Polyphenols in the Central Nervous System: Cellular Effects and Liposomal Delivery Approaches
Abstract
1. Introduction
2. Polyphenols as Neuroprotective Agents: Antioxidant Properties, Bioavailability, and Mechanisms of Action
2.1. Bioavailability of Polyphenols and Their Biosafety
2.2. Neuroprotective Mechanisms of Polyphenols’ Action in the Context of Oxidative Stress and Neurodegeneration
3. CNS Cell-Type Specific Effects of Polyphenols in the Central Nervous System
3.1. Neuroprotective Mechanisms of Selected Polyphenols in Neuronal Cells
3.1.1. Neuroprotective Effects of Epigallocatechin-3-Gallate in Neurons
3.1.2. Neuroprotective Effects of Berberine in Neurons
3.1.3. Neuroprotective Effects of Curcumin in Neurons
3.1.4. Neuroprotective Effects of Resveratrol in Neurons
3.1.5. Neuroprotective Effects of Quercetin in Neurons
3.2. Neuroprotective Mechanisms of Selected Polyphenols in Astrocytes
3.3. Neuroprotective Mechanisms of Selected Polyphenols in Microglial Cells
3.3.1. Influence of Curcumin on Microglia During the Course of Neurodegenerative Diseases
3.3.2. Influence of Luteolin on Microglia During the Course of Neurodegenerative Diseases
3.3.3. Influence of Resveratrol on Microglia During the Course of Neurodegenerative Diseases
3.3.4. Influence of Quercetin on Microglia During the Course of Neurodegenerative Diseases
3.4. Neuroprotective Mechanisms of Selected Polyphenols in OPCs and OLs
3.4.1. Influence of Quercetin on OPCs and OLs During the Course of Neurodegenerative Diseases
3.4.2. Influence of Resveratrol and Curcumin on OPCs and OLs During the Course of Neurodegenerative Diseases
3.4.3. Influence of Phloretin and Ellagic Acid on OPCs and OLs During the Course of Neurodegenerative Diseases
3.4.4. The Role of Other Polyphenols in OPCs and OLs Function During Neurodegenerative Diseases
4. Nanodelivery of Polyphenols: Liposomes as a Promising Platform
- Membrane composition adjustments, such as the incorporation of cholesterol, which stabilizes and stiffens the lipid bilayer [220].
- Surface functionalization, e.g., polyethylene glycol (PEG) coating, to prolong circulation time and reduce immune clearance (stealth effect) [214].
- Targeting strategies, involving the conjugation of antibodies or ligands to the liposomal surface, which can direct the nanocarrier to specific tissues or cell types [221].
Advances in Liposomal Nanocarriers for Brain-Targeted Polyphenol Therapy
5. Conclusions and Future Perspective
Author Contributions
Funding
Conflicts of Interest
References
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Polyphenol (Dosage) | Adverse Effect | Study Type | Reference |
---|---|---|---|
Epigallocatechin gallate (379 mg/day for 3 months) | Decreased blood iron levels | Randomized controlled trials, obese patients | [58] |
Quercetin (500 mg/day for 12 weeks) | Decreased blood iron levels | Randomized, double-blind, placebo-controlled study | [59] |
Raspberry and strawberry extracts (50 μg/mL GAE 1) | Significant reduction in lipase activity | In vitro | [60] |
Quercetin (minimal inhibitory concentration = 20–50 µg/mL); Naringenin and hesperetin (minimal inhibitory concentration ≥ 250 µg/mL) | Strong negative impact on physiological intestinal microbiota | In vitro | [61] |
Green tea catechins (630 mg) | Significantly reduced systemic digoxin levels | In vivo human study | [62] |
Grapefruit juice (8 oz, 3× a day for 6 days) | Increased felodipine availability due to CYP3A4 inhibition | In vivo human study | [63] |
Isoflavones (approximately 600 µg/g for 5 weeks) | 35-fold increase in plasma phytoestrogen levels; decreased body and prostate weight | In vivo rat model | [64] |
Soy isoflavones (5 mg/kg) | Elevated blood pressure | Human case study | [65] |
Genistein (270 mg/kg); quercetin (302 mg/kg) | Dose-dependent DNA double-strand break in hematopoietic cells | In vitro model | [66] |
Liposome-Based Composition | Functionalization | Size (nm) | Load | Encapsulation Efficiency (%) | Effect | Model | Source |
---|---|---|---|---|---|---|---|
Phosphatidylserine | - | 132.86 ± 2.05 | EGCG | 70.4 | Increased anti-inflammatory and neuroprotective effects | In vitro/in vivo | [227] |
Liposomes composed of L-α-phosphatidylcholine | - | 155.2 ± 1.23 | EGCG | 55.4 | Increased anti-inflammatory and neuroprotective effects | In vitro/in vivo | [227] |
Liposomes composed of sphingomyelin | - | 97.6 ± 3.1 | Curcumin | 1.3 mol% (with respect to total phospholipid content) | Inhibited formation of Aβ1–42 fibrils | In vitro | [228] |
Liposomes composed of lecithin | - | 146–585 | Resveratrol | 73.54% | Increased dopaminergic neuron protection | In vivo (rat PD model) | [229] |
Liposomes composed of Lipoid S100 | PEG 1 | 100.6 ± 0.7 | Curcumin | 87 ± 3 | Increased bilayer stability; decreased polyphenol release | In vitro | [230] |
Liposomes composed of phosphatidylcholine | PEG 1 | 107.4–116.1 | Copaifera sabulicola leaves extract | 81.89–86.30 | Reduced glioma cell viability by 93% | In vitro | [231] |
Liposomes composed of brain lipids | Anti-TfR Ab 2 | 133.0 ± 27.0 | Polyphenol-rich grape pomace extracts | 20.15 μg/mL of polyphenols in 1 mg/mL of vehicles | Increased protection against neurodegeneration | In vivo (rat PD model) | [232] |
Liposomes composed of egg phosphatidylcholine | Transferrin moieties | 211.2 ± 0.8 | Resveratrol | 70−75 | Increased cytotoxicity and apoptosis in glioblastoma | In vitro/in vivo | [233] |
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Kaluza, M.; Ksiazek-Winiarek, D.; Szpakowski, P.; Czpakowska, J.; Fijalkowska, J.; Glabinski, A. Polyphenols in the Central Nervous System: Cellular Effects and Liposomal Delivery Approaches. Int. J. Mol. Sci. 2025, 26, 6477. https://doi.org/10.3390/ijms26136477
Kaluza M, Ksiazek-Winiarek D, Szpakowski P, Czpakowska J, Fijalkowska J, Glabinski A. Polyphenols in the Central Nervous System: Cellular Effects and Liposomal Delivery Approaches. International Journal of Molecular Sciences. 2025; 26(13):6477. https://doi.org/10.3390/ijms26136477
Chicago/Turabian StyleKaluza, Mateusz, Dominika Ksiazek-Winiarek, Piotr Szpakowski, Joanna Czpakowska, Julia Fijalkowska, and Andrzej Glabinski. 2025. "Polyphenols in the Central Nervous System: Cellular Effects and Liposomal Delivery Approaches" International Journal of Molecular Sciences 26, no. 13: 6477. https://doi.org/10.3390/ijms26136477
APA StyleKaluza, M., Ksiazek-Winiarek, D., Szpakowski, P., Czpakowska, J., Fijalkowska, J., & Glabinski, A. (2025). Polyphenols in the Central Nervous System: Cellular Effects and Liposomal Delivery Approaches. International Journal of Molecular Sciences, 26(13), 6477. https://doi.org/10.3390/ijms26136477