoS One 2014; 9(9): e106867.
[http://dx.doi.org/10.1371/journal.pone.0106867] [PMID: 25229627]
[43]
Sullivan AM, O’Keeffe GW. Neurotrophic factor therapy for Parkinson’s disease: Past, present and future. Neural Regen Res 2016; 11(2): 205-7.
[http://dx.doi.org/10.4103/1673-5374.177710] [PMID: 27073356]
[44]
Wang Y, Liu H, Zhang BS, Soares JC, Zhang XY. Low BDNF is associated with cognitive impairments in patients with Parkinson’s dis-ease. Parkinsonism Relat Disord 2016; 29: 66-71.
[http://dx.doi.org/10.1016/j.parkreldis.2016.05.023] [PMID: 27245919]
[45]
Scalzo P, Kümmer A, Bretas TL, Cardoso F, Teixeira AL. Serum levels of brain-derived neurotrophic factor correlate with motor im-pairment in Parkinson’s disease. J Neurol 2010; 257(4): 540-5.
[http://dx.doi.org/10.1007/s00415-009-5357-2] [PMID: 19847468]
[46]
Martinowich K, Manji H, Lu B. New insights into BDNF function in depression and anxiety. Nat Neurosci 2007; 10(9): 1089-93.
[http://dx.doi.org/10.1038/nn1971] [PMID: 17726474]
[47]
Wang Y, Liu H, Du XD, et al. Association of low serum BDNF with depression in patients with Parkinson’s disease. Parkinsonism Relat Disord 2017; 41: 73-8.
[http://dx.doi.org/10.1016/j.parkreldis.2017.05.012] [PMID: 28576603]
[48]
Bagewadi HG, Khan AA. Investigation of antiparkinsonian effect of Aloe vera on haloperidol induced experimental animal model. Indian J Pharm Biol Res 2015; 3: 108.
[http://dx.doi.org/10.30750/ijpbr.3.1.15]
[49]
Tritsch NX, Ding JB, Sabatini BL. Dopaminergic neurons inhibit striatal output through non-canonical release of GABA. Nature 2012; 490(7419): 262-6.
[http://dx.doi.org/10.1038/nature11466] [PMID: 23034651]
[50]
Tritsch NX, Granger AJ, Sabatini BL. Mechanisms and functions of GABA co-release. Nat Rev Neurosci 2016; 17(3): 139-45.
[http://dx.doi.org/10.1038/nrn.2015.21] [PMID: 26865019]
[51]
LeWitt PA, Rezai AR, Leehey MA, et al. AAV2-GAD gene therapy for advanced Parkinson’s disease: A double-blind, sham-surgery controlled, randomised trial. Lancet Neurol 2011; 10(4): 309-19.
[http://dx.doi.org/10.1016/S1474-4422(11)70039-4] [PMID: 21419704]
[52]
Bagewadi HG, Rathor N. Effect of Aloe vera on animal models of Parkinson disease in mice. Int J Pharm Bio Sci 2014; 5: 549-59.
[53]
Błaszczyk JW. Parkinson’s disease and neurodegeneration: GABA-collapse hypothesis. Front Neurosci 2016; 10: 269.
[http://dx.doi.org/10.3389/fnins.2016.00269] [PMID: 27375426]
[54]
Samdani AF, Newcamp C, Resink A, et al. Differential susceptibility to neurotoxicity mediated by neurotrophins and neuronal nitric oxide synthase. J Neurosci 1997; 17(12): 4633-41.
[http://dx.doi.org/10.1523/JNEUROSCI.17-12-04633.1997] [PMID: 9169524]
[55]
Du J, Hull EM. Effects of testosterone on neuronal nitric oxide synthase and tyrosine hydroxylase. Brain Res 1999; 836(1-2): 90-8.
[http://dx.doi.org/10.1016/S0006-8993(99)01618-2] [PMID: 10415408]
[56]
Sanchez-Padilla J, Guzman JN, Ilijic E, et al. Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase. Nat Neurosci 2014; 17(6): 832-40.
[http://dx.doi.org/10.1038/nn.3717] [PMID: 24816140]
[57]
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Some drugs and herbal products. IARC Monogr Eval Carcinog Risks Hum 2016; 108: 7-419.
[PMID: 29905444]
[58]
Avila H, Rivero J, Herrera F, Fraile G. Cytotoxicity of a low molecular weight fraction from Aloe vera (Aloe barbadensis Miller) gel. Toxicon 1997; 35(9): 1423-30.
[http://dx.doi.org/10.1016/S0041-0101(97)00020-2] [PMID: 9403965]
[59]
du Plessis LH, Hamman JH. In vitro evaluation of the cytotoxic and apoptogenic properties of Aloe whole leaf and gel materials. Drug Chem Toxicol 2014; 37(2): 169-77.
[http://dx.doi.org/10.3109/01480545.2013.834356] [PMID: 24111784]
[60]
Asgharzade S, Rafieian-Kopaei M, Mirzaeian A, Reiisi S, Salimzadeh L. Aloe vera toxic effects: Expression of inducible nitric oxide synthase (iNOS) in testis of Wistar rat. Iran J Basic Med Sci 2015; 18(10): 967-73.
[PMID: 26730330]
[61]
Pandiri AR, Sills RC, Hoenerhoff MJ, et al. Aloe vera non-decolorized whole leaf extract-induced large intestinal tumors in F344 rats share similar molecular pathways with human sporadic colorectal tumors. Toxicol Pathol 2011; 39(7): 1065-74.
[http://dx.doi.org/10.1177/0192623311422081] [PMID: 21937742]
[62]
Williams LD, Burdock GA, Shin E, et al. Safety studies conducted on a proprietary high-purity Aloe vera inner leaf fillet preparation, Qmatrix®. Regul Toxicol Pharmacol 2010; 57(1): 90-8.
[http://dx.doi.org/10.1016/j.yrtph.2010.01.002] [PMID: 20096744]
[63]
Sehgal I, Winters WD, Scott M, Kousoulas K. An in vitro and in vivo toxicologic evaluation of a stabilized Aloe vera gel supplement drink in mice. Food Chem Toxicol 2013; 55: 363-70.
[http://dx.doi.org/10.1016/j.fct.2013.01.012] [PMID: 23376510]
[64]
Paes-Leme AA, Motta ES, De Mattos JCP, Dantas FJS, Bezerra RJAC, Caldeira-de-Araujo A. Assessment of Aloe vera (L.) genotoxic potential on Escherichia coli and plasmid DNA. J Ethnopharmacol 2005; 102(2): 197-201.
[http://dx.doi.org/10.1016/j.jep.2005.06.013] [PMID: 16054315]
[65]
Guo X, Mei N. Aloe vera: A review of toxicity and adverse clinical effects. J Environ Sci Health Part C Environ Carcinog Ecotoxicol Rev 2016; 34(2): 77-96.
[http://dx.doi.org/10.1080/10590501.2016.1166826] [PMID: 26986231]
[66]
Yokohira M, Matsuda Y, Suzuki S, et al. Equivocal colonic carcinogenicity of Aloe arborescens Miller var. natalensis berger at high-dose level in a Wistar Hannover rat 2-y study. J Food Sci 2009; 74(2): T24-30.
[http://dx.doi.org/10.1111/j.1750-3841.2009.01070.x] [PMID: 19323775]
[67]
National Toxicology Program. Photocarcinogenesis study of Aloe vera [CAS NO. 481-72-1(Aloe-emodin)] in SKH-1 mice (simulated solar light and topical application study). Natl Toxicol Program Tech Rep Ser 2010; (553): 7-33.
[PMID: 21031007]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy