Naringenin Nanocrystals Mitigate Rotenone Neurotoxicity in SH-SY5Y Cell Line by Modulating Mitophagy and Oxidative Stress.
Humans
Flavanones
/ pharmacology
Nanoparticles
/ chemistry
Oxidative Stress
/ drug effects
Rotenone
/ toxicity
Cell Line, Tumor
Reactive Oxygen Species
/ metabolism
Membrane Potential, Mitochondrial
/ drug effects
Mitophagy
/ drug effects
Antioxidants
/ pharmacology
Cell Survival
/ drug effects
Particle Size
Mitochondria
/ drug effects
Solubility
Neuroprotective Agents
/ pharmacology
Mitochondrial oxidative stress
nanocrystals
neuroprotective
reactive oxygen species
rotenone neurotoxicity
Journal
AAPS PharmSciTech
ISSN: 1530-9932
Titre abrégé: AAPS PharmSciTech
Pays: United States
ID NLM: 100960111
Informations de publication
Date de publication:
30 Sep 2024
30 Sep 2024
Historique:
received:
24
07
2024
accepted:
06
09
2024
medline:
1
10
2024
pubmed:
1
10
2024
entrez:
30
9
2024
Statut:
epublish
Résumé
Naringenin, a potent antioxidant with anti-apoptotic effects, holds potential in counteracting rotenone-induced neurotoxicity, a model for Parkinson's disease, by reducing oxidative stress and supporting mitochondrial function. Rotenone disrupts ATP production in SH-SY5Y cells through mitochondrial complex-I inhibition, leading to increased reactive oxygen species (ROS) and cellular damage. However, the therapeutic use of naringenin is limited by its poor solubility, low bioavailability, and stability concerns. Nano crystallization of naringenin (NCs), significantly improved its solubility, dissolution rates, and stability for targeted drug delivery. The developed NAR-NC and HSA-NAR-NC formulations exhibit particle sizes of 95.23 nm and 147.89 nm, with zeta potentials of -20.6 mV and -28.5 mV, respectively. These nanocrystals also maintain high drug content and show stability over time, confirming their pharmaceutical viability. In studies using the SH-SY5Y cell line, these modified nanocrystals effectively preserved mitochondrial membrane potential, sustained ATP production, and regulated ROS levels, counteracting the neurotoxic effects of rotenone. Naringenin nanocrystals offer a promising solution for improving the stability and bioavailability of naringenin, with potential therapeutic applications in neurodegenerative diseases.
Identifiants
pubmed: 39349907
doi: 10.1208/s12249-024-02936-1
pii: 10.1208/s12249-024-02936-1
doi:
Substances chimiques
Flavanones
0
naringenin
HN5425SBF2
Rotenone
03L9OT429T
Reactive Oxygen Species
0
Antioxidants
0
Neuroprotective Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
227Informations de copyright
© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.
Références
Stefanis L. α-Synuclein in Parkinson’s Disease. Cold Spring Harb Perspect Med . 2012;2. https://doi.org/10.1101/cshperspect.a009399 .
Bjorklund G, Stejskal V, Urbina MA, Dadar M, Chirumbolo S, Mutter J. Metals and Parkinson’s Disease: Mechanisms and Biochemical Processes. Curr Med Chem. 2018;25:2198–214.
doi: 10.2174/0929867325666171129124616
pubmed: 29189118
Zou L, Che Z, Ding K, Zhang C, Liu X, Wang L, et al. JAC4 Alleviates Rotenone-Induced Parkinson’s Disease through the Inactivation of the NLRP3 Signal Pathway. Antioxidants [Internet]. 2023;12. https://doi.org/10.3390/antiox12051134 .
McGregor MM, Nelson AB. Circuit Mechanisms of Parkinson’s Disease. Neuron. 2019;101:1042–56.
doi: 10.1016/j.neuron.2019.03.004
pubmed: 30897356
Emran T Bin, Islam F, Nath N, Sutradhar H, Das R, Mitra S, et al. Naringin and Naringenin Polyphenols in Neurological Diseases: Understandings from a Therapeutic Viewpoint. Life [Internet]. 2023;13. https://doi.org/10.3390/life13010099 .
Steiner JA, Quansah E, Brundin P. The concept of alpha-synuclein as a prion-like protein: ten years after. Cell Tissue Res. 2018;373:161–73.
doi: 10.1007/s00441-018-2814-1
pubmed: 29480459
pmcid: 6541204
Katiyar N, Singhaƒ MN, Yadav P, Narayan Singh H, Saha S, Saraf SA. Development of Naringenin Nanocrystals for Enhanced Solubility and Bioavailability. Am J PharmTech Res. 2018;8:110–28.
Jankovic J, Tan EK. Parkinson’s disease: Etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry. 2020;91:795–808.
doi: 10.1136/jnnp-2019-322338
pubmed: 32576618
Ravetti S, Garro AG, Gaitán A, Murature M, Galiano M, Brignone SG, et al. Naringin: Nanotechnological Strategies for Potential Pharmaceutical Applications. Pharmaceutics [Internet]. 2023;15. https://doi.org/10.3390/pharmaceutics15030863 .
Bhia M, Motallebi M, Abadi B, Zarepour A, Pereira-Silva M, Saremnejad F, et al. Naringenin nano-delivery systems and their therapeutic applications. mdpi.com [Internet]. 2021 [cited 2022 Sep 29];13:291. Available from: https://www.mdpi.com/1009088 .
Mule S, Khairnar P, Shukla R. Recent Advances in Nanocrystals Heralding Greater Potential in Brain Delivery. Particle & Particle Systems Characterization [Internet]. 2022 [cited 2022 Oct 27];39:2200087. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/ppsc.202200087 .
Jha DK, Shah DS, Talele SR, Amin PD. Correlation of two validated methods for the quantification of naringenin in its solid dispersion: HPLC and UV spectrophotometric methods. SN Appl Sci. 2020;2.
Gera S, Talluri S, Rangaraj N, Sampathi S. Formulation and Evaluation of Naringenin Nanosuspensions for Bioavailability Enhancement. AAPS PharmSciTech. 2017;18:3151–62.
doi: 10.1208/s12249-017-0790-5
pubmed: 28534300
S.E Eltayeb. Preparation and optimization of transferrin-modified-artemether lipid nanospheres based on the orthogonal design of emulsion formulation and physically electrostatic adsorption.
Camacho Vieira C, Peltonen L, Karttunen AP, Ribeiro AJ. Is it advantageous to use quality by design (QbD) to develop nanoparticle-based dosage forms for parenteral drug administration? Int J Pharm. 2024;657.
Grangeia HB, Silva C, Simões SP, Reis MS. Quality by design in pharmaceutical manufacturing: A systematic review of current status, challenges and future perspectives. Eur J Pharm Biopharm. 2020;147:19–37.
doi: 10.1016/j.ejpb.2019.12.007
pubmed: 31862299
Pramod K, Tahir MA, Charoo NA, Ansari SH, Ali J. Pharmaceutical product development: A quality by design approach. Int J Pharm Investig [Internet]. 2016;6:129. https://doi.org/10.4103/2230-973X.187350 .
Singh B. Quality by Design (QbD) for Holistic Pharma Excellence and Regulatory Compliance [Internet]. Pharma Times. 2014. Available from: https://www.researchgate.net/publication/267034196 . Accessed Mar 2022
Fukuda IM, Pinto CFF, Moreira CDS, Saviano AM, Lourenço FR. Design of experiments (DoE) applied to pharmaceutical and analytical quality by design (QbD). Brazilian Journal of Pharmaceutical Sciences. Faculdade de Ciencias Farmaceuticas (Biblioteca); 2018.
Cheng M, Yuan F, Liu J, Liu W, Feng J, Jin Y, et al. Fabrication of Fine Puerarin Nanocrystals by Box–Behnken Design to Enhance Intestinal Absorption. AAPS PharmSciTech 2020 21:3 [Internet]. 2020 [cited 2022 Sep 29];21:1–12. Available from: https://link.springer.com/article/10.1208/s12249-019-1616-4 .
Pardhi VP, Verma T, Flora SJS, Chandasana H, Shukla R. Nanocrystals: An Overview of Fabrication, Characterization and Therapeutic Applications in Drug Delivery. Curr Pharm Des. 2019;24:5129–46.
doi: 10.2174/1381612825666190215121148
Akhter MH, Kumar S, Nomani S. Sonication tailored enhance cytotoxicity of naringenin nanoparticle in pancreatic cancer: design, optimization, and in vitro studies. Drug Dev Ind Pharm. 2020;46:659–72.
doi: 10.1080/03639045.2020.1747485
pubmed: 32208984
Shegokar R, Müller RH. Nanocrystals: Industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm. 2010;129–39.
Wu C, Li B, Zhang Y, Chen T, Chen C, Jiang W, et al. Intranasal delivery of paeoniflorin nanocrystals for brain targeting. Asian J Pharm Sci. 2020;15:326–35.
doi: 10.1016/j.ajps.2019.11.002
pubmed: 32636950
Kumar SP, Birundha K, Kaveri K, Devi KTR. Antioxidant studies of chitosan nanoparticles containing naringenin and their cytotoxicity effects in lung cancer cells. Int J Biol Macromol. 2015;78:87–95.
doi: 10.1016/j.ijbiomac.2015.03.045
pubmed: 25840152
Juan-García A, Tolosa J, Juan C, Ruiz MJ. Cytotoxicity, genotoxicity and disturbance of cell cycle in hepg2 cells exposed to OTA and BEA: Single and combined actions. Toxins (Basel). 2019;11.
Lawana V, Um SY, Rochet JC, Turesky RJ, Shannahan JH, Cannon JR. Neuromelanin Modulates Heterocyclic Aromatic Amine-Induced Dopaminergic Neurotoxicity. Toxicol Sci. 2020;173:171–88.
doi: 10.1093/toxsci/kfz210
pubmed: 31562763
Agahi F, Juan-García A, Font G, Juan C. Study of enzymatic activity in human neuroblastoma cells SH-SY5Y exposed to zearalenone’s derivates and beauvericin. Food Chem Toxicol. 2021;152: 112227.
doi: 10.1016/j.fct.2021.112227
pubmed: 33878370
Xia D, Quan P, Piao H, Piao H, Sun S, Yin Y, et al. Preparation of stable nitrendipine nanosuspensions using the precipitation-ultrasonication method for enhancement of dissolution and oral bioavailability. Eur J Pharm Sci. 2010;40:325–34.
doi: 10.1016/j.ejps.2010.04.006
pubmed: 20417274
Mhaske A, Kaur J, Naqvi S, Shukla R. Decitabine enclosed biotin-zein conjugated nanoparticles: synthesis, characterization, in vitro and in vivo evaluation. Nanomedicine. 2024.
Zeeshan M, Murugadas A, Ghaskadbi S, Rajendran RB, Akbarsha MA. ROS dependent copper toxicity in Hydra-biochemical and molecular study. Comp Biochem Physiol C: Toxicol Pharmacol. 2016;185–186:1–12.
pubmed: 26945520
Zhao G, Yao-Yue C, Qin GW, Guo LH. Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons. Neurobiol Aging. 2012;33:176–86.
doi: 10.1016/j.neurobiolaging.2010.02.013
pubmed: 20382451
Cao Y, Wu T, Dai W, Dong H, Zhang X. TiO2 Nanosheets with the Au Nanocrystal-Decorated Edge for Mitochondria-Targeting Enhanced Sonodynamic Therapy. Chemistry of Materials [Internet]. 2019 [cited 2022 Mar 30]; Available from: https://pubs.acs.org/doi/abs/10.1021/acs.chemmater.9b03430 .
Ex Vivo Programming of Dendritic Cell by Mitochondria-Targeted Nanoparticles to Produce Interferon-Gamma for Cancer Immunotherapy. 2013.
Zhang Y, Guo H, Guo X, Ge D, Shi Y, Lu X, et al. Involvement of Akt/mTOR in the Neurotoxicity of Rotenone-Induced Parkinson’s Disease Models. International Journal of Environmental Research and Public Health 2019, Vol 16, Page 3811 [Internet]. 2019 [cited 2024 Jun 29];16:3811. Available from: https://www.mdpi.com/1660-4601/16/20/3811/htm .
Han X, Han B, Zhao Y, Li G, Wang T, He J, et al. Rosmarinic Acid Attenuates Rotenone-Induced Neurotoxicity in SH-SY5Y Parkinson’s Disease Cell Model through Abl Inhibition. Nutrients [Internet]. 2022;14. https://doi.org/10.3390/nu14173508 .
Muthaiah VP, Venkitasamy L, Michael F, Chandrasekar K, Venkatachalam S. Neuroprotective role of naringenin on carbaryl induced neurotoxicity in mouse neuroblastoma cells. J Pharmacol Pharmacother [Internet]. 2013;4:192. https://doi.org/10.4103/0976-500X.114599 .
Kung HC, Lin KJ, Kung C Te, Lin TK. Oxidative Stress, Mitochondrial Dysfunction, and Neuroprotection of Polyphenols with Respect to Resveratrol in Parkinson’s Disease. Biomedicines [Internet]. 2021;9. https://doi.org/10.3390/biomedicines9080918/
Murphy MP. How mitochondria produce reactive oxygen species. Biochemical Journal. 2009;417:1–13.
doi: 10.1042/BJ20081386
pubmed: 19061483
Vasdev N, Handa M, Kesharwani P, Shukla R. Rosemary oil low energy nanoemulsion: optimization, µrheology, in silico, in vitro, and ex vivo characterization. [Internet]. 2022 [cited 2023 Jan 2];33:1901–23. Available from: https://www.tandfonline.com/doi/abs/10.1080/09205063.2022.2088527 .
Trócsányi E, György Z, Zámboriné-Németh É. New insights into rosmarinic acid biosynthesis based on molecular studies. Curr Plant Biol. 2020;23: 100162.
doi: 10.1016/j.cpb.2020.100162
Peng Y, Qu R, Xu S, Bi H, Guo D. Regulatory mechanism and therapeutic potentials of naringin against inflammatory disorders. Heliyon [Internet]. 2024 [cited 2024 Jun 4];10:e24619. Available from: http://www.ncbi.nlm.nih.gov/pubmed/38317884 .
Garabadu D, Agrawal N. Naringin Exhibits Neuroprotection Against Rotenone-Induced Neurotoxicity in Experimental Rodents. Neuromolecular Med [Internet]. 2020 [cited 2024 Jun 4];22:314–30. Available from: https://pubmed.ncbi.nlm.nih.gov/31916219/ .
Zhang G, Sun G, Guan H, Li M, Liu Y, Tian B, et al. Naringenin nanocrystals for improving anti-rheumatoid arthritis activity. Asian J Pharm Sci [Internet]. 2021;16:816. https://doi.org/10.1016/j.ajps.2021.09.001 .
Cui W, He Z, Zhang Y, Fan Q, Feng N. Naringenin Cocrystals Prepared by Solution Crystallization Method for Improving Bioavailability and Anti-hyperlipidemia Effects. AAPS PharmSciTech. 2019;20. https://doi.org/10.1208/s12249-019-1324-0 .
Hoonjan M, Sachdeva G, Chandra S, Kharkar PS, Sahu N, Bhatt P. Investigation of HSA as a biocompatible coating material for arsenic trioxide nanoparticles. Nanoscale [Internet]. 2018 [cited 2024 Jun 4];10:8031–41. Available from: https://pubs.rsc.org/en/content/articlehtml/2018/nr/c7nr09503a .
Megala M, Shivaramakrishnan B, Kishore R. M, Balashanmugam K. Neuroprotective potential of Naringenin-loaded solid-lipid nanoparticles against rotenone-induced Parkinson’s disease model. J Appl Pharm Sci. 2020.
Kesh S, Kannan RR, Balakrishnan A. Naringenin alleviates 6-hydroxydopamine induced Parkinsonism in SHSY5Y cells and zebrafish model. Comp Biochem Physiol C: Toxicol Pharmacol. 2021;239: 108893.
pubmed: 32949818
Dong Z, Wang R, Wang M, Meng Z, Wang X, Han M, et al. Preparation of Naringenin Nanosuspension and Its Antitussive and Expectorant Effects. Molecules 2022, Vol 27, Page 741 [Internet]. 2022 [cited 2024 Jun 29];27:741. Available from: https://www.mdpi.com/1420-3049/27/3/741/htm .
Costa CP, Cunha S, Moreira JN, Silva R, Gil-Martins E, Silva V, et al. Quality by design (QbD) optimization of diazepam-loaded nanostructured lipid carriers (NLC) for nose-to-brain delivery: Toxicological effect of surface charge on human neuronal cells. Int J Pharm. 2021;607.
Simões A, Castro RAE, Veiga F, Vitorino C. A quality by design framework for developing nanocrystal bioenabling formulations. Int J Pharm [Internet]. 2023 [cited 2024 Jun 5];646. Available from: https://pubmed.ncbi.nlm.nih.gov/37717717/ .
Kim HJ, Jeong YS, Hae JP, Park HK, Dong HY, Chung JH. Naringin Protects against Rotenone-induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells. Korean J Physiol Pharmacol [Internet]. 2009;13:281. https://doi.org/10.4196/kjpp.2009.13.4.281 .
Sonia Angeline M, Sarkar A, Anand K, Ambasta RK, Kumar P. Sesamol and naringenin reverse the effect of rotenone-induced PD rat model. Neuroscience [Internet]. 2013 [cited 2024 Jun 5];254:379–94. Available from: https://pubmed.ncbi.nlm.nih.gov/24070629/ .