Abstract
This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations’ effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10 mg/kg), group III (Cur EUD Nc 10 mg/kg), group IV (free Cur 10 mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30 min of treatment, the animals received the SCO and were subjected to behavioral tests 30 min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstrated that Cur treatment (Nc or free) protected against SCO-induced amnesia and depressive-like behavior. The ex vivo assays revealed lower acetylcholinesterase (AChE) and catalase (CAT) activity, reduced thiobarbituric species (TBARS), reactive species (RS), and non-protein thiols (NSPH) levels, and reduced interleukin-6 (IL-6) and tumor necrosis factor (TNF) expression. The treatments did not change hepatic markers in the plasma of mice. After treatments on alternate days, Cur Nc had a more significant effect than the free Cur protocol, implying that Cur may have prolonged action in Nc. This finding supports the concept that it is possible to achieve beneficial effects in nanoformulations, and treatment on alternate days differs from the free Cur protocol regarding anti-amnesic effects in mice.
Graphical abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
All data generated or analysed during this study are included in this published article [and its supplementary information files].
Code availability
Not applicable.
References
Aebi H (1984) [13] Catalase in vitro. pp 121–126
Akhtar A, Andleeb A, Waris TS et al (2021) Neurodegenerative diseases and effective drug delivery: a review of challenges and novel therapeutics. J Control Release 330:1152–1167. https://doi.org/10.1016/j.jconrel.2020.11.021
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4:807–818. https://doi.org/10.1021/mp700113r
Bagheri H, Ghasemi F, Barreto GE et al (2020) Effects of curcumin on mitochondria in neurodegenerative diseases. BioFactors 46:5–20. https://doi.org/10.1002/biof.1566
Balez R, Ooi L (2016) Getting to NO Alzheimer’s disease: neuroprotection versus neurotoxicity mediated by nitric oxide. Oxidative Med Cell Longev 2016:1–8. https://doi.org/10.1155/2016/3806157
Barbara R, Belletti D, Pederzoli F et al (2017) Novel curcumin loaded nanoparticles engineered for blood-brain barrier crossing and able to disrupt Abeta aggregates. Int J Pharm 526:413–424. https://doi.org/10.1016/j.ijpharm.2017.05.015
Battaglia S, Fabius JH, Moravkova K et al (2022) The neurobiological correlates of gaze perception in healthy individuals and neurologic patients. Biomedicines 10:627. https://doi.org/10.3390/biomedicines10030627
Boiangiu RS, Brinza I, Hancianu M et al (2020) Cognitive facilitation and antioxidant effects of an essential oil mix on scopolamine-induced amnesia in rats: molecular modeling of in vitro and in vivo approaches. Molecules 25:1519. https://doi.org/10.3390/molecules25071519
Borghans B (2015) Animal models for posttraumatic stress disorder: an overview of what is used in research. World J Psychiatry 5:387. https://doi.org/10.5498/wjp.v5.i4.387
Bostancıklıoğlu M (2019) An update on the interactions between Alzheimer’s disease, autophagy and inflammation. Gene 705:157–166. https://doi.org/10.1016/j.gene.2019.04.040
Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1006/abio.1976.9999
Cheon SY, Koo B-N, Kim SY et al (2021) Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice. Sci Rep 11:8376. https://doi.org/10.1038/s41598-021-87790-y
Chopra H, Dey PS, Das D et al (2021) Curcumin nanoparticles as promising therapeutic agents for drug targets. Molecules 26:4998. https://doi.org/10.3390/molecules26164998
Coradini K, Friedrich RB, Fonseca FN et al (2015) A novel approach to arthritis treatment based on resveratrol and curcumin co-encapsulated in lipid-core nanocapsules: in vivo studies. Eur J Pharm Sci 78:163–170. https://doi.org/10.1016/j.ejps.2015.07.012
da Costa Rodrigues K, Leivas de Oliveira R, da Silva CJ et al (2022) A new arylsulfanyl-benzo-2,1,3-thiadiazoles derivative produces an anti-amnesic effect in mice by modulating acetylcholinesterase activity. Chem Biol Interact 351:109736. https://doi.org/10.1016/j.cbi.2021.109736
Das S, Suresh PK, Desmukh R (2010) Design of Eudragit RL 100 nanoparticles by nanoprecipitation method for ocular drug delivery. Nanomedicine 6:318–323. https://doi.org/10.1016/j.nano.2009.09.002
dos Santos RB, Nakama KA, Pacheco CO et al (2021) Curcumin-loaded nanocapsules: influence of surface characteristics on technological parameters and potential antimalarial activity. Mater Sci Eng C 118:111356. https://doi.org/10.1016/j.msec.2020.111356
Dos Santos RB, Funguetto-Ribeiro AC, Maciel TR et al (2022) In vivo and in vitro per se effect evaluation of Polycaprolactone and Eudragit® RS100-based nanoparticles. Biomed Pharmacother 153:113410. https://doi.org/10.1016/j.biopha.2022.113410
Ege D (2021) Action mechanisms of curcumin in Alzheimer’s disease and its brain targeted delivery. Materials 14:3332. https://doi.org/10.3390/ma14123332
Eghbaliferiz S, Farhadi F, Barreto GE et al (2020) Effects of curcumin on neurological diseases: focus on astrocytes. Pharmacol Rep 72:769–782. https://doi.org/10.1007/s43440-020-00112-3
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77. https://doi.org/10.1016/0003-9861(59)90090-6
Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95. https://doi.org/10.1016/0006-2952(61)90145-9
Faul F, Erdfelder E, Lang A-G, Buchner A (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39:175–191. https://doi.org/10.3758/BF03193146
Francis PT, Palmer AM, Snape M, Wilcock GK (1999) The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J Neurol Neurosurg Psychiatry 66:137–147. https://doi.org/10.1136/jnnp.66.2.137
Garthwaite J (1991) Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 14:60–67. https://doi.org/10.1016/0166-2236(91)90022-M
Giacomeli R, Izoton JC, dos Santos RB et al (2019) Neuroprotective effects of curcumin lipid-core nanocapsules in a model Alzheimer’s disease induced by β-amyloid 1-42 peptide in aged female mice. Brain Res 1721:146325. https://doi.org/10.1016/j.brainres.2019.146325
Giacomeli R, de Gomes MG, Reolon JB et al (2020) Chrysin loaded lipid-core nanocapsules ameliorates neurobehavioral alterations induced by β-amyloid1-42 in aged female mice. Behav Brain Res 390:112696. https://doi.org/10.1016/j.bbr.2020.112696
Giongo JL, de Almeida VR, Sagrillo MR et al (2017) Anti-inflammatory effect of geranium nanoemulsion macrophages induced with soluble protein of Candida albicans. Microb Pathog 110:694–702. https://doi.org/10.1016/j.micpath.2017.01.056
Gomes GS, Maciel TR, Piegas EM et al (2018) Optimization of Curcuma oil/quinine-loaded Nanocapsules for malaria treatment. AAPS PharmSciTech 19:551–564. https://doi.org/10.1208/s12249-017-0854-6
Helli B, Gerami H, Kavianpour M et al (2021) Curcumin Nanomicelle improves lipid profile, stress oxidative factors and inflammatory markers in patients undergoing coronary elective angioplasty; a randomized clinical trial. Endocr Metab Immune Disord Drug Targets 21:2090–2098. https://doi.org/10.2174/1871530321666210104145231
Hoover DB (2017) Cholinergic modulation of the immune system presents new approaches for treating inflammation. Pharmacol Ther 179:1–16. https://doi.org/10.1016/j.pharmthera.2017.05.002
Hurley LL, Akinfiresoye L, Nwulia E et al (2013) Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF. Behav Brain Res 239:27–30. https://doi.org/10.1016/j.bbr.2012.10.049
Hussain H, Ahmad S, Shah SWA et al (2021) Neuroprotective potential of synthetic mono-carbonyl curcumin analogs assessed by molecular docking studies. Molecules 26:7168. https://doi.org/10.3390/molecules26237168
Hussain H, Ahmad S, Shah SWA et al (2022) Attenuation of scopolamine-induced amnesia via cholinergic modulation in mice by synthetic curcumin analogs. Molecules 27:2468. https://doi.org/10.3390/molecules27082468
Ighodaro OM, Akinloye OA (2018) First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): their fundamental role in the entire antioxidant defence grid. Alexandria Journal of Medicine 54:287–293. https://doi.org/10.1016/j.ajme.2017.09.001
Ismail Z, Elbayoumi H, Fischer CE et al (2017) Prevalence of depression in patients with mild cognitive impairment. JAMA Psychiatry 74:58. https://doi.org/10.1001/jamapsychiatry.2016.3162
Jäger E, Venturini CG, Poletto FS et al (2009) Sustained release from lipid-core Nanocapsules by varying the core viscosity and the particle surface area. J Biomed Nanotechnol 5:130–140. https://doi.org/10.1166/jbn.2009.1004
Jaguezeski AM, Gündel SS, Favarin FR et al (2019) Low-dose curcumin-loaded Eudragit L-100-nanocapsules in the diet of dairy sheep increases antioxidant levels and reduces lipid peroxidation in milk. J Food Biochem 43. https://doi.org/10.1111/jfbc.12942
Juszczyk G, Mikulska J, Kasperek K et al (2021) Chronic stress and oxidative stress as common factors of the pathogenesis of depression and Alzheimer’s disease: the role of antioxidants in prevention and treatment. Antioxidants 10:1439. https://doi.org/10.3390/antiox10091439
Kilimann I, Hausner L, Fellgiebel A et al (2016) Parallel atrophy of cortex and basal forebrain cholinergic system in mild cognitive impairment. Cerebral Cortex bhw019. https://doi.org/10.1093/cercor/bhw019
Loetchutinat C, Kothan S, Dechsupa S et al (2005) Spectrofluorometric determination of intracellular levels of reactive oxygen species in drug-sensitive and drug-resistant cancer cells using the 2′,7′-dichlorofluorescein diacetate assay. Radiat Phys Chem 72:323–331. https://doi.org/10.1016/j.radphyschem.2004.06.011
Manconi M, Manca ML, Escribano-Ferrer E et al (2019) Nanoformulation of curcumin-loaded eudragit-nutriosomes to counteract malaria infection by a dual strategy: improving antioxidant intestinal activity and systemic efficacy. Int J Pharm 556:82–88. https://doi.org/10.1016/j.ijpharm.2018.11.073
Mandal M, Jaiswal P, Mishra A (2020) Role of curcumin and its nanoformulations in neurotherapeutics: a comprehensive review. J Biochem Mol Toxicol 34. https://doi.org/10.1002/jbt.22478
Matias JN, Achete G, dos Santos Campanari GS et al (2021) A systematic review of the antidepressant effects of curcumin: beyond monoamines theory. Aust N Z J Psychiatr 55:451–462. https://doi.org/10.1177/0004867421998795
Naqvi F, Haider S, Naqvi F et al (2019) A comparative study showing greater effects of curcumin compared to donepezil on memory function in rats. Pak J Pharm Sci 32:53–60
Nuzzo D (2021) Role of natural antioxidants on neuroprotection and Neuroinflammation. Antioxidants 10:608. https://doi.org/10.3390/antiox10040608
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358. https://doi.org/10.1016/0003-2697(79)90738-3
Panzarini E, Mariano S, Tacconi S et al (2020) Novel therapeutic delivery of Nanocurcumin in central nervous system related disorders. Nanomaterials 11:2. https://doi.org/10.3390/nano11010002
Pignatello R, Ricupero N, Bucolo C et al (2006) Preparation and characterization of Eudragit retard nanosuspensions for the ocular delivery of cloricromene. AAPS PharmSciTech 7:E192–E198. https://doi.org/10.1208/pt070127
Pompl PN, Mullan MJ, Bjugstad K, Arendash GW (1999) Adaptation of the circular platform spatial memory task for mice: use in detecting cognitive impairment in the APPSW transgenic mouse model for Alzheimer’s disease. J Neurosci Methods 87:87–95. https://doi.org/10.1016/S0165-0270(98)00169-1
Ponchel G (1998) Specific and non-specific bioadhesive particulate systems for oral delivery to the gastrointestinal tract. Adv Drug Deliv Rev 34:191–219. https://doi.org/10.1016/S0169-409X(98)00040-4
Rahimzadegan M, Soodi M (2018) Comparison of memory impairment and oxidative stress following single or repeated doses Administration of Scopolamine in rat Hippocampus. Basic Clin Neurosci J 9:5–14. https://doi.org/10.29252/nirp.bcn.9.1.5
Razavi BM, Hosseinzadeh H (2020) Antioxidant effects of Curcuma longa and its active constituent, curcumin, for the therapy of neurological disorders. In: Oxidative Stress and Dietary Antioxidants in Neurological Diseases. Elsevier, pp 249–269
Reddy PH, Manczak M, Yin X et al (2018) Protective effects of Indian spice curcumin against amyloid-β in Alzheimer’s disease. J Alzheimers Dis 61:843–866. https://doi.org/10.3233/JAD-170512
Sakaguchi M, Koseki M, Wakamatsu M, Matsumura E (2006) Effects of systemic administration of β-casomorphin-5 on learning and memory in mice. Eur J Pharmacol 530:81–87. https://doi.org/10.1016/j.ejphar.2005.11.014
Sarandol A, Sarandol E, Eker SS, Erdinc S, Vatansever E, Kirli S (2007) Major depressive disorder isaccompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative-antioxidative systems. Hum Psychopharmacol 22(2):67–73. https://doi.org/10.1002/hup.829
Sarter M, Bodewitz G, Stephens DN (1988) Attenuation of scopolamine-induced impairment of spontaneous alternation behaviour by antagonist but not inverse agonist and agonist ?-carbolines. Psychopharmacology 94:491–495. https://doi.org/10.1007/BF00212843
Seo H-J, Wang S-M, Han C et al (2015) Curcumin as a putative antidepressant. Expert Rev Neurother 15:269–280. https://doi.org/10.1586/14737175.2015.1008457
Soliman GM, Redon R, Sharma A et al (2014) Miktoarm star polymer based multifunctional traceable Nanocarriers for efficient delivery of poorly water soluble pharmacological agents. Macromol Biosci 14:1312–1324. https://doi.org/10.1002/mabi.201400123
Soltani S, Zakeri-Milani P, Barzegar-Jalali M, Jelvehgari M (2016) Design of eudragit RL nanoparticles by nanoemulsion method as carriers for ophthalmic drug delivery of ketotifen fumarate. Iran J Basic Med Sci 19:550–560
SoukhakLari R, Moezi L, Pirsalami F et al (2018) Curcumin ameliorates scopolamine-induced mice memory retrieval deficit and restores hippocampal p-Akt and p-GSK-3β. Eur J Pharmacol 841:28–32. https://doi.org/10.1016/j.ejphar.2018.10.012
Souza MA, Magni DV, Guerra GP et al (2012) Involvement of hippocampal CAMKII/CREB signaling in the spatial memory retention induced by creatine. Amino Acids 43:2491–2503. https://doi.org/10.1007/s00726-012-1329-4
Stanciu GD, Luca A, Rusu RN et al (2019) Alzheimer’s disease pharmacotherapy in relation to cholinergic system involvement. Biomolecules 10:40. https://doi.org/10.3390/biom10010040
Stangherlin EC, Rocha JBT, Nogueira CW (2009) Diphenyl ditelluride impairs short-term memory and alters neurochemical parameters in young rats. Pharmacol Biochem Behav 91:430–435. https://doi.org/10.1016/j.pbb.2008.08.020
Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370. https://doi.org/10.1007/BF00428203
Tang M, Taghibiglou C (2017) The mechanisms of action of curcumin in Alzheimer’s disease. J Alzheimers Dis 58:1003–1016. https://doi.org/10.3233/JAD-170188
Teixeira MI, Lopes CM, Amaral MH, Costa PC (2020) Current insights on lipid nanocarrier-assisted drug delivery in the treatment of neurodegenerative diseases. Eur J Pharm Biopharm 149:192–217. https://doi.org/10.1016/j.ejpb.2020.01.005
Umerska A, Gaucher C, Oyarzun-Ampuero F et al (2018) Polymeric nanoparticles for increasing oral bioavailability of curcumin. Antioxidants 7:46. https://doi.org/10.3390/antiox7040046
Vieira SM, Michels LR, Roversi K et al (2016) A surface modification of clozapine-loaded nanocapsules improves their efficacy: a study of formulation development and biological assessment. Colloids Surf B Biointerfaces 145:748–756. https://doi.org/10.1016/j.colsurfb.2016.05.065
Villemagne VL, Burnham S, Bourgeat P et al (2013) Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 12:357–367. https://doi.org/10.1016/S1474-4422(13)70044-9
Walsh RN, Cummins RA (1976) The open-field test: a critical review. Psychol Bull 83:482–504. https://doi.org/10.1037/0033-2909.83.3.482
Wang M, Jiang S, Zhou L et al (2019) Potential mechanisms of action of curcumin for Cancer prevention: focus on cellular signaling pathways and miRNAs. Int J Biol Sci 15:1200–1214. https://doi.org/10.7150/ijbs.33710
Weiss C, Carriere M, Fusco L et al (2020) Toward nanotechnology-enabled approaches against the COVID-19 pandemic. ACS Nano 14:6383–6406. https://doi.org/10.1021/acsnano.0c03697
Wu D, Xu X, Sun N et al (2020) AGLPM and QMDDQ peptides exert a synergistic action on memory improvement against scopolamine-induced amnesiac mice. Food Funct 11:10925–10935. https://doi.org/10.1039/D0FO02570D
Yanagisawa D, Amatsubo T, Morikawa S et al (2011) In vivo detection of amyloid β deposition using 19F magnetic resonance imaging with a 19F-containing curcumin derivative in a mouse model of Alzheimer’s disease. Neuroscience 184:120–127. https://doi.org/10.1016/j.neuroscience.2011.03.071
Yavarpour-Bali H, Ghasemi-Kasman M, Pirzadeh M (2019) Curcumin-loaded nanoparticles: a novel therapeutic strategy in treatment of central nervous system disorders. Int J Nanomedicine 14:4449–4460. https://doi.org/10.2147/IJN.S208332
Zeng M, Xu J, Luo Q et al (2020) Constructing antibacterial polymer nanocapsules based on pyridine quaternary ammonium salt. Mater Sci Eng C 108:110383. https://doi.org/10.1016/j.msec.2019.110383
Acknowledgments
We are grateful for the financial support and scholarships from the Brazilian agencies CNPq (UNIVERSAL 429859/2018-0), FAPERGS (PqG 17/2551-0001013-2 and 19/2551-0001745-6). CNPq is also acknowledged for the fellowship to KCR (160674/2020-4), CL, EAW, LS, and NLCD. This study was funded in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) - Finance Code 001. We would also like to thank Atlas Assessoria Linguística for language editing.
Funding
Financial support and scholarships from the Brazilian agencies CNPq (UNIVERSAL 429859/2018–0), FAPERGS (PqG 17/2551–0001013-2 and 19/2551–0001745-6). CNPq is also acknowledged for the fellowship to KCR (160674/2020–4), CL, EAW, LS, and NLCD. This study was funded in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) - Finance Code 001. We would also like to thank Atlas Assessoria Linguística for language editing.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. Rodrigues KC: conceptualization, methodology, formal analysis, investigation, writing—original draft. Luchese C and Whilhelm EA: conceptualization, verification, resources, writing—review and editing, supervision, project administration, funding acquisition. Neto MRS; Hass S; Barboza VS; Schumacher RS; Giongo JL and Voucher RA: methodology, formal analysis.
Corresponding author
Ethics declarations
Ethics approval
All procedures were approved by the Committee on Care and Use of Experimental Animal Resources of the Federal University of Pelotas, Brazil (CEEA number 038773/2021–50) and in accordance with the guide of the Brazilian National Animal Care Ethical Council (CONCEA), which is based on National Institutes of Health Guidelines for the Care and Use of Laboratory Animals (Publication no. 85–23, revised 1985).
Consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors have non-financial interests to disclose.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
ESM 1
(PDF 676 kb)
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
da Costa Rodrigues, K., da Silva Neto, M.R., dos Santos Barboza, V. et al. New curcumin-loaded nanocapsules as a therapeutic alternative in an amnesia model. Metab Brain Dis 39, 589–609 (2024). https://doi.org/10.1007/s11011-023-01329-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-023-01329-w