Abstract
Parkinson’s disease (PD) is slowly developing neurodegenerative disorder associated with gradual decline in cerebration and laboriousness to perform routine piece of work. PD imposed a social burden on society through higher medical cost and by loss of social productivity in current era. The available treatment options are expensive and associated with serious adverse effect after long term use. Therefore, there is a critical clinical need to develop alternative pharmacotherapies from natural sources to prevent and cure the pathological hall marks of PD with minimal cost. Our study aimed to scrutinize the antiparkinsonian potential of curcuminoids-rich extract and its binary and ternary inclusion complexes. In healthy rats, 1 mg/kg haloperidol daily intraperitoneally, for 3 weeks was used to provoke Parkinsonism like symptoms except control group. Curcuminoids rich extract, binary and ternary inclusion complexes formulations 15–30 mg/kg, L-dopa and carbidopa (100 + 25 mg/kg) were orally administered on each day for 3 weeks. Biochemical, histopathological and RT-qPCR analyses were conducted after neurobehavioral observations. Findings of current study indicated that all curcuminoids formulations markedly mitigated the behavioral abnormalities, recovered the level of antioxidant enzymes, acetylcholinesterase inhibitory activity and neurotransmitters. Histological analysis revealed that curcuminoids supplements stabilized the neuronal loss, pigmentation and Lewy bodies’ formation. The mRNA expressions of neuro-inflammatory and specific PD pathological biomarkers were downregulated by treatment with curcuminoids formulations. Therefore, it is suggested that these curcuminoids rich extract, binary and ternary supplements should be considered as promising therapeutic agents in development of modern anti-Parkinson’s disease medications.
Similar content being viewed by others
Data availability
Data will be provided upon request.
References
Abdel-Salam OM, El-Shamarka ME-S, Salem NA, Gaafar AE-DM (2012) Effects of Cannabis sativa extract on haloperidol-induced catalepsy and oxidative stress in the mice. EXCLI J 11:45. https://doi.org/10.1007/s00580-013-1745-1
Aggarwal BB, Kumar A, Bharti AC (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23:363–398. https://doi.org/10.1201/9780203025901.ch36
Ali M, Saleem U, Anwar F, Imran M, Nadeem H, Ahmad B, Ali T, Ismail T (2021) Screening of synthetic isoxazolone derivative role in alzheimer’s disease: computational and pharmacological approach. Neurochem Res 46:905–920. https://doi.org/10.1007/s11064-021-03229-w
Aruna K, Rajeswari PDR, Sankar SR (2017) The effect of Oxalis corniculata extract against the behavioral changes induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) in mice. J Appl Pharm Sci 7:148–153. https://doi.org/10.7324/japs.2017.70324
Bais S, Gill N, Kumar N (2015) Neuroprotective effect of Juniperus communis on chlorpromazine induced Parkinson disease in animal model. Chin J Biol 2015. https://doi.org/10.1155/2015/542542
Ball N, Teo W-P, Chandra S, Chapman J (2019) Parkinson’s disease and the environment. Front Neurol 10:218. https://doi.org/10.3389/fneur.2019.00218
Barreto GE, Iarkov A, Moran VE (2015) Beneficial effects of nicotine, cotinine and its metabolites as potential agents for Parkinson’s disease. Front Aging Neurosci 6:340. https://doi.org/10.3389/fnagi.2014.00340
Bhangale JO, Acharya SR (2016) Anti-Parkinson activity of petroleum ether extract of Ficus religiosa (L.) leaves. Adv Pharmacol 2016. https://doi.org/10.1111/j.1460-9568.2006.04812.x
Brown RE, Corey SC, Moore AK (1999) Differences in measures of exploration and fear in MHC-congenic C57BL/6J and B6-H-2K mice. Behav Genet 29:263–271. https://doi.org/10.1016/s0166-4328(03)00093-7
Carrey N, Mcfadyen MP, Brown RE (2000) Effects of subchronic methylphenidate hydrochloride administration on the locomotor and exploratory behavior of prepubertal mice. J Child Adolesc Psychopharmacol 10:277–286. https://doi.org/10.1089/cap.2000.10.277
Chauhdary Z, Saleem U, Ahmad B, Shah S, Shah MA (2019) Neuroprotective evaluation of Tribulus terrestris L. in aluminum chloride induced Alzheimer’s disease. Pak J Pharm Sci 32:805–816. https://doi.org/10.1021/acsomega.0c03375
Chitra V, Manasa K, Mythili A, Tamilanban T, Gayathri K (2017) Effect of hydroalcoholic extract of achyranthes aspera on haloperidolinduced parkinson's disease in wistar rats. Asian J Pharm Clin Res 10:318–321. https://doi.org/10.22159/ajpcr.2017.v10i9.19285
Coura CO, Souza RB, Rodrigues JA, Vanderlei EdeS, de Araújo IW, Ribeiro NA, Frota AF, Ribeiro KA, Chaves HV, Pereira KM, da Cunha RM, Bezerra MM, Benevides NM (2015) Mechanisms involved in the anti-inflammatory action of a polysulfated fraction from Gracilaria cornea in rats. PloS one 10:e0119319. https://doi.org/10.1371/journal.pone.0119319
Cummings BJ, Engesser-Cesar C, Cadena G, Anderson AJ (2007) Adaptation of a ladder beam walking task to assess locomotor recovery in mice following spinal cord injury. Behav Brain Res 177:232–241. https://doi.org/10.1016/j.bbr.2006.11.042
Darvesh AS, Carroll RT, Bishayee A, Novotny NA, Geldenhuys WJ, Van Der Schyf CJ (2012) Curcumin and neurodegenerative diseases: a perspective. Expert Opin Investig Drugs 21:1123–1140. https://doi.org/10.1517/13543784.2012.693479
Deacon RM (2013) Measuring motor coordination in mice. J Vis Exp e2609. https://doi.org/10.3791/2609
Dexter DT, Jenner P (2013) Parkinson disease: from pathology to molecular disease mechanisms. Free Radic Biol Med 62:132–144. https://doi.org/10.1016/j.freeradbiomed.2013.01.018
Doke RR, Lakhdive KV (nd) Restorative potential of curcumin in Parkinson’s disease. Inventi Journals. https://doi.org/10.1201/9780203508596-79
Elliott P, Close SP, Walsh DM, Hayes AG, Marriott AS (1990) Neuroleptic-induced catalepsy as a model of Parkinson’s disease I. Effect of dopaminergic agents. J Neural Transm 2:79–89. https://doi.org/10.1007/bf02260896
Gould S, Scott RC (2005) 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD): a toxicology review. Food Chem Toxicol 43:1451–1459. https://doi.org/10.1016/j.fct.2005.03.007
Hamed MA, Mohammed MA, Aboul Naser AF, Matloub AA, Fayed DB, Ali SA, Khalil WKB (2019) Optimization of curcuminoids extraction for evaluation against Parkinson’s disease in rats. J Biol Act Prod Nat 9:335–351. https://doi.org/10.1080/22311866.2019.1698317
Han Y, Hou Z, Zhang X, Yan K, Liang Z, He Q (2022) Important changes in germination, seedling tolerance, and active components content due to drought stress on three licorice (Glycyrrhiza) species. Ind Crop Prod 175:114240. https://doi.org/10.1016/j.indcrop.2021.114240
Hira S, Saleem U, Anwar F, Raza Z, Rehman AU, Ahmad B (2020) In silico study and pharmacological evaluation of Eplerinone as an Anti-Alzheimer’s drug in STZ-induced Alzheimer’s disease model. ACS Publications 5:13973–13983. https://doi.org/10.1021/acsomega.0c01381
Hira S, Saleem U, Anwar F, Sohail MF, Raza Z, Ahmad B (2019) β-Carotene: a natural compound improves cognitive impairment and oxidative stress in a mouse model of streptozotocin-induced Alzheimer’s disease. Biomolecules 9:441. https://doi.org/10.3390/biom9090441
Hummon AB, Lim SR, Difilippantonio MJ, Ried T (2007) Isolation and solubilization of proteins after TRIzol® extraction of RNA and DNA from patient material following prolonged storage. Biotechniques 42:467–472. https://doi.org/10.2144/000112401
Ishola IO, Akinyede AA, Adeluwa TP, Micah C (2018) Novel action of vinpocetine in the prevention of paraquat-induced parkinsonism in mice: involvement of oxidative stress and neuroinflammation. Metab Brain Dis 33:1493–1500. https://doi.org/10.1007/s11011-018-0256-9
Jagatha B, Mythri RB, Vali S, Bharath MMS (2008) Curcumin treatment alleviates the effects of glutathione depletion in vitro and in vivo: therapeutic implications for Parkinson’s disease explained via in silico studies. Free Radic Biol Med 44:907–917. https://doi.org/10.1016/j.freeradbiomed.2007.11.011
Jiang H, Zhang XJ (2008) Acetylcholinesterase and apoptosis. A novel perspective for an old enzyme. FEBS J 275:612–617. https://doi.org/10.1111/j.1742-4658.2007.06236.x
Klapdor K, Dulfer BG, Hammann A, Van Der Staay FJ (1997) A low-cost method to analyse footprint patterns. J Neurosci Methods 75:49–54. https://doi.org/10.1016/s0165-0270(97)00042-3
Koprich JB, Reske-Nielsen C, Mithal P, Isacson OJJON (2008) Neuroinflammation mediated by IL-1β increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's disease. J Neuroinflammation 5:1–12. https://doi.org/10.1186/1742-2094-5-8
Lakshmi B, Sudhakar M, Prakash KS (2015) Protective effect of selenium against aluminum chloride-induced Alzheimer’s disease: behavioral and biochemical alterations in rats. Biol Trace Elem Res 165:67–74. https://doi.org/10.1007/s12011-015-0229-3
Lang AE, Espay AJ (2018) Disease modification in Parkinson’s disease: current approaches, challenges, and future considerations. Mov Disord 33:660–677. https://doi.org/10.1002/mds.27360
Lateh L, Yuenyongsawad S, Chen H, Panichayupakaranant P (2019) A green method for preparation of curcuminoid-rich Curcuma longa extract and evaluation of its anticancer activity. Pharmacogn Mag 15:730. https://doi.org/10.4103/pm.pm_162_19
Leal MC, Casabona JC, Puntel M, Pitossi FJ (2013) Interleukin-1β and tumor necrosis factor-α: reliable targets for protective therapies in Parkinson’s disease? Front Cell Neurosci 7:53. https://doi.org/10.3389/fncel.2013.00053
Li S, Yuan W, Deng G, Wang P, Yang P, Aggarwal B (2011) Chemical composition and product quality control of turmeric (Curcuma longa L.). Pharmaceutical Crops 2:28–54. https://doi.org/10.2174/2210290601102010028
Marsili L, Marconi R, Colosimo C (2017) Treatment strategies in early Parkinson’s disease. Int Rev Neurobiol 132:345–360. https://doi.org/10.1016/bs.irn.2017.01.002
Nascimento-Ferreira I, Nobrega C, Vasconcelos-Ferreira A, Onofre I, Albuquerque D, Aveleira C, Hirai H, Deglon N, Pereira De Almeida L (2013) Beclin 1 mitigates motor and neuropathological deficits in genetic mouse models of Machado-Joseph disease. Brain 136:2173–2188. https://doi.org/10.1093/brain/awt144
Nemani VM, Lu W, Berge V, Nakamura K, Onoa B, Lee MK, Chaudhry FA, Nicoll RA, Edwards RH (2010) Increased expression of α-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65:66–79. https://doi.org/10.1016/j.neuron.2009.12.023
Pal P, Ghosh A (2018) Antioxidant, anti-alzheimer and anti-parkinson activity of Artemisia nilagirica leaves with flowering tops. J Pharm Biosci 12–23. https://doi.org/10.20510/ukjpb/6/i2/173536
Parambi DGT, Saleem U, Shah MA, Anwar F, Ahmad B, Manzar A, Itzaz A, Harilal S, Uddin MS, Kim H, Mathew B (2020) Exploring the therapeutic potentials of highly selective oxygenated chalcone based MAO-B inhibitors in a haloperidol-induced murine model of Parkinson’s disease. Neurochem Res 45:2786–2799. https://doi.org/10.1007/s11064-020-03130-y
Rajasankar S, Manivasagam T, Surendran S (2009) Ashwagandha leaf extract: a potential agent in treating oxidative damage and physiological abnormalities seen in a mouse model of Parkinson’s disease. Neurosci Lett 454:11–15. https://doi.org/10.1016/j.neulet.2009.02.044
Saleem U, Amin S, Ahmad B, Azeem H, Anwar F, Mary S (2017) Acute oral toxicity evaluation of aqueous ethanolic extract of Saccharum munja Roxb. roots in albino mice as per OECD 425 TG. Toxicol Rep 4:580–585. https://doi.org/10.1016/j.toxrep.2017.10.005
Saleem U, Raza Z, Anwar F, Ahmad B, Hira S, Ali T (2019) Experimental and computational studies to characterize and evaluate the therapeutic effect of albizia lebbeck (L.) seeds in alzheimer’s disease. Medicina 55:184. https://doi.org/10.3390/medicina55050184
Saleem U, Gull Z, Saleem A, Shah MA, Akhtar MF, Anwar F, Ahmad B, Panichayupakaranant P (2021a) Appraisal of anti-Parkinson activity of rhinacanthin-C in haloperidol-induced parkinsonism in mice: a mechanistic approach. J Food Biochem 45:e13677. https://doi.org/10.1111/jfbc.13677
Saleem U, Shehzad A, Shah S, Raza Z, Shah MA, Bibi S, Chauhdary Z, Ahmad B (2021b) Antiparkinsonian activity of Cucurbita pepo seeds along with possible underlying mechanism. Metab Brain Dis 36:1231–1251. https://doi.org/10.1007/s11011-021-00707-6
Sanawar M, Saleem U, Anwar F, Nazir S, Akhtar MF, Ahmad B, Ismail TJIJON (2020) Investigation of anti-Parkinson activity of dicyclomine. Int J Neurosci 1–14. https://doi.org/10.1080/00207454.2020.1815732
Sanberg PR, Martinez R, Shytle RD, Cahill DW (1996) The catalepsy test. In: Motor activity and movement disorders. Springer, pp 197–211. https://doi.org/10.1007/978-1-59259-469-6_7
Shishodia S, Sethi G, Aggarwal BB (2005) Curcumin: getting back to the roots. Ann N Y Acad Sci 1056:206–217. https://doi.org/10.1196/annals.1352.010
Singh PK, Kotia V, Ghosh D, Mohite GM, Kumar A, Maji SK (2013) Curcumin modulates α-synuclein aggregation and toxicity. ACS Chem Neurosci 4:393–407. https://doi.org/10.1021/cn3001203
Skinner JW, Christou EA, Hass CJ (2019) Lower extremity muscle strength and force variability in persons with Parkinson disease. J Neurol Phys Ther 43:56–62. https://doi.org/10.1097/npt.0000000000000244
Srivastav S, Fatima M, Mondal AC (2017) Important medicinal herbs in Parkinson’s disease pharmacotherapy. Biomed Pharmacother 92:856–863. https://doi.org/10.1016/j.biopha.2017.05.137
Surendran S, Rajasankar S (2010) Parkinson’s disease: oxidative stress and therapeutic approaches. Neurol Sci 31:531–540. https://doi.org/10.1007/s10072-010-0245-1
Tillerson JL, Miller GW (2003) Grid performance test to measure behavioral impairment in the MPTP-treated-mouse model of parkinsonism. J Neurosci Methods 123:189–200. https://doi.org/10.1016/s0165-0270(02)00360-6
Wang X-S, Zhang Z-R, Zhang M-M, Sun M-X, Wang W-W, Xie C-L (2017) Neuroprotective properties of curcumin in toxin-base animal models of Parkinson’s disease: a systematic experiment literatures review. BMC Complement Med Ther 17:1–10. https://doi.org/10.1016/s0165-0270(02)00360-6
Yallapu MM, Jaggi M, Chauhan SC (2012) Curcumin nanoformulations: a future nanomedicine for cancer. Drug Discov Today 17:71–80. https://doi.org/10.1016/j.drudis.2011.09.009
Author information
Authors and Affiliations
Contributions
US, MAS and PP designed the research concept. SK, ZC and FA performed the experiment and collected the results. IA, AOA, TASB and AEA analyzed the results and prepared the manuscript. ROK, TASB, MF, IA, AOA, AEA, CVL and PP revised and edited the manuscript.
Corresponding authors
Ethics declarations
Ethical statement
Animals studies were conducted according to all national and international ethical guidelines required for animal use and care.
Consent to participate
All authors declared willingness to participate.
Publication consent
It is declared by all authors to publish.
Conflict of interest
All authors declared no conflict of interest.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Saleem, U., Khalid, S., Chauhdary, Z. et al. The curative and mechanistic acumen of curcuminoids formulations against haloperidol induced Parkinson’s disease animal model. Metab Brain Dis 38, 1051–1066 (2023). https://doi.org/10.1007/s11011-022-01122-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-022-01122-1