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2000
Volume 22, Issue 1
  • ISSN: 1875-6921
  • E-ISSN: 1875-6913

Abstract

Introduction

Parkinson’s disease is increasingly prevalent among the elderly. This study aimed to explore the potential of Zinda Tilismath, a traditional Unani medicine, in mitigating Parkinson's disease symptoms.

Methods

Male Sprague-Dawley rats were used to evaluate the effectiveness of Zinda Tilismath in paraquat-induced Parkinsonism. The rats were divided into six groups: a negative control group, a positive control group, a group treated with the standard drug Selegiline, and three groups receiving different doses of Zinda Tilismath (high, medium, and low). To assess motor function and locomotion, the rats were subjected to behavioral tests, including the Rotarod, Actophotometer, and bar tests. Additionally, biochemical analyses measured dopamine levels and acetylcholinesterase (AChE) activity, while histopathological examinations were performed to substantiate neuroprotective effects. The study also included docking analyses to explore the interactions between the active components of Zinda Tilismath and the proteins MAO-B and PINK1 which are implicated in Parkinson's disease.

Results and Discussion

Docking studies revealed significant binding affinities of Zinda Tilismath components such as camphor (Binding energy kcal/mol -6.9, -5.9), L-limonene (-6.8, -5.9), Tetradecane (-5.9, -4.4) Decane (-5.2, -3.8), Isoborneol (-6.4, -6.3), Alpha pinene (-6.6, -6.2) with MAO-B and PINK1 genes, indicating potential therapeutic effects. Acute toxicity studies showed no adverse effects at 2000 mg/kg, establishing the safety of Zinda Tilismath. studies demonstrated that Zinda Tilismath at mid-dose improved motor function and locomotion in the Rotarod (105.0 ± 3.60s), Actophotometer (261 ± 21.33) and Bar test (15.67 ± 0.88) where lower dose also displayed an improved motor and locomotion in the Rotarod (98.00 ± 2.30), Actophotometer (231 ± 19.06) and Bar test (12.33 ± 1.20) in comparison to Positive control [Rotarod (28.00 ± 49.2), Actophotometer (88.67 ± 17.42), Bartest (2.33 ± 0.33)]. The results of the test drug are comparable to the standard drug Selegiline. Biochemical assays confirmed increased dopamine levels with Zinda Tilismath as compared to disease-induced group and reduced AChE activity as compared to positive control. Histopathological analysis indicated neuroprotective effects in the substantia nigra region of the brain.

Conclusion

Zinda Tilismath exhibits promising neuroprotective effects in a paraquat-induced Parkinsonism model, comparable to Selegiline. These findings suggest its potential as a safe and effective alternative treatment for Parkinson's disease, warranting further investigation. Zinda Tilismath exhibits possible neuroprotective advantages, however, certain limitations must be acknowledged. This encompasses dependence on docking studies lacking experimental validation, insufficient exploration of long-term toxicity, and unclear modes of action. Furthermore, obstacles in applying findings to clinical settings, like interspecies variations and pharmacokinetics, must be addressed. Comprehensive research is vital to determine its effectiveness, safety, and therapeutic potential.

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References

  1. BidesiN.S.R. AndersenV.I. WindhorstA.D. ShalgunovV. HerthM.M. The role of neuroimaging in Parkinson’s disease.J. Neurochem.2021159466068910.1111/jnc.15516 34532856
    [Google Scholar]
  2. DorseyE.R. ElbazA. NicholsE. Global, regional, and national burden of Parkinson’s disease, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016.Lancet Neurol.2018171193995310.1016/S1474‑4422(18)30295‑3 30287051
    [Google Scholar]
  3. DauerW. PrzedborskiS. Parkinson’s disease.Neuron200339688990910.1016/S0896‑6273(03)00568‑3 12971891
    [Google Scholar]
  4. PoorkajP. NuttJ.G. JamesD. Parkin mutation analysis in clinic patients with early‐onset Parkinson’s disease.Am. J. Med. Genet. A.2004129A1445010.1002/ajmg.a.30157 15266615
    [Google Scholar]
  5. LeroyE. BoyerR. AuburgerG. The ubiquitin pathway in Parkinson’s disease.Nature1998395670145145210.1038/26652 9774100
    [Google Scholar]
  6. SandersL.H. LaganièreJ. CooperO. LRRK2 mutations cause mitochondrial DNA damage in iPSC-derived neural cells from Parkinson’s disease patients: Reversal by gene correction.Neurobiol. Dis.20146238138610.1016/j.nbd.2013.10.013 24148854
    [Google Scholar]
  7. BonifatiV. RizzuP. BarenV.M.J. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.Science2003299560425625910.1126/science.1077209 12446870
    [Google Scholar]
  8. ValenteE.M. Abou-SleimanP.M. CaputoV. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1.Science200430456741158116010.1126/science.1096284 15087508
    [Google Scholar]
  9. SchragA. ModiS. HothamS. MerrittR. KhanK. GrahamL. Patient experiences of receiving a diagnosis of Parkinson’s disease.J. Neurol.201826551151115710.1007/s00415‑018‑8817‑8 29546451
    [Google Scholar]
  10. BieD.R.M.A. ClarkeC.E. EspayA.J. FoxS.H. LangA.E. Initiation of pharmacological therapy in Parkinson’s disease: When, why, and how.Lancet Neurol.202019545246110.1016/S1474‑4422(20)30036‑3 32171387
    [Google Scholar]
  11. SakoW. KogoY. KoebisM. Comparative efficacy and safety of adjunctive drugs to levodopa for fluctuating Parkinson’s disease - network meta-analysis.NPJ Parkinsons Dis.20239114310.1038/s41531‑023‑00589‑8 37853009
    [Google Scholar]
  12. SivanandyP. LeeyT.C. XiangT.C. Systematic review on parkinson’s disease medications, emphasizing on three recently approved drugs to control parkinson’s symptoms.Int. J. Environ. Res. Public Health202119136410.3390/ijerph19010364 35010624
    [Google Scholar]
  13. LucaD.D.G. ReyesN.G.D. FoxS.H. Newly approved and investigational drugs for motor symptom control in Parkinson’s disease.Drugs202282101027105310.1007/s40265‑022‑01747‑7 35841520
    [Google Scholar]
  14. BaroeP. SantangeloG. MorganteL. OnofrjM. MecoG. A randomized clinical trial to evaluate the effects of rasagiline on depressive symptoms in non-demented Parkinson’s disease patients.Eur. J. Neurol.20152281184119110.1111/ene.12724
    [Google Scholar]
  15. Guidelines for diagnosis and management of childhood epilepsy.Indian Pediatr.2009468681698 19717860
    [Google Scholar]
  16. MahaleB.M. MahaleD.S. ShaikhA.Z. Natural Herbs used in normal Cough and Cold Condition.Res J Phar Phytochem20221429810210.52711/0975‑4385.2022.00018
    [Google Scholar]
  17. KumarK.A. ChoudharyR.K. AnandY. VidyaB. SolomonR. Determination of chemical composition of essential oil portion of reputed marketed unani formulation Zinda Tilismath.Int. J. Pharm. Pharm. Sci.201136768
    [Google Scholar]
  18. McConkeyB.J. SobolevV. EdelmanM. The performance of current methods in ligand-protein docking.Curr. Sci.200283845855
    [Google Scholar]
  19. MuhammadS. FatimaN. In silico analysis and molecular docking studies of potential angiotensin-converting enzyme inhibitor using quercetin glycosides.Pharmacogn. Mag.2015114212310.4103/0973‑1296.157712 26109757
    [Google Scholar]
  20. HaghighiO. DavaeifarS. ZahiriH.S. MalekiH. NoghabiK.A. Homology modeling and molecular docking studies of glutamate dehydrogenase (GDH) from Cyanobacterium synechocystis sp. PCC 6803.Int. J. Pept. Res. Ther.202026278379310.1007/s10989‑019‑09886‑4
    [Google Scholar]
  21. HosseiniM. ChenW. XiaoD. WangC. Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs.Precis. Clin. Med.20214111610.1093/pcmedi/pbab001 33842834
    [Google Scholar]
  22. AliA. MirG.J. AyazA. In silico analysis and molecular docking studies of natural compounds of Withania somnifera against bovine NLRP9.J. Mol. Model.202329617110.1007/s00894‑023‑05570‑z 37155030
    [Google Scholar]
  23. CzerniczyniecA. BustamanteJ. Lores-ArnaizS. Modulation of brain mitochondrial function by deprenyl.Neurochem. Int.200648323524110.1016/j.neuint.2005.09.006 16289465
    [Google Scholar]
  24. FischerE. Influence of configuration on enzyme activity.Ber. Dtsch. Chem. Ges.18942732985299310.1002/cber.18940270364
    [Google Scholar]
  25. RollR. Höfer-BosseTh. And Kayser D. New perspectives in acute toxicity testing of chemicals.Toxicol. Lett.1986Suppl. 3186
    [Google Scholar]
  26. DienerW. SchledeE. Acute toxic class methods: Alternatives to LD/LC50 tests.Altern. Anim. Exp.1999163129134 11107319
    [Google Scholar]
  27. LipnickR.L. CotruvoJ.A. HillR.N. Comparison of the up-and-down, conventional LD50, and fixed-dose acute toxicity procedures.Food Chem. Toxicol.199533322323110.1016/0278‑6915(94)00136‑C 7896233
    [Google Scholar]
  28. ChanP.K. HayesA.W. Chapter 16 Acute Toxicity and Eye Irritancy Principles and Methods of Toxicology.3rd edNew York, USARaven Press, Ltd.1994
    [Google Scholar]
  29. OECD OECD Guidance document on the recognition, assessment and use of clinical signs as human endpoints for experimental animals used in safety evaluation.2002Available from:https://www.oecd.org/en/publications/guidance-document-on-the-recognition-assessment-and-use-of-clinical-signs-as-human-endpoints-for-experimental-animals-used-in-safety-evaluation_9789264078376-en.html [cited 2023 28 March]
  30. BidhanM. MukeshB.C. KumarT.A. General guidelines for safety/toxicity evaluation of ayurvedic formulations.J Drug Res Ayurvadic Sci2023819193
    [Google Scholar]
  31. HauserR.A. SilverD. ChoudhryA. EyalE. Randomized, controlled trial of rasagiline as an add-on to dopamine agonists in Parkinson’s disease.Mov. Disord.20142981028103410.1002/mds.25877
    [Google Scholar]
  32. ChrempfW. FauserM. WieneckeM. BrownS. Rasagiline improves polysomnographic sleep parameters in patients with Parkinson’s disease: A double-blind, baseline-controlled trial.In: Eur. J. Neurol.201825467267910.1111/ene.13567
    [Google Scholar]
  33. WebsterR. Dopamine (DA).In: Neurotransmitters, drugs and brain function.Hoboken, New JerseyJohn Wiley & Sons200113716110.1002/0470846577.ch7
    [Google Scholar]
  34. ChangY. WangL.B. LiD. LeiK. LiuS.Y. Efficacy of rasagiline for the treatment of Parkinson’s disease: An updated meta-analysis.Ann. Med.201749542143410.1080/07853890.2017.1293285 28293967
    [Google Scholar]
  35. WuY. KazumuraK. MaruyamaW. OsawaT. NaoiM. Rasagiline and selegiline suppress calcium efflux from mitochondria by PK11195-induced opening of mitochondrial permeability transition pore: A novel anti-apoptotic function for neuroprotection.J. Neural Transm.2015122101399140710.1007/s00702‑015‑1398‑0 25863936
    [Google Scholar]
  36. BindaC. HubálekF. LiM. Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class.J. Med. Chem.20044771767177410.1021/jm031087c 15027868
    [Google Scholar]
  37. MarcosF. SofiaN. KarlaS. NaF-C. EmiliaB. An effective novel delivery strategy of rasagiline for parkinson’s disease.Int. J. Pharm.20114191-227128010.1016/j.ijpharm.2011.07.029
    [Google Scholar]
  38. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: The PRESTO study.Arch. Neurol.200562224124810.1001/archneur.62.2.241 15710852
    [Google Scholar]
  39. TianZ. WangX. HanT. SunC. Selegiline ameliorated dyslipidemia and hepatic steatosis in high-fat diet mice.Int. Immunopharmacol.202311710990110.1016/j.intimp.2023.109901 36822098
    [Google Scholar]
  40. ChenS. ChanP. SunS. The recommendations of Chinese Parkinson’s disease and movement disorder society consensus on therapeutic management of Parkinson’s disease.Transl. Neurodegener.2016511210.1186/s40035‑016‑0059‑z 27366321
    [Google Scholar]
  41. TambascoN. RomoliM. CalabresiP. Levodopa in Parkinson’s disease: Current status and future developments.Curr. Neuropharmacol.20181681239125210.2174/1570159X15666170510143821 28494719
    [Google Scholar]
  42. GershanikO.S. Improving l ‐dopa therapy: The development of enzyme inhibitors.Mov. Disord.201530110311310.1002/mds.26050 25335824
    [Google Scholar]
  43. KakishJ. TavassolyO. LeeJ.S. Rasagiline, a suicide inhibitor of monoamine oxidases, binds reversibly to α-synuclein.ACS Chem. Neurosci.20156234735510.1021/cn5002914 25514361
    [Google Scholar]
  44. GandhiS. MuqitM.M. StanyerL. PINK1 protein in normal human brain and Parkinson’s disease.Brain200612971720173110.1093/brain/awl114 16702191
    [Google Scholar]
  45. GeggM.E. CooperJ.M. SchapiraA.H.V. TaanmanJ.W. Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in dopaminergic cells.PLoS One200943e475610.1371/journal.pone.0004756 19270741
    [Google Scholar]
  46. HayashidaA. LiY. YoshinoH. The identified clinical features of Parkinson’s disease in homo-, heterozygous and digenic variants of PINK1.Neurobiol. Aging202197146.e1146.e1310.1016/j.neurobiolaging.2020.06.017 32713623
    [Google Scholar]
  47. SchneiderS.A. KleinC. PINK1 type of young-onset parkinson disease.In: Adam MP, Ardinger HH, Pagon RA, et al., Eds., GeneReviews(R). Seattle, WA, USA: University of Washington1993
    [Google Scholar]
  48. BonifatiV. RohéC.F. BreedveldG.J. Early-onset parkinsonism associated with PINK1 mutations.Neurology2005651879510.1212/01.wnl.0000167546.39375.82 16009891
    [Google Scholar]
  49. EggersC. SchmidtA. HagenahJ. Progression of subtle motor signs in PINK1 mutation carriers with mild dopaminergic deficit.Neurology201074221798180510.1212/WNL.0b013e3181e0f79c 20513816
    [Google Scholar]
  50. KastenM. HartmannC. HampfJ. Genotype‐phenotype relations for the Parkinson’s disease genes Parkin, PINK1, DJ1: MDSGene systematic review.Mov. Disord.201833573074110.1002/mds.27352 29644727
    [Google Scholar]
  51. HouY. DanX. BabbarM. Ageing as a risk factor for neurodegenerative disease.Nat. Rev. Neurol.2019151056558110.1038/s41582‑019‑0244‑7 31501588
    [Google Scholar]
  52. PickrellA.M. YouleR.J. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease.Neuron201585225727310.1016/j.neuron.2014.12.007 25611507
    [Google Scholar]
  53. PrzedborskiS. VilaM. Jackson-LewisV. Series introduction: Neurodegeneration: What is it and where are we?J. Clin. Invest.2003111131010.1172/JCI200317522 12511579
    [Google Scholar]
  54. ArenaG. ValenteE.M. PINK1 in the limelight: Multiple functions of an eclectic protein in human health and disease.J. Pathol.2017241225126310.1002/path.4815 27701735
    [Google Scholar]
  55. BoonW.R. The chemistry and mode of action of the bipyridylium herbicides diquat and paraquat.Outlook Agric.19644416317010.1177/003072706400400403
    [Google Scholar]
  56. SmithL.L. Mechanism of paraquat toxicity in lung and its relevance to treatment.Hum. Toxicol.198761313610.1177/096032718700600105 3546084
    [Google Scholar]
  57. FrancoR. LiS. Rodriguez-RochaH. BurnsM. PanayiotidisM.I. Molecular mechanisms of pesticide-induced neurotoxicity: Relevance to Parkinson’s disease.Chem. Biol. Interact.2010188228930010.1016/j.cbi.2010.06.003 20542017
    [Google Scholar]
  58. Dinis-OliveiraR.J. DuarteJ.A. Sánchez-NavarroA. RemiãoF. BastosM.L. CarvalhoF. Paraquat poisonings: Mechanisms of lung toxicity, clinical features, and treatment.Crit. Rev. Toxicol.2008381137110.1080/10408440701669959 18161502
    [Google Scholar]
  59. WunnapukK. MohammedF. GawarammanaI. Prediction of paraquat exposure and toxicity in clinically ill poisoned patients: A model based approach.Br. J. Clin. Pharmacol.201478485586610.1111/bcp.12389 24697850
    [Google Scholar]
  60. IbrahimF.W. ZainudinU.N. LatifA.M. HamidA. Neuroprotective effects of ethyl acetate extract of Zingiber zerumbet (L.) smith against oxidative stress on paraquat-induced parkinsonism in rats.Sains Malays.201847102337234710.17576/jsm‑2018‑4710‑10
    [Google Scholar]
  61. BishnoiM. ChopraK. KulkarniS.K. Involvement of adenosinergic receptor system in an animal model of tardive dyskinesia and associated behavioural, biochemical and neurochemical changes.Eur. J. Pharmacol.20065521-3556610.1016/j.ejphar.2006.09.010 17064683
    [Google Scholar]
  62. CamposF.L. CarvalhoM.M. CristovãoA.C. Rodent models of Parkinson’s disease: Beyond the motor symptomatology.Front. Behav. Neurosci.2013717510.3389/fnbeh.2013.00175 24324416
    [Google Scholar]
  63. LubrichC. GieslerP. KippM. Motor behavioral deficits in the cuprizone model: Validity of the rotarod test paradigm.Int. J. Mol. Sci.202223191134210.3390/ijms231911342 36232643
    [Google Scholar]
  64. LeemY.H. ParkJ.S. ParkJ.E. KimD.Y. KimH.S. Neurogenic effects of rotarod walking exercise in subventricular zone, subgranular zone, and substantia nigra in MPTP-induced Parkinson’s disease mice.Sci. Rep.20221211054410.1038/s41598‑022‑14823‑5 35732806
    [Google Scholar]
  65. HammR.J. PikeB.R. O’DellD.M. LyethB.G. JenkinsL.W. The rotarod test: An evaluation of its effectiveness in assessing motor deficits following traumatic brain injury.J. Neurotrauma199411218719610.1089/neu.1994.11.187 7932797
    [Google Scholar]
  66. MazzoniP. ShabbottB. CortésJ.C. Motor control abnormalities in Parkinson’s disease.Cold Spring Harb. Perspect. Med.201226a00928210.1101/cshperspect.a009282 22675667
    [Google Scholar]
  67. GoyalR. Practical in pharmacology.5th edAhmedabadB. S. Shah Prakashan2005
    [Google Scholar]
  68. SgroiS. Kaelin-LangA. Capper-LoupC. Spontaneous locomotor activity and L-DOPA-induced dyskinesia are not linked in 6-OHDA parkinsonian rats.Front. Behav. Neurosci.2014833110.3389/fnbeh.2014.00331 25324746
    [Google Scholar]
  69. WuL. TianY.Y. ShiJ.P. Inhibition of endoplasmic reticulum stress is involved in the neuroprotective effects of candesartan cilexitil in the rotenone rat model of Parkinson’s disease.Neurosci. Lett.2013548505510.1016/j.neulet.2013.06.008 23774475
    [Google Scholar]
  70. DewsP.B. The measurement of the influence of drugs on voluntary activity in mice.Br. J. Pharmacol. Chemother.195381464810.1111/j.1476‑5381.1953.tb00749.x
    [Google Scholar]
  71. PrabhakarS. SarafM.K. BanikA. Bacopa monniera selectively attenuates suppressed superoxide dismutase activity in diazepam induced amnesic mice.Ann. Neurosci.201118181310.5214/ans.0972.7531.1118104
    [Google Scholar]
  72. ReddyD.S. KulkarniS.K. Possible role of nitric oxide in the nootropic and antiamnesic effects of neurosteroids on aging- and dizocilpine-induced learning impairment.Brain Res.1998799221522910.1016/S0006‑8993(98)00419‑3 9675286
    [Google Scholar]
  73. DunhamNW MiyaTS A note on a simple apparatus for detecting neurological deficit in rats and mice J Am Pharm Assoc 1957 46208910.1002/jps.3030460322
    [Google Scholar]
  74. AbidM. HrishikeshavanH.J. AsadM. Pharmacological evaluation of Pachyrrhizus erosus (L) seeds for central nervous system depressant activity.Indian J. Physiol. Pharmacol.2006502143151 17051733
    [Google Scholar]
  75. KulkarniS. Handbook of experimental pharmacology. Dehli: Vallabh prakashan1987
    [Google Scholar]
  76. BagewadiH. Evaluation of antiparkinsonian activity of Elaeocarpus ganitrus on Haloperidol induced Parkinson’s disease in mice.Int. J. Basic Clin. Pharmacol.201541110.5455/2319‑2003.ijbcp20150218
    [Google Scholar]
  77. HoffmanD.C. DonovanH. Catalepsy as a rodent model for detecting antipsychotic drugs with extrapyramidal side effect liability.Psychopharmacology1995120212813310.1007/BF02246184 7480543
    [Google Scholar]
  78. HaddadiR. BrooshghalanE.S. FarajniyaS. Short-term treatment with silymarin improved 6-ohda-induced catalepsy and motor imbalance in hemi-parkisonian rats.Adv. Pharm. Bull.20155446346910.15171/apb.2015.063
    [Google Scholar]
  79. NosraniA.E. TamtajiO.R. AlibolandiZ. Neuroprotective effects of probiotics bacteria on animal model of Parkinson’s disease induced by 6-hydroxydopamine: A behavioral, biochemical, and histological study.J. Immunoassay Immunochem.202142210612010.1080/15321819.2020.1833917 33078659
    [Google Scholar]
  80. GuptaD. JulkaA. JainS. Optimized cuttlefish algorithm for diagnosis of Parkinson’s disease.Cogn. Syst. Res.201852364810.1016/j.cogsys.2018.06.006
    [Google Scholar]
  81. AhmadS. ZahiruddinS. ParveenB. Indian medicinal plants and formulations and their potential against COVID-19–preclinical and clinical research.Front. Pharmacol.20211157897010.3389/fphar.2020.578970 33737875
    [Google Scholar]
  82. WahiA. NagpalR. ThotaA. DevS. JainP. Application of phytodrug delivery in various therapeutic applications for neurodegenerative diseases.In: Novel Phytopharmaceutical for Management of Disorders.Boca Raton, FLCRC Press202413616410.1201/9781003292692‑6
    [Google Scholar]
  83. ChaudharyS. KumaranS.S. GoyalV. Frontal lobe metabolic alterations characterizing Parkinson’s disease cognitive impairment.Neurol. Sci.20214231053106410.1007/s10072‑020‑04626‑9 32729012
    [Google Scholar]
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