In Vitro Protective Effects of Resveratrol-Loaded Pluronic Micelles Against Hydrogen Peroxide-Induced Oxidative Damage in U87MG Glioblastoma Cells
Source abstract
Abstract
Numerous studies reported that resveratrol (RVT) exhibits strong antioxidant and cytoprotective effects in brain pathologies, but its low solubility and bioavailability limit its therapeutic potential. Encapsulation of RVT in nanoparticles offers a promising strategy to enhance its effectiveness. The aim of this study was to evaluate the in vitro cytoprotective, DNA protective, and antioxidant capacity of resveratrol-loaded Pluronic (P123/F127) micelles. The effects of micellar (mRVT, water dispersion) and pure RVT (30% hydroethanolic solution) were compared in glioblastoma U87MG cells with H2O2-induced oxidative damage. The cells were pretreated with mRVT or pure RVT (1, 3, 10, and 30 µM) for 24 h before cell damage. The cell viability, DNA damage, acetylcholine esterase (AChE) inhibitory activity, and some biomarkers for oxidative stress like lipid peroxidation (LPO), superoxide dismutase (SOD), and catalase (CAT) were evaluated. In addition, the cellular uptake efficiency of the micelles (50 nm) was tracked using red fluorescent rhodamine B as a marker. Our findings revealed that the micelles were localized in the cytoplasm of U87MG cells within 1 h of incubation. Empty micelles, mRVT, and RVT did not reduce the viability of U87MG cells after 24 h incubation and protect them from H2O2 exposure. The most effective treatment was with mRVT (1 and 3 µM), which significantly reduced the DNA damage index, maintained LPO levels close to the control, and normalized the activities of AChE, SOD, and CAT that were disrupted by H2O2 treatment. These promising results highlight the feasibility and advantages of using resveratrol-loaded nanoparticles for therapeutic applications.
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Research context
OpenAlex topics: Neurological Disease Mechanisms and Treatments · Sirtuins and Resveratrol in Medicine · Nanoplatforms for cancer theranostics
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Institute of Molecular Biology “Acad. R. Tsanev”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria
Funding
Bulgarian National Science Fund
References (85)
Show source-provided references
1. Oxidative stress, glutamate, and neurodegenerative disorders10.1126/science.7901908 ↗
2. Metabolism and functions of glutathione in brain10.1016/S0301-0082(99)00060-X ↗
3. Singh, A., Kukreti, R., Saso, L., and Kukreti, S. (2019). Oxidative stress: A key modulator in neurodegenerative diseases. Molecules, 24.10.3390/molecules24081583 ↗
4. Oxidative stress concept updated: Definitions, classifications, and regulatory pathways implicated
5. Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress10.1016/j.redox.2016.12.035 ↗
6. Signal transduction by reactive oxygen species10.1083/jcb.201102095 ↗
7. Scarian, E., Viola, C., Dragoni, F., Di Gerlando, R., Rizzo, B., Diamanti, L., Gagliardi, S., Bordoni, M., and Pansarasa, O. (2024). New insights into oxidative stress and inflammatory response in neurodegenerative diseases. Int. J. Mol. Sci., 25.10.3390/ijms25052698 ↗
8. Oxidative stress and neurodegenerative disorders10.3390/ijms141224438 ↗
9. Zhao, X., Fang, J., Li, S., Gaur, U., Xing, X., Wang, H., and Zheng, W. (2019). Artemisinin attenuated hydrogen peroxide (H2O2)-induced oxidative injury in SH-SY5Y and hippocampal neurons via the activation of AMPK Pathway. Int. J. Mol. Sci., 20.10.3390/ijms20112680 ↗
10. A prochelator activated by hydrogen peroxide prevents metal-induced amyloid-aggregation
11. Determination of ROS associated with the degeneration of dopaminergic neurons during dopamine metabolism10.3109/10715760903456084 ↗
12. Vascular pro-oxidant effects related to the autoxidation of dopamine10.1080/10715760802712608 ↗
13. The protective effect of hypoxic preconditioning on cortical neuronal cultures is associated with increases in the activity of several antioxidant enzymes10.1016/j.brainres.2004.05.031 ↗
14. Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight10.1016/j.biopha.2015.07.025 ↗
15. Mitochondrial Dysfunction and Redox Imbalance as a Diagnostic Marker of “Free Radical Diseases”
16. Nguyen-Thi, P.T., Vo, T.K., Pham, T.H.T., Nguyen, T.T., and Van Vo, G. (2024). Natural flavonoids as potential therapeutics in the management of Alzheimer’s disease: A review. 3 Biotech, 14.10.1007/s13205-024-03925-8 ↗
17. Of the phenolic substances of white hellebore (Veratrum grandiflorum Loes. fil.)
18. The cell membrane is the main target of resveratrol as shown by interdisciplinary biomolecular/cellular and biophysical approaches10.1007/s00232-013-9604-1 ↗
19. Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans10.1155/2015/837042 ↗
20. Neurons from senescence-accelerated SAMP8 mice are protected against frailty by the sirtuin 1 promoting agents melatonin and resveratrol10.1111/j.1600-079X.2011.00939.x ↗
21. Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo10.1111/j.1349-7006.2009.01415.x ↗
22. Minireview: Biological effects of resveratrol10.1016/S0024-3205(99)00410-5 ↗
23. Antioxidant effects of resveratrol in cardiovascular, cerebral and metabolic diseases10.1016/j.fct.2013.07.021 ↗
24. Resveratrol Protects Oxidative Stress-Induced Intestinal Epithelial Barrier Dysfunction by Upregulating Heme Oxygenase-1 Expression10.1007/s10620-016-4184-4 ↗
25. Protective effects of resveratrol on β-amyloid-induced oxidative PC12 cell death10.1016/S0891-5849(03)00062-5 ↗
26. Red wine micronutrients as protective agents in Alzheimer-like induced insult10.1016/S0024-3205(03)00123-1 ↗
27. Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats10.1016/S0024-3205(02)02083-0 ↗
28. Red wine ingredient resveratrol protects frombeta-amyloid neurotoxicity10.1159/000073766 ↗
29. Neuroprotective effects of resveratrol against beta-amyloid-induced neurotoxicity in rat hippo-campal neurons: Involvement of protein kinase C10.1038/sj.bjp.0705688 ↗
30. Protective effect of resveratrol against inflammation, oxidative stress and apoptosis in pancreas of aged SAMP8 mice10.1016/j.exger.2017.01.021 ↗
31. Resveratrol, an antioxidant, protects spinal cord injury in rats by suppressing MAPK pathway10.1016/j.sjbs.2016.10.019 ↗
32. Chemistry, stability and bioavailability of resveratrol10.2174/15734064113096660053 ↗
33. Administration of resveratrol: What formulation solutions to bioavailability limitations?10.1016/j.jconrel.2011.09.083 ↗
34. Stability and solubility of trans-resveratrol are strongly influenced by pH and temperature10.1016/j.ejpb.2015.04.002 ↗
35. Peterle, L., Sanfilippo, S., Borgia, F., Li Pomi, F., Vadalà, R., Costa, R., Cicero, N., and Gangemi, S. (2023). The Role of Nutraceuticals and Functional Foods in Skin Cancer: Mechanisms and Therapeutic Potential. Foods, 12.10.3390/foods12132629 ↗
36. Polymeric micelles in anticancer therapy: Targeting, imaging and triggered release10.1007/s11095-010-0233-4 ↗
37. Pluronic® block copolymers in drug delivery: From micellar nanocontainers to biological response modifiers10.1615/CritRevTherDrugCarrierSyst.v19.i1.10 ↗
38. Stabilized Micelles as Delivery Vehicles for Paclitaxel10.1016/j.ijpharm.2012.06.030 ↗
39. Role of Pluronic F127 Micelles in Enhancing Ocular Delivery of Ciprofloxacin10.1016/j.molliq.2014.09.021 ↗
40. Berberine-Loaded Thiolated Pluronic F127 Polymeric Micelles for Improving Skin Permeation and Retention10.2147/IJN.S270336 ↗
41. Yordanov, Y., Stefanova, D., Spassova, I., Kovacheva, D., Tzankova, V., Konstantinov, S., and Yoncheva, K. (2022). Formulation of Nanomicelles Loaded with Cannabidiol as a Platform for Neuroprotective Therapy. Pharmaceutics, 14.10.3390/pharmaceutics14122625 ↗
42. Hersh, A.M., Alomari, S., and Tyler, B.M. (2022). Crossing the Blood-Brain Barrier: Advances in Nanoparticle Technology for Drug Delivery in Neuro-Oncology. Int. J. Mol. Sci., 23.10.3390/ijms23084153 ↗
43. Lazarova, M., Stefanova, M., Tsvetanova, E., Georgieva, A., Tasheva, K., Radeva, L., and Yoncheva, K. (2024). Resveratrol-Loaded Pluronic Micelles Ameliorate Scopolamine-Induced Cognitive Dysfunction Targeting Acetylcholinesterase Activity and Programmed Cell Death. Int. J. Mol. Sci., 25.10.3390/ijms252312777 ↗
44. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays10.1016/0022-1759(83)90303-4 ↗
45. Anew and rapid colorimetric determination of acetylcholinesterase activity10.1016/0006-2952(61)90145-9 ↗
46. Evaluation of different staining methods and image analyses of the results from a comet assay in human colorectal cancer cells treated with hydrogen peroxide
47. DNA repair as a human biomonitoring tool: Comet assay approaches10.1016/j.mrrev.2019.03.002 ↗
48. Effects of flavonoids and Vitamin C on oxidative DNA damage to human lymphocytes10.1093/ajcn/67.6.1210 ↗
49. Mayne, K., White, J.A., McMurran, C.E., Rivera, F.J., and de la Fuente, A.G. (2020). Aging and neurodegenerative disease: Is the adaptive immune system a friend or foe?. Front. Aging Neurosci., 12.10.3389/fnagi.2020.572090 ↗
50. Olufunmilayo, E.O., Gerke-Duncan, M.B., and Holsinger, R.M.D. (2023). Oxidative stress and antioxidants in neurodegenerative disorders. Antioxidants, 12.10.3390/antiox12020517 ↗
51. He, W.J., Lv, C.H., Chen, Z., Shi, M., Zeng, C.X., Hou, D.X., and Qin, S. (2023). The regulatory effect of phytochemicals on chronic diseases by targeting Nrf2-ARE signaling pathway. Antioxidants, 12.10.3390/antiox12020236 ↗
52. Exploring the efficacy of natural products in alleviating Alzheimer’s disease10.4103/1673-5374.253509 ↗
53. Venkatesan, R., Ji, E., and Kim, S.Y. (2015). Phytochemicals that regulate neurodegenerative disease by targeting neurotrophins: A comprehensive review. BioMed Res. Int., 2015.10.1155/2015/814068 ↗
54. Khan, A., Jahan, S., Alshahrani, S., Alshehri, B.M., Sameer, A.S., Arafah, A., Ahmad, A., and Rehman, M.U. (2021). Phytotherapeutic agents for neurodegenerative disorders: A neuropharmacological review. Phytomedicine, Academic Press.10.1016/B978-0-12-824109-7.00012-1 ↗
55. Neuroprotective effects of natural compounds on neurotoxininduced oxidative stress and cell apoptosis10.1080/1028415X.2020.1840035 ↗
56. Tie, F., Fu, Y., Hu, N., and Wang, H. (2022). Silibinin protects against H2O2-induced oxidative damage in SH-SY5Y cells by improving mitochondrial function. Antioxidants, 11.10.3390/antiox11061101 ↗
57. Orexin-A protects SH-SY5Y cells against H2O2-induced oxidative damage via the PI3K/MEK1/2/ERK1/2 signaling pathway10.1177/2058738418785739 ↗
58. Resveratrol oligomers from vitis amurensis attenuate -amyloid-induced oxidative stress in PC12 cells10.1248/bpb.30.1130 ↗
59. Oxidative stress: Apoptosis in neuronal injury10.2174/156720506778249515 ↗
60. Sies, H. (2020). Oxidative stress: Concept and some practical aspects. Antioxidants, 9.10.3390/antiox9090852 ↗
61. Konno, T., Melo, E.P., Chambers, J.E., and Avezov, E. (2021). Intracellular sources of ROS/H2O2 in health and neurodegeneration: Spotlight on endoplasmic reticulum. Cells, 10.10.3390/cells10020233 ↗
62. Reactive oxygen species and the central nervous system10.1111/j.1471-4159.1992.tb10990.x ↗
63. Possible role of NF-κB in Bcl-XL protection against hydrogen peroxide-induced PC12 cell death10.1179/135100004225006858 ↗
64. DNA damage by oxygen-derived species. Itsmechanism and measurement in mammalian systems10.1016/0014-5793(91)80347-6 ↗
65. Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells10.1016/j.ejphar.2007.01.089 ↗
66. Ascorbate peroxidase-a hydrogen peroxide-scavenging enzyme in plants10.1111/j.1399-3054.1992.tb04728.x ↗
67. Mitochondrial formation of reactive oxygen species10.1113/jphysiol.2003.049478 ↗
68. Lignan compounds and 4,4′-dihydroxybiphenyl protect C2C12 cells against damage from oxidative stress10.1016/j.bbrc.2006.03.107 ↗
69. Beetroot (Beta vulgaris L.) extract ameliorates gentamicin-induced nephrotoxicity associated oxidative stress, inflammation, and apoptosis in rodent model
70. Protective effect beetroot Beta vulgaris extract against H2O2 Induced Oxidative stress in U87MG gliomacells10.38150/sajeb.11(3).p266-274 ↗
71. Resveratrol-loaded polymeric micelles protect cells from Abeta-induced oxidative stress10.1016/j.ijpharm.2009.03.021 ↗
72. Neuroprotective And Cognitive Enhancing Effect Of Methanolic Morus Alba Leaf Fraction In U87mg Cell Lines And Experimental Rat Model
73. Oxidative stress, aging, antioxidant supplementation and their impact on human health: An overview10.1016/j.mad.2022.111707 ↗
74. Resveratrol attenuates oxidative-induced DNA damage in C6 Glioma cells10.1016/j.neuro.2007.03.008 ↗
75. Oligodendroglial cells in culture effectively dispose of exogenous hydrogen peroxide: Comparison with cultured neurones, astroglial and microglial cells10.1046/j.1471-4159.2002.00999.x ↗
76. Cholinesterases: Roles in the brain during health and disease10.2174/1567205054367838 ↗
77. The cholinergic hypothesis of Alzheimer’s disease: A review of progress10.1136/jnnp.66.2.137 ↗
78. Foudah, A.I., Devi, S., Alam, A., Salkini, M.A., and Ross, S.A. (2023). Anticholinergic Effect of Resveratrol with Vitamin E on Scopolamine-Induced Alzheimer’s Disease in Rats: Mechanistic Approach to Prevent Inflammation. Front. Pharmacol., 14.10.3389/fphar.2023.1115721 ↗
79. Deng, Z., Li, Y., Liu, H., Xiao, S., Li, L., Tian, J., Cheng, C., Zhang, G., and Zhang, F. (2019). The role of sirtuin 1 and its activator, resveratrol in osteoarthritis. Biosci. Rep., 39.10.1042/BSR20190189 ↗
80. Resveratrol: A reviewof preclinical studies for human cancer prevention10.1016/j.taap.2006.12.025 ↗
81. Dose-dependent effect of resveratrol on proliferation and apoptosis in endothelial and tumor cell cultures10.1038/emm.2000.16 ↗
82. Phospholipid peroxidation induced by the catechol-Fe31(Cu21) complex: A possible mechanism of nigrostriatal cell damage10.1016/0003-9861(90)90651-E ↗
83. Free radical–Lipid interactions and their pathological consequences10.1016/0163-7827(93)90006-I ↗
84. Prooxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics10.1016/S0300-483X(02)00198-1 ↗
85. The role of iron in oxygen radical mediated lipid peroxidation10.1016/0009-2797(89)90087-2 ↗