Parkinson’s disease is a progressive and irreversible neurodegenerative disease, whose main characteristic is the death of dopaminergic neurons. The animal model of Parkinsonism with reserpine has been used to mimic the consequences of Parkinson’s disease. The use of gold nanoparticles in the treatment of several diseases arises due to their evidence of promising antioxidant and anti-inflammatory properties. Curcumin, in turn, presents neuroprotective activity in neurodegenerative diseases by reducing both inflammatory activity and oxidative stress in models of Parkinson’s disease. This article seeks to understand the effects of the use of gold nanoparticles biosynthesized with curcumin in an experimental model of Parkinson’s disease with reserpine. C57BL/6 mice were used, divided into five groups: I. Control; II. Parkinson’s disease; III. Parkinson’s disease + Gold nanoparticles; IV. Parkinson’s disease + Curcumin; V. Parkinson’s disease + Gold nanoparticles biosynthesized with curcumin. Mice were subjected to subcutaneous induction with reserpine, and treatments began 24 h after administration. Seven treatments were applied at 24-h intervals via the intranasal route. After the last treatment, behavioral tests were conducted, followed by euthanasia and removal of brain structures. The combined treatments demonstrated potential neuroprotective effects, reversing inflammatory and oxidative processes and partially reversing Parkinsonian behavior. Together, these therapies potentiated their effects, leading to near-complete reversal of reserpine-induced damage.
de LauLMBretelerMM. Epidemiology of Parkinson’s disease. Lancet Neurol2006; 5(6): 525–535.
2.
NussbaumRLEllisCE. Alzheimer’s disease and Parkinson’s disease. N Engl J Med2003; 348(14): 1356–1364.
3.
TanseyMGWallingsRLHouserMC, et al.Inflammation and immune dysfunction in parkinson disease. Nat Rev Immunol2022; 22(11): 657–673.
4.
ZamanianMYNazifiMKhachatryanLG, et al.The neuroprotective effects of agmatine on Parkinson’s disease: focus on oxidative stress, inflammation and molecular mechanisms. Inflammation2025; 48(3): 1078–1092.
5.
SilveiraPCVenâncioMSouzaPS, et al.Iontophoresis with gold nanoparticles improves mitochondrial activity and oxidative stress markers of burn wounds. Mater Sci Eng C2014; 44: 380–385.
6.
YangYHuYDuH, et al.Colloidal plasmonic gold nanoparticles and gold nanorings: shape-dependent generation of singlet oxygen and their performance in enhanced photodynamic cancer therapy. Int J Nanomed2018; 13: 2065–2078.
7.
ElbialyNSAbdelfatahEAKhalilWA. Antitumor activity of curcumin-green synthesized gold nanoparticles: in vitro study. BioNanoScience2019; 9(4): 813–820.
8.
BrunieraJFBGabriel-SilvaLGoulartRS, et al.Green synthesis, characterization and antimicrobial evaluation of silver nanoparticles for an intracanal dressing. Braz Dent J2020; 31(5): 485–492.
9.
SilveiraGBMullerAPMachado-de-ÁvilaRA, et al.Advance in the use of gold nanoparticles in the treatment of neurodegenerative diseases: new perspectives. Neural Regen Res2021; 16(12): 2425–2426.
10.
WangJSuiMFanW. Nanoparticles for tumor targeted therapies and their pharmacokinetics. Curr Drug Metabol2010; 11(2): 129–141.
11.
JinTZhangYBotchwayBOA, et al.Curcumin can improve Parkinson’s disease via activating BDNF/PI3k/Akt signaling pathways. Food Chem Toxicol2022; 164: 113091.
12.
VianaGSValeTGPinhoRS, et al.Antinociceptive effect of the essential oil from Cymbopogon citratus in mice. J Ethnopharmacol2000; 70(3): 323–327.
13.
da Silva CórneoEde Bem SilveiraGScusselR, et al.Effects of gold nanoparticles administration through behavioral and oxidative parameters in animal model of Parkinson’s disease. Colloids Surf B Biointerfaces2020; 196: 111302.
14.
RafieezadehDSabetiGKhalajiA, et al.Advances in nanotechnology for targeted drug delivery in neurodegenerative diseases. Am J Neurodegener Dis2025; 14(2): 51–57.
15.
LowryOHRosebroughNJFarrAL, et al.Protein measurement with the folin phenol reagent. J Biol Chem1951; 193(1): 265–275.
16.
WangHJosephJA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med1999; 27(5-6): 612–616.
17.
ChaeSYLeeMKimSW, et al.Protection of insulin secreting cells from nitric oxide induced cellular damage by crosslinked hemoglobin. Biomaterials2004; 25(5): 843–850.
18.
BannisterJVCalabreseL. Assays for superoxide dismutase. Methods Biochem Anal1987; 32: 279–312.
19.
HissinPJHilfR. A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem1976; 74(1): 214–226.
20.
ThirupathiAGuzzattiMFMCorrêaM, et al.Green synthesis of gold nanoparticles with curcumin or Açai in the tissue repair of palatal wounds. Antioxidants2023; 12(8): 1574.
21.
KalantariHTurnerRJ. Structural and antimicrobial properties of synthesized gold nanoparticles using biological and chemical approaches. Front Chem2024; 12: 1482102.
22.
TeixeiraBHGonçalvesKOVieiraDP, et al.Synergizing immune balance: Curcumin gold nanoparticles and ultrasound irradiation for macrophage down-regulation. AppliedChem2024; 4(1): 70–85.
23.
MullerAPFerreiraGKda SilvaS, et al.Safety protocol for the gold nanoparticles administration in rats. Mater Sci Eng C2017; 77: 1145–1150.
24.
GaoGZhangMGongD, et al.The size-effect of gold nanoparticles and nanoclusters in the inhibition of amyloid-β fibrillation. Nanoscale2017; 9(12): 4107–4113.
25.
BilalMBaraniMSabirF, et al.Nanomaterials for the treatment and diagnosis of Alzheimer’s disease: an overview. NanoImpact2020; 20: 100251.
26.
GrancharovaTSimeonovaSPilichevaB, et al.Gold nanoparticles in Parkinson’s disease therapy: a focus on plant-based green synthesis. Cureus2024; 16(2): e54671.
27.
KhatriDKPreetiKTonapeS, et al.Nanotechnological advances for nose to brain delivery of therapeutics to improve the Parkinson therapy. Curr Neuropharmacol2023; 21(3): 493–516.
28.
ChenYZhangCHuangY, et al.Intranasal drug delivery: the interaction between nanoparticles and the nose-to-brain pathway. Adv Drug Deliv Rev2024; 207: 115196.
29.
AgrawalMSarafSSarafS, et al.Nose-to-brain drug delivery: an update on clinical challenges and progress towards approval of anti-Alzheimer drugs. J Contr Release2018; 281: 139–177.
30.
KayeADSalaKRDethloffD, et al.The evolving use of gold nanoparticles as a possible reversal agent for the symptoms of neurodegenerative diseases: a narrative review. Cureus2024; 16(7): e64846.
31.
GerlachMRiedererP. Animal models of Parkinson’s disease: an empirical comparison with the phenomenology of the disease in man. J Neural Transm1996; 103(8-9): 987–1041.
32.
AbílioVCAraujoCCBergamoM, et al.Vitamin E attenuates reserpine-induced oral dyskinesia and striatal oxidized glutathione/reduced glutathione ratio (GSSG/GSH) enhancement in rats. Prog Neuropsychopharmacol Biol Psychiatry2003; 27(1): 109–114.
33.
SteinpreisRESalamoneJD. Effects of acute haloperidol and reserpine administration on vacuous jaw movements in three different age groups of rats. Pharmacol Biochem Behav1993; 46(2): 405–409.
34.
SalamoneJBaskinP. Vacuous jaw movements induced by acute reserpine and low-dose apomorphine: possible model of Parkinsonian tremor. Pharmacol Biochem Behav1996; 53(1): 179–183.
35.
ColpaertFC. Pharmacological characteristics of tremor, rigidity and hypokinesia induced by reserpine in rat. Neuropharmacology1987; 26(9): 1431–1440.
36.
LeãoAHSarmento-SilvaAJSantosJR, et al.Molecular, neurochemical, and behavioral hallmarks of reserpine as a model for Parkinson’s disease: new perspectives to a long-standing model. Brain Pathol2015; 25(4): 377–390.
37.
BishnoiMChopraKKulkarniSK. Protective effect of curcumin, the active principle of turmeric (Curcuma longa) in haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes in rat brain. Pharmacol Biochem Behav2008; 88(4): 511–522.
38.
MansouriZSabetkasaeiMMoradiF, et al.Curcumin has neuroprotection effect on homocysteine rat model of Parkinson. J Mol Neurosci2012; 47(2): 234–242.
39.
CuiQLiXZhuH. Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway. Mol Med Rep2016; 13(2): 1381–1388.
40.
KoWCWangSJHsiaoCY, et al.Pharmacological role of functionalized gold nanoparticles in disease applications. Molecules2022; 27(5): 1551.
41.
PatelTAKevadiyaBDBajwaN, et al.Role of nanoparticle-conjugates and nanotheranostics in abrogating oxidative stress and ameliorating neuroinflammation. Antioxidants2023; 12(10): 1877.
42.
ChiangMCYangYPNicolCJB, et al.Gold nanoparticles in neurological diseases: a review of neuroprotection. Int J Mol Sci2024; 25(4): 2360.
43.
SanbergPRBunseyMDGiordanoM, et al.The catalepsy test: its ups and downs. Behav Neurosci1988; 102(5): 748–759.
44.
BurgerMEAlvesACallegariL, et al.Ebselen attenuates reserpine-induced orofacial dyskinesia and oxidative stress in rat striatum. Prog Neuropsychopharmacol Biol Psychiatry2003; 27(1): 135–140.
45.
AroraBHoCLHoyerJD, et al.Bone marrow angiogenesis and its clinical correlates in myelofibrosis with myeloid metaplasia. Haematologica2004; 89(12): 1454–1458.
46.
LealPCLinsLCde GoisAM, et al.Commentary: evaluation of models of Parkinson’s disease. Front Neurosci2016; 10: 283.
47.
Dos Santos TramontinNda SilvaSArrudaR, et al.Gold nanoparticles treatment reverses brain damage in Alzheimer’s disease model. Mol Neurobiol2020; 57(2): 926–936.
48.
AbercrombieEDDeBoerPHeeringaMJ. Biochemistry of somatodendritic dopamine release in substantia nigra: an in vivo comparison with striatal dopamine release. Adv Pharmacol1998; 42: 133–136.
49.
HornykiewiczO. The discovery of dopamine deficiency in the Parkinsonian brain. J Neural Transm Suppl2006; 70: 9–15.
50.
HuangRWangXZhouY, et al.RANKL-induced M1 macrophages are involved in bone formation. Bone Res2017; 5: 17019.
51.
SzelÉNyiJKissJPPuskÁSÉ, et al.Contribution of differently localized α2-and β-Adrenoceptors in the modulation of TNF-α and IL-10 production in endotoxemic mice. Ann N Y Acad Sci2000; 917(1): 145–153.
52.
SeadyMSchirmbeckGTadayJ, et al.Curcumin attenuates neuroinflammatory damage induced by LPS: implications for the role of S100B. J Nutr Biochem2025; 135: 109768.
53.
BuhrmannCMobasheriABuschF, et al.Curcumin modulates nuclear factor kappaB (NF-kappaB)-mediated inflammation in human tenocytes in vitro: role of the phosphatidylinositol 3-kinase/Akt pathway. J Biol Chem2011; 286(32): 28556–28566.
54.
HuangCBaoQHuntingD, et al.Conformation-dependent DNA damage induced by gold nanoparticles. J Biomed Nanotechnol2013; 9(5): 856–862.
55.
ParadaEBuendiaINavarroE, et al.Microglial HO-1 induction by curcumin provides antioxidant, antineuroinflammatory, and glioprotective effects. Mol Nutr Food Res2015; 59(9): 1690–1700.
56.
ZhuYGChenXCChenZZ, et al.Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons. Acta Pharmacol Sin2004; 25(12): 1606–1612.
57.
SoodPKNaharUNehruB. Curcumin attenuates aluminum-induced oxidative stress and mitochondrial dysfunction in rat brain. Neurotox Res2011; 20(4): 351–361.
58.
JeonKIByunMSJueDM. Gold compound auranofin inhibits IkappaB kinase (IKK) by modifying Cys-179 of IKKbeta subunit. Exp Mol Med2003; 35(2): 61–66.
59.
NaiduPSSinghAKulkarniSK. Effect of Withania somnifera root extract on reserpine-induced orofacial dyskinesia and cognitive dysfunction. Phytother Res2006; 20(2): 140–146.
60.
TeixeiraAMTrevizolFColpoG, et al.Influence of chronic exercise on reserpine-induced oxidative stress in rats: behavioral and antioxidant evaluations. Pharmacol Biochem Behav2008; 88(4): 465–472.
61.
WangSDuanMGuanK, et al.Developmental neurotoxicity of reserpine exposure in zebrafish larvae (Danio rerio). Comp Biochem Physiol C Toxicol Pharmacol2019; 223: 115–123.
62.
OrtizGGPacheco MoisésFPMireles-RamírezM, et al.Oxidative stress: love and hate history in central nervous system. Adv Protein Chem Struct Biol2017; 108: 1–31.
63.
PatelAOlangCALewisG, et al.An overview of Parkinson’s disease: Curcumin as a possible alternative treatment. Cureus2022; 14(5): e25032.
64.
HuangTZhaoJGuoD, et al.Curcumin mitigates axonal injury and neuronal cell apoptosis through the PERK/Nrf2 signaling pathway following diffuse axonal injury. Neuroreport2018; 29(8): 661–677.
65.
SarkarBDhimanMMittalS, et al.Curcumin revitalizes Amyloid beta (25-35)-induced and organophosphate pesticides pestered neurotoxicity in SH-SY5Y and IMR-32 cells via activation of APE1 and Nrf2. Metab Brain Dis2017; 32(6): 2045–2061.
66.
LiWSuwanwelaNCPatumrajS. Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R. Microvasc Res2016; 106: 117–127.
67.
XieYZhaoQYLiHY, et al.Curcumin ameliorates cognitive deficits heavy ion irradiation-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways. Pharmacol Biochem Behav2014; 126: 181–186.
68.
KajitaEOkanoJTBodineEN, et al.Modelling an outbreak of an emerging pathogen. Nat Rev Microbiol2007; 5(9): 700–709.
69.
AshrafizadehMAhmadiZMohammadinejadR, et al.Curcumin activates the Nrf2 pathway and induces cellular protection against oxidative injury. Curr Mol Med2020; 20(2): 116–133.
MaJSKimWJKimJJ, et al.Gold nanoparticles attenuate LPS-induced NO production through the inhibition of NF-kappaB and IFN-beta/STAT1 pathways in RAW264.7 cells. Nitric Oxide2010; 23(3): 214–219.
72.
LalRSinghAWattsSChopraK. Experimental models of Parkinson's disease: Challenges and Opportunities. Eur J Pharmacol. 2024 Oct 5;980:176819. doi: 10.1016/j.ejphar.2024.176819. Epub 2024 Jul 18.
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