Skip to main content

In Silico and In Vivo Studies on Quercetin as Potential Anti-Parkinson Agent

  • Conference paper
  • First Online:
GeNeDis 2018

Abstract

Parkinson’s disease (PD) is a major cause of morbidity and mortality among older individuals. Several researchers have suggested that iron chelators which cross the blood-brain barrier (BBB) might have clinical efficacy in treating PD. Therefore, efforts are made not only in order to improve the effect of L-dopa but also to introduce drugs which provide anti-parkinsonian and neuroprotective effects. In this study, quercetin, a flavonoid, exhibited noticeable neuroprotective effects via iron induced-oxidative stress-dependent apoptotic pathways. Our results suggested that quercetin significantly decreased the catalepsy and exhibited neuroprotective effects in rotenone-induced Parkinson. A model of rotenone-induced Parkinsonism in rats produced the decrease in glutathione, SOD, catalase, and serum iron concentration and the increase in H2O2 and lipid peroxidation activity. Quercetin efficiently halted the deleterious toxic effects of L-dopa, revealing normalization of catalepsy and rotarod score, in addition to amelioration of neurochemical parameters, indicating benefit of both symptomatic and neuroprotective therapies. In silico molecular docking studies have also shown that quercetin could be an ideal potential drug target for aromatic L-amino acid decarboxylase and human catechol-O-methyltransferase. In conclusion, quercetin possesses strong iron-chelating abilities and could be recommended as a disease-modifying therapy when administered in combination with L-dopa, early on in the course of Parkinson’s disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aguilera G, Colín-González AL, Rangel-López E, Chavarría A, Santamaría A (2018) Redox signaling, neuroinflammation, and neurodegeneration. Antioxid Redox Signal 28(18):1626–1651

    Article  CAS  PubMed  Google Scholar 

  • Boyina HK, Jerald MK, Bharatraj DK, Diwan PV (2018) Influence of fisetin combined with hesperidin on chronic mild hyperhomocysteinemia induced cognitive dysfunction and oxidative stress in wistar rats. Pharma Nutrition 6(3):125–136

    Article  Google Scholar 

  • Castañeda-Arriaga R, Pérez-González A, Reina M, Alvarez-Idaboy JR, Galano A (2018) Comprehensive investigation on the antioxidant and pro-oxidant effects of phenolic compounds: a double-edged sword in the context of oxidative stress? J Phys Chem B 122(23):6198–6214

    Article  PubMed  Google Scholar 

  • Cenci MA, Crossman AR (2018) Animal models of l-dopa-induced dyskinesia in Parkinson’s disease. Mov Disord 33(6):889–899

    Article  CAS  PubMed  Google Scholar 

  • Chauhan A, Jeans AF (2015) Is Parkinson’s disease truly a prion-like disorder? An appraisal of current evidence. Neurol Res Int 2015:345285

    PubMed  PubMed Central  Google Scholar 

  • Costall B, Naylor R (1974) On catalepsy and catatonia and the predictability of the catalepsy test for neuroleptic activity. Psychopharmacologia 34(3):233–241

    Article  CAS  PubMed  Google Scholar 

  • El-Horany HE, El-latif RNA, ElBatsh MM, Emam MN (2016) Ameliorative effect of quercetin on neurochemical and behavioral deficits in rotenone rat model of Parkinson’s disease: modulating autophagy (quercetin on experimental Parkinson’s disease). J Biochem Mol Toxicol 30(7):360–369

    Article  CAS  PubMed  Google Scholar 

  • Erboga M, Aktas C, Erboga ZF, Donmez YB, Gurel A (2015) Quercetin ameliorates methotrexate-induced renal damage, apoptosis and oxidative stress in rats. Ren Fail 37(9):1492–1497

    Google Scholar 

  • Ghiglieri V, Calabrese V, Calabresi P (2018) Alpha-Synuclein: from early synaptic dysfunction to neurodegeneration. Front Neurol 9:295

    Article  PubMed  PubMed Central  Google Scholar 

  • Gould FD, Gross A, German RZ, Richardson JR (2018) Evidence of oropharyngeal dysfunction in feeding in the rat rotenone model of Parkinson’s disease. Parkinson’s Disease.11;2018:6537072

    Google Scholar 

  • Gowthami N, Sunitha B, Kumar M, Prasad TK, Gayathri N, Padmanabhan B, Bharath MS (2018) Mapping the protein phosphorylation sites in human mitochondrial complex I (NADH: ubiquinone oxidoreductase): a bioinformatics study with implications for brain aging and neurodegeneration. J Chem Neuroanat 95:13–28

    Article  PubMed  Google Scholar 

  • Hemanth Kumar B, Arun Reddy R, Mahesh Kumar J, Dinesh Kumar B, Diwan PV (2016) Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia. Can J Physiol Pharmacol 95(1):32–42

    Article  PubMed  Google Scholar 

  • Hemanth Kumar B, Dinesh Kumar B, Diwan PV (2017) Hesperidin, a citrus flavonoid, protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats. Pharm Biol 55(1):146–155

    Article  CAS  PubMed  Google Scholar 

  • Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. Journal of Neurology, Neurosurgery & Psychiatry 79(4):368–376

    Article  CAS  Google Scholar 

  • Jeon SJ, Kim MO, Ali-Shah F, Koh PO (2017) Quercetin attenuates the injury-induced reduction of γ-enolase expression in a middle cerebral artery occlusion animal model. Lab Anim Res 33(4):308

    Google Scholar 

  • Kabel AM, Omar MS, Alhadhrami A, Alharthi SS, Alrobaian MM (2018) Linagliptin potentiates the effect of l-dopa on the behavioural, biochemical and immunohistochemical changes in experimentally-induced parkinsonism: role of toll-like receptor 4, TGF-β1, NF-κB and glucagon-like peptide 1. Physiol Behav 188:108–118

    Article  CAS  PubMed  Google Scholar 

  • Keddy PG, Dunlop K, Warford J, Samson ML, Jones QR, Rupasinghe HP, Robertson GS (2012) Neuroprotective and anti-inflammatory effects of the flavonoid-enriched fraction AF4 in a mouse model of hypoxic-ischemic brain injury. PLoS One 7(12):e51324

    Google Scholar 

  • Kelly MA, Rubinstein M, Phillips TJ, Lessov CN, Burkhart-Kasch S, Zhang G, Bunzow JR, Fang Y, Gerhardt GA, Grandy DK, Low MJ (1998) Locomotor activity in D2 dopamine receptor-deficient mice is determined by gene dosage, genetic background, and developmental adaptations. J Neurosci 18(9):3470–3479

    Google Scholar 

  • Li C, Tang B, Feng Y, Tang F, Pui-Man Hoi M, Su Z, Ming-Yuen Lee S (2018) Pinostrobin exerts neuroprotective actions in neurotoxin-induced Parkinson’s disease models through Nrf2 induction. J Agric Food Chem 66(31):8307–8318

    Article  PubMed  Google Scholar 

  • Michel PP, Hirsch EC, Hunot S (2016) Understanding dopaminergic cell death pathways in Parkinson disease. Neuron 90(4):675–691

    Article  CAS  PubMed  Google Scholar 

  • Ruddarraju RR, Kiran G, Murugulla AC, Maroju R, Prasad DK, Kumar BH, Bakshi V, Reddy NS (2019) Design, synthesis and biological evaluation of theophylline containing variant acetylene derivatives as α-amylase inhibitors. Bioorg Chem 92:103120

    Google Scholar 

  • Sarubbo F, Esteban S, Miralles A, Moranta D (2018) Effects of resveratrol and other polyphenols on Sirt1: relevance to brain function during aging. Curr Neuropharmacol 16(2):126–136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma N, Nehru B (2013) Beneficial effect of vitamin E in rotenone induced model of PD: behavioural, neurochemical and biochemical study. Exp Neurobiol 22(3):214–223

    Article  PubMed  PubMed Central  Google Scholar 

  • Sharma S, Kumar P, Deshmukh R (2018) Neuroprotective potential of spermidine against rotenone induced Parkinson’s disease in rats. Neurochem Int 116:104–111

    Article  CAS  PubMed  Google Scholar 

  • Shi GJ, Li Y, Cao QH, Wu HX, Tang XY, Gao XH, Yu JQ, Chen Z, Yang Y (2019) In vitro and in vivo evidence that quercetin protects against diabetes and its complications: A systematic review of the literature. Biomed Pharmacother 109:1085–1099

    Google Scholar 

  • Surmeier DJ (2018) Determinants of dopaminergic neuron loss in Parkinson’s disease. FEBS J 285:3657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan X, Uronen R-L, Huttunen HJ (2018) The interaction of α-synuclein and Tau: a molecular conspiracy in neurodegeneration? Semin Cell Dev Biol.9:S1084-9521(17)30389-0

    Google Scholar 

Download references

Acknowledgments

We thank Dr. P. Rajeshwar Reddy (Chairman, Anurag Group of Institutions) and Dr. Prakash V Diwan (Director, Anurag Group of Institutions) for providing research facilities to carry out this work.

Conflict of Interest

The authors declare no conflict of interest.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Boyina, H.K. et al. (2020). In Silico and In Vivo Studies on Quercetin as Potential Anti-Parkinson Agent. In: Vlamos, P. (eds) GeNeDis 2018. Advances in Experimental Medicine and Biology, vol 1195. Springer, Cham. https://doi.org/10.1007/978-3-030-32633-3_1

Download citation

Publish with us

Policies and ethics