Skip to main content
Log in

Neuroprotective effects of hydro-alcoholic extract of Eclipta alba against 1-methyl-4-phenylpyridinium-induced in vitro and in vivo models of Parkinson’s disease

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Pathogenesis of Parkinson’s disease (PD) specifically involves the degeneration of dopaminergic neurons in the substantia nigra region, which mainly begun with the overwhelmed oxidative stress and neuroinflammation. Considering the antioxidant and other pharmacological properties, Eclipta alba needs to be exploited for its possible neuroprotective efficacy against PD and other neurological disorders. Therefore, the current study was conducted to exemplify the remedial effects of hydro-alcoholic extract of E. alba (EA-MEx) against MPP+-elicited in vitro and in vivo PD models. SH-SY5Y, a neuroblastoma cell culture and male Wistar rats were used to impersonate the hallmarks of PD. Qualitative and quantitative analyses of EA-MEx revealed the presence of quercetin, ellagic acid, catechin, kaempferol, and epicatechin at varying concentrations. EA-MEx was found to deliver considerable protection against MPP+-induced oxidative damages in SH-SY5Y cells. Furthermore, in vivo study also supported the neuroprotective efficacy of EA-MEx, with significant mitigation of behavioral deficits induced by intrastriatal injection of MPP+. Furthermore, the disturbed levels of cellular antioxidant machinery have been significantly improved with the pre-treatment of EA-MEx. Mechanistically, the expression of α-synuclein, tyrosine hydroxylase, and mortalin were also found to be improved with the prior treatment of EA-MEx. Hence, the study suggests Eclipta alba as a suitable candidate for the development of better neuropathological therapeutics.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6.
Fig. 7.
Fig. 8.

Similar content being viewed by others

Data availability

All datasets produced for this study are included in the manuscript.

Abbreviations

DAergic:

Dopaminergic

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

Dimethyl sulfoxide

EA-MEx:

95% hydro-alcoholic extract of Eclipta alba

EDTA:

Ethylenediaminetetraacetic acid

FBS:

Fetal bovine serum

GSH:

Reduced glutathione

H2O2 :

Hydrogen peroxide

IC50 :

50% inhibitory concentration

MgCl2 :

Magnesium chloride

MPP+ :

1-Methyl-4-phenylpyridinium

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MTT:

3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

6-OHDA:

6-Hydroxydopamine

PBST:

Phosphate buffer saline/Triton X-100

PD:

Parkinson’s disease

RT-PCR:

Reverse transcriptase polymerase chain reaction

TRI:

Trizol

UPLC:

Ultrapressure liquid chromatography

References

  • Aguirre-Vidal Y, Montes S, Tristan-López L, Anaya-Ramos L, Teiber J, Ríos C, Baron-Flores V, Monroy-Noyola A (2015) The neuroprotective effect of lovastatin on MPP+ induced neurotoxicity is not mediated by PON2. Neurotoxicology 48:166–170

    CAS  Google Scholar 

  • Annepu J, Ravindranath V (2000) 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced complex I inhibition is reversed by disulfide reductant, dithiothreitol in mouse brain. Neurosci Lett 289(3):209–212

    CAS  Google Scholar 

  • Aslan A, Gok O, Beyaz S, Arslan E, Erman O, Ağca CA (2020) The preventive effect of ellagic acid on brain damage in rats via regulating of Nrf-2, NF-kB, and apoptotic pathway. J Food Biochem 2020:e13217

    Google Scholar 

  • Balke D, Tatenhorst L, Dambeck V, Ribas VT, Vahsen BF, Michel U, Bähr M, Lingor P (2020) AAV-mediated expression of dominant-negative ULK1 increases neuronal survival and enhances motor performance in the MPTP mouse model of Parkinson’s disease. Mol Neurobiol 57(2):685–697

    CAS  Google Scholar 

  • Baluchnejadmojarad T, Rabiee N, Zabihnejad S, Roghani M (2017) Ellagic acid exerts protective effect in intrastriatal 6-hydroxydopamine rat model of Parkinson’s disease: possible involvement of ERβ/Nrf2/HO-1 signaling. Brain Res 1662:23–30

    CAS  Google Scholar 

  • Barc S, Page G, Barrier L, Garreau L, Guilloteau D, Fauconneau B, Chalon S (2002) Relevance of different striatal markers in assessment of the MPP+ induced dopaminergic nigrostriatal injury in rat. J Neurochem 80(3):365–374

    CAS  Google Scholar 

  • Beal MF (2009) Therapeutic approaches to mitochondrial dysfunction in Parkinson’s disease. Parkinsonism Relat D 15:189–194

    Google Scholar 

  • Bhaskar M, Chintamaneni M (2014) Withania somnifera and Eclipta alba ameliorate oxidative stress induced mitochondrial dysfunction in an animal model of Alzheimer’s disease. Am J Phytomed Clin Ther 2:140–152

    Google Scholar 

  • Bhatia G, Dhuna V, Dhuna K, Kaur M, Singh J (2017) Bacopa monnieri extracts prevent hydrogen peroxide-induced oxidative damage in a cellular model of neuroblastoma IMR32 cells. Chin J Nat Med 15(11):834–846

    CAS  Google Scholar 

  • Castelli V, Melani F, Ferri C, d’Angelo M, Catanesi M, Grassi D, Benedetti E, Giordano A, Cimini A, Desideri G (2020) Neuroprotective activities of bacopa, lycopene, astaxanthin, and vitamin B12 combination on oxidative stress-dependent neuronal death. J Cell Biochem 121:4862–4869. https://doi.org/10.1002/jcb.29722

    Article  CAS  Google Scholar 

  • Chen M, Wang T, Yue F, Li X, Wang P, Li Y, Chan P, Yu S (2015) Tea polyphenols alleviate motor impairments, dopaminergic neuronal injury, and cerebral α-synuclein aggregation in MPTP-intoxicated parkinsonian monkeys. Neuroscience 286:383–392

    CAS  Google Scholar 

  • Cheruku SP, Ramalingayya GV, Chamallamudi MR, Biswas S, Nandakumar K, Nampoothiri M, Gourishetti K, Kumar N (2018) Catechin ameliorates doxorubicin-induced neuronal cytotoxicity in in vitro and episodic memory deficit in in vivo in Wistar rats. Cytotechnology 70(1):245–259

    CAS  Google Scholar 

  • Chokotia LS, Vashistha P, Sironiya R, Matoli H (2013) Pharmacological activities of Eclipta alba (L.). Int J Res Dev Pharm Life Sci 2(4):499–502

    Google Scholar 

  • Cookson MR (2009) α-Synuclein and neuronal cell death. Mol Neurodegener 4:9

    Google Scholar 

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

    CAS  Google Scholar 

  • Datta K, Singh AT, Mukherjee A, Bhat B, Ramesh B, Burman AC (2009) Eclipta alba extract with potential for hair growth promoting activity. J Ethnopharmacol 124(3):450–456

    Google Scholar 

  • Deng H, Jia Y, Pan D, Ma Z (2020) Berberine alleviates rotenone-induced cytotoxicity by antioxidation and activation of PI3K/Akt signaling pathway in SH-SY5Y cells. NeuroReport 31(1):41–47

    CAS  Google Scholar 

  • Ferlazzo N, Cirmi S, Maugeri A, Russo C, Lombardo GE, Gangemi S, Calapai G, Mollace V, Navarra M (2020) Neuroprotective effect of bergamot juice in 6-OHDA-induced SH-SY5Y cell death, an in vitro model of Parkinson’s disease. Pharmaceutics 12(4):326

    CAS  Google Scholar 

  • Gandhi S, Abramov AY (2012) Mechanism of oxidative stress in neurodegeneration. Oxidative Med Cell Longev 2012:428010

    Google Scholar 

  • Glowinski J, Iversen LL (1966) Regional studies of catecholamines in the rat brain—I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J Neurochem 13:655–669

    CAS  Google Scholar 

  • Gong X, Wang H, Ye Y, Shu Y, Deng Y, He X, Lu G, Zhang S (2016) miR-124 regulates cell apoptosis and autophagy in dopaminergic neurons and protects them by regulating AMPK/mTOR pathway in Parkinson’s disease. Am J Transl Res 8(5):2127–2137

    CAS  Google Scholar 

  • Halliwell B, Gutteridge JM (2015) Free radicals in biology and medicine. Oxford University Press, USA

    Google Scholar 

  • Hansen MB, Nielsen SE, Berg K (1989) Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods 119(2):203–210

    CAS  Google Scholar 

  • Harborne JB (1998) Phytochemical methods: a guide to modern techniques of plant analysis. Champman and Hall, London

    Google Scholar 

  • Jadhav VM, Thorat RM, Kadam VJ, Salaskar KP (2009) Chemical composition, pharmacological activities of Eclipta alba. J Pharm Res 2(8):1129–1231

    Google Scholar 

  • Jaiswal N, Bhatia V, Srivastava SP, Srivastava AK, Tamrakar AK (2012) Antidiabetic effect of Eclipta alba associated with the inhibition of alpha-glucosidase and aldose reductase. Nat Prod Res 26(24):2363–2367

    CAS  Google Scholar 

  • Javed H, Meeran N, Fizur M, Azimullah S, Adem A, Sadek B, Ojha SK (2019) Plant extracts and phytochemicals targeting α-synuclein aggregation in Parkinson’s disease models. Front Pharmacol 2019:1555

    Google Scholar 

  • Jeong JS, Piao Y, Kang S, Son M, Kang YC, Du XF, Ryu J, Cho YW, Jiang HH, Oh MS, Hong SP (2018) Triple herbal extract DA-9805 exerts a neuroprotective effect via amelioration of mitochondrial damage in experimental models of Parkinson’s disease. Sci Rep 8(1):1–13

    Google Scholar 

  • Kim GH, Kim JE, Rhie SJ, Yoon S (2015) The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol 24(4):325–340

    Google Scholar 

  • Kulkarni SK (2002) Handbook of experimental pharmacology. Vallabh Prakashan, Delhi

    Google Scholar 

  • Kumar P, Singh R, Nazmi A, Lakhanpal D, Kataria H, Kaur G (2014) Glioprotective effects of Ashwagandha leaf extract against lead induced toxicity. Biomed Res Int 2014:182029

    Google Scholar 

  • Lee E, Hwang I, Park S, Hong S, Hwang B, Cho Y, Son J, Yu JW (2019) MPTP-driven NLRP3 inflammasome activation in microglia plays a central role in dopaminergic neurodegeneration. Cell Death Differ 26(2):213–228

    CAS  Google Scholar 

  • Lima FAV, Joventino IP, Joventino FP, de Almeida AC, Neves KRT, do Carmo MR, Leal LKAM, de Andrade GM, de Barros Viana GS (2017) Neuroprotective activities of Spirulina platensis in the 6-OHDA model of Parkinson’s disease are related to its anti-inflammatory effects. Neurochem Res 42(12):3390–3400

    CAS  Google Scholar 

  • Liu J, Liu W, Lu Y, Tian H, Duan C, Lu L, Gao G, Wu X, Wang X, Yang H (2018) Piperlongumine restores the balance of autophagy and apoptosis by increasing BCL2 phosphorylation in rotenone-induced Parkinson disease models. Autophagy 14(5):845–861

    CAS  Google Scholar 

  • Liu QM, Zhao HY, Zhong XK, Jiang JG (2012) Eclipta prostrata L. phytochemicals: Isolation, structure elucidation, and their antitumor activity. Food Chem Toxicol 50(11):4016–4022

    CAS  Google Scholar 

  • Liu Y, Zhang RY, Zhao J, Dong Z, Feng DY, Wu R, Shi M, Zhao G (2015) Ginsenoside Rd protects SH-SY5Y cells against 1-methyl-4-phenylpyridinium induced injury. Int J Mol Sci 16(7):14395–14408

    CAS  Google Scholar 

  • Londono C, Osorio C, Gama V, Alzate O (2012) Mortalin, apoptosis and neurodegeneration. Biomolecules 2:143–164

    CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  Google Scholar 

  • Luck H (1965) Catalase. In: Bergmeyer HU (ed) Methods of enzymatic analysis, 2nd edn. Academic Press, New York, pp 885–894

    Google Scholar 

  • Manchanda S, Mishra R, Singh R, Kaur T, Kaur G (2017) Aqueous leaf extract of Withania somnifera as a potential neuroprotective agent in sleep-deprived rats: a mechanistic study. Mol Neurobiol 54(4):3050–3061

    CAS  Google Scholar 

  • Mansoorali KP, Prakash T, Kotresha D, Prabhu K, Rao NR (2012) Cerebroprotective effect of Eclipta alba against global model of cerebral ischemia induced oxidative stress in rats. Phytomedicine 19(12):1108–1116

    CAS  Google Scholar 

  • Marrazzo P, Angeloni C, Hrelia S (2019) Combined treatment with three natural antioxidants enhances neuroprotection in a SH-SY5Y 3D culture model. Antioxidants 8(10):420

    CAS  Google Scholar 

  • Moron MS, Depierre JW, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione-S-transferase activities in rat lung and liver. BBA-Gen Sub 582:67–78

    CAS  Google Scholar 

  • Nehru B, Verma R, Khanna P, Sharma SK (2008) Behavioral alterations in rotenonemodel of Parkinson’s disease: attenuation by co-treatment of centrophenoxine. Brain Res 1201:122–127

    CAS  Google Scholar 

  • Nichols M, Zhang J, Polster BM, Elustondo PA, Thirumaran A, Pavlov EV, Robertson GS (2015) Synergistic neuroprotection by epicatechin and quercetin: activation of convergent mitochondrial signaling pathways. Neuroscience 308:75–94

    CAS  Google Scholar 

  • Ning B, Zhang Q, Wang N, Deng M, Fang Y (2019) β-Asarone regulates ER stress, and autophagy via inhibition of the PERK/CHOP/Bcl-2/Beclin-1 pathway in 6-OHDA-induced Parkinsonian Rats. Neurochem Res 44:1159–1166

    CAS  Google Scholar 

  • Paxinos G, Watson C (1998) A stereotaxic atlas of the rat brain. Academic Press, New York

    Google Scholar 

  • Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem 97:55–74

    CAS  Google Scholar 

  • Prabu K, Kanchana N, Sadiq AM (2011) Hepatoprotective effect of Eclipta alba on paracetamol induced liver toxicity in rats. J Microbiol Biotechnol Res 1(3):75–79

    Google Scholar 

  • Prentice H, Modi JP, Wu JY (2015) Mechanisms of neuronal protection against excitotoxicity, endoplasmic reticulum stress, and mitochondrial dysfunction in stroke and neurodegenerative diseases. Oxidative Med Cell Longev 2015:964518

    Google Scholar 

  • Pukumpuang W, Chansakaow S, Tragoolpua Y (2014) Antioxidant activity, phenolic compound content and phytochemical constituents of Eclipta prostrata (Linn.) Linn. Chiang Mai J Sci 41(3):568–576

    CAS  Google Scholar 

  • Ren ZL, Wang CD, Wang T, Ding H, Zhou M, Yang N, Liu YY, Chan P (2019) Ganoderma lucidum extract ameliorates MPTP-induced parkinsonism and protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis. Acta Pharmacol Sin 40(4):441–450

    CAS  Google Scholar 

  • Roy RK, Thakur M, Dixit VK (2008) Hair growth promoting activity of Eclipta alba in male albino rats. Arch Dermatol Res 300(7):357–364

    CAS  Google Scholar 

  • Sharma A, Kaur G (2018) Tinospora cordifolia as a potential neuroregenerative candidate against glutamate induced excitotoxicity: an in vitro perspective. BMC Complement Altern Med 18:268

    CAS  Google Scholar 

  • Sharma N, Kapoor M, Nehru B (2016) Apocyanin, NADPH oxidase inhibitor prevents lipopolysaccharide induced α-synuclein aggregation and ameliorates motor function deficits in rats: possible role of biochemical and inflammatory alterations. Behav Brain Res 296:177–190

    CAS  Google Scholar 

  • Sharma N, Nehru B (2015) Characterization of the lipopolysaccharide induced model of Parkinson’s disease: role of oxidative stress and neuroinflammation. Neurochem Int 87:92–105

    CAS  Google Scholar 

  • Sharma N, Sharma S, Nehru B (2017) Curcumin protects dopaminergic neurons against inflammation-mediated damage and improves motor dysfunction induced by single intranigral lipopolysaccharide injection. Inflammopharmacology 25(3):351–368

    CAS  Google Scholar 

  • Sim Y, Park G, Eo H, Huh E, Gu PS, Hong SP, Pak YK, Oh MS (2017) Protective effects of a herbal extract combination of Bupleurum falcatum, Paeonia suffruticosa, and Angelica dahurica against MPTP-induced neurotoxicity via regulation of nuclear receptor-related 1 protein. Neuroscience 340:166–175

    CAS  Google Scholar 

  • Trush MA, Mimnaugh EG, Ginsburg E, Gram TE (1981) In vitro stimulation by paraquat of reactive oxygen-mediated lipid peroxidation in rat lung microsomes. Toxicol Appl Pharmacol 60:279–286

    CAS  Google Scholar 

  • Wang H, Shao B, Yu H, Xu F, Wang P, Yu K, Han Y, Song M, Li Y, Cao Z (2019) Neuroprotective role of hyperforin on aluminum maltolate-induced oxidative damage and apoptosis in PC12 cells and SH-SY5Y cells. Chem Biol Interact 299:15–26

    CAS  Google Scholar 

  • Wang Q, Liu Y, Zhou J (2015) Neuroinflammation in Parkinson’s disease and its potential as therapeutic target. Transl Neurodegener 4:19

    Google Scholar 

  • Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L (2014) The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol 13(10):1045–1060

    CAS  Google Scholar 

  • Xie HR, Hu LS, Li GY (2010) SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson’s disease. Chin Med J 123(8):1086–1092

    CAS  Google Scholar 

  • Yang YL, Cheng X, Li WH, Liu M, Wang YH, Du GH (2019) Kaempferol attenuates LPS-induced striatum injury in mice involving anti-neuroinflammation, maintaining BBB integrity, and down-regulating the HMGB1/TLR4 pathway. Int J Mol Sci 20(3):491

    CAS  Google Scholar 

  • Zhao Y, Zhao B (2013) Oxidative stress and the pathogenesis of Alzheimer’s disease. Oxidative Med Cell Longev 2013:316523

    Google Scholar 

Download references

Funding

This work was supported by financial grant provided by Department of Science and Technology (DST-SERB), New Delhi, under the scheme of National Postdoctoral Fellowship wide order No. PDF/2016/002737.

Author information

Authors and Affiliations

Authors

Contributions

GB: formal analysis, investigation, methodology, data curation, and writing—original draft. JS: helped to analyze the in vitro study in the manuscript. BN: supervision and reviewing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Bimla Nehru.

Ethics declarations

Competing Interest

We wish to confirm that there are no known competing interests associated with this publication.

Ethical approval

The present study has been ethically approved by Institutional Animal Ethics Committee (Ethical approval number 109/IAEC/18).

Consent to participate

Not applicable. The present study does not involve any human participants, human data or human tissue.

Consent to publish

Not applicable. The present study does not contain any individual person’s data.

Additional information

Responsible Editor: Ludek Blaha

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bhatia, G., Singh, J. & Nehru, B. Neuroprotective effects of hydro-alcoholic extract of Eclipta alba against 1-methyl-4-phenylpyridinium-induced in vitro and in vivo models of Parkinson’s disease. Environ Sci Pollut Res 28, 9390–9406 (2021). https://doi.org/10.1007/s11356-020-11452-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-020-11452-1

Keywords

Navigation