Cited by 173Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsBarrier Structure and Function Studies

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Resveratrol Brain Delivery for Neurological Disorders Prevention and Treatment

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Andrade, Stephanie, Ramalho, Maria João, Pereira, Maria do Carmo, Loureiro, Joana A.·2018·Frontiers in Pharmacology

DOI 10.3389/fphar.2018.01261PMC PMC6262174

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Abstract

Resveratrol (RES) is a natural polyphenolic non-flavonoid compound present in grapes, mulberries, peanuts, rhubarb and in several other plants. Numerous health effects have been related with its intake, such as anti-carcinogenic, anti-inflammatory and brain protective effects. The neuroprotective effects of RES in neurological diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases, are related to the protection of neurons against oxidative damage and toxicity, and to the prevention of apoptotic neuronal death. In brain cancer, RES induces cell apoptotic death and inhibits angiogenesis and tumor invasion. Despite its great potential as therapeutic agent for the treatment of several diseases, RES exhibits some limitations. It has poor water solubility and it is chemically instable, being degraded by isomerization once exposed to high temperatures, pH changes, UV light, or certain types of enzymes. Thus, RES has low bioavailability, limiting its biological and pharmacological benefits. To overcome these limitations, RES can be delivered by nanocarriers. This field of nanomedicine studies how the drug administration, pharmacokinetics, and pharmacodynamics are affected by the use of nanosized materials. The role of nanotechnology, in the prevention and treatment of neurological diseases, arises from the necessity to mask the physicochemical properties of therapeutic drugs to prolong the half-life and to be able to cross the blood-brain barrier (BBB). This can be achieved by encapsulating the drug in a nanoparticle (NP), which can be made of different kinds of materials. An increasing trend to encapsulate and direct RES to the brain has been observed. RES has been encapsulated in many different types of nanosystems, as liposomes, lipid and polymeric NPs. Furthermore, some of these nanocarriers have been modified with targeting molecules able to recognize the brain areas. Then, this article aims to overview the RES benefits and limitations in the treatment of neurological diseases, as the different nanotechnology strategies to overcome these limitations.

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“In contrast, resveratrol demonstrates better brain penetration but may require higher doses to achieve therapeutic effects (Andrade et al. 2018).”
The Multidirectional Biological Activity of Resveratrol: Molecular Mechanisms, Systemic Effects and Therapeutic Potential—A Review
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“…come from preclinical studies and are mainly described in qualitative terms, without systematic analysis of the relationship between the effect and the dose and route of administration of resveratrol [92–94,98 In Alzheimer’s disease, resveratrol exhibits multidimensional neuroprotective effects.”
Influential
Resveratrol can inhibit Notch signaling pathway to improve spinal cord injury
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Chitosan Oleate Coated Poly Lactic-Glycolic Acid (PLGA) nanoparticles versus chitosan oleate self-assembled polymeric micelles, loaded with resveratrol.
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“The natural polyphenolic stilbene derivative, Resveratrol, plays a role in neurodegenerative disorders and stimulates AMPK (AMP-activated protein kinase) and autophagy pathway (Andrade et al., 2018).”
Background
Nanobiotechnology in Neurodegenerative Diseases
Jampílek, J., Kráľová, K., Novák, P., & Novák, M. (2019) · Springer eBooks · doi:10.1007/978-3-030-30930-5_4 · Cited by 22
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Single administration of resveratrol improves social behavior in adult mouse models of autism spectrum disorder
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Has resveratrol a potential for mucopolysaccharidosis treatment?
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Resveratrol in Neurodegeneration, in Neurodegenerative Diseases, and in the Redox Biology of the Mitochondria
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“Neuroprotective properties [81–91]: Resveratrol shows promise as a neuroprotective agent due to its multi-faceted mechanisms of action.”
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Resveratrol attenuates chronic social isolation stress‐induced affective disorders: Involvement of NF‐κB/NLRP3 axis
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“So far, this compound has been encapsulated within a variety of nanosystems, such as liposomes, lipid nanoparticles, and polymeric nanoparticles [111].”
Background
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“rhodamine B sulfonyl (LissRhod-PE) [75, 76].”
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“Therefore, various attempts to increase the efficiency of resveratrol delivery to the brain (such as those proposed recently [78, 79]) may be especially important to the development of a true therapy based on this compound.”
Background
Experimental and computational insights into the therapeutic mechanisms of resveratrol in a Drosophila α-synuclein model of Parkinson’s disease
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Neuroprotective Effects of Resveratrol in Ischemic Brain Injury
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“This review summarizes the effects of RSV in nerve regeneration after an ischemic brain injury episode (Figure 1), and it is focused on the published results since 2015, complementing various previous revisions [19,20,29].”
Result
Resveratrol improves the prognosis of rats after spinal cord injury by inhibiting mitogen-activated protein kinases signaling pathway
Kan, S., Liu, C., Zhao, X., Feng, S., Zhu, H., Ma, B., Zhou, M., Fu, X., Hu, W., & Zhu, R. (2023) · Scientific Reports · doi:10.1038/s41598-023-46541-x · Cited by 11
Specific overexpression of SIRT1 in mesenchymal stem cells rescues hematopoiesis niche in BMI1 knockout mice through promoting CXCL12 expression
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“The poor water solubility, rapid elimination (short half-life) and low bioavailability of resveratrol are the main obstacles to making it useful in clinical trials (35).”
Background
Efficacy and Safety of Natural Apigenin Treatment for Alzheimer's Disease: Focus on In vivo Research Advancements
Zhang, N., Nao, J., & Dong, X. (2024) · Current Neuropharmacology · doi:10.2174/1570159x23666241211095018 · Cited by 13
Evaluation of Nanomaterials as Effective Carriers Targeted to Traverse Blood–Brain Barrier for Theragnostics of Neurodegenerative Diseases: An Overview
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Pedroso, J., Schneider, S. E., Lima‐Rezende, C. A., Aguiar, G. P. S., Müller, L. G., de Oliveira, J. V., Piato, Â., & Siebel, A. M. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03656-3 · Cited by 10
Advantages and Disadvantages of Nutraceuticals
Ramamoorthy, R., Melians, M. A., Pon, F. F., Cosio, D. S., Buvarahamurthy, V., Jayakumar, A. R., & Paidas, M. J. (2023) · Nutritional neurosciences · doi:10.1007/978-981-99-0677-2_15 · Cited by 9
Trans-resveratrol electrochemical detection using portable device based on unmodified screen-printed electrode
Klein, R. S., Taniguchi, M. M., dos Santos, P. D., Bonafé, E. G., Martins, A. F., & Monteiro, J. P. (2021) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2021.114399 · Cited by 9
Advancements in nasal drug delivery system of natural products
Hsu, Y., Yang, J., Cao, M., Xu, T., He, J., Hong, H., Jiang, L., Peng, S., & Xiong, P. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1667517 · Cited by 8
Feasibility of a Functional Medicine Approach to Slowing Clinical Cognitive Decline in Patients over Age 55: A Multiple Case Study Report
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“The following is a list of ingredients in the basic supplement panel:  Multivitamin [69,70]  Omega 3 Fatty Acids 860 mg [71-73]  Vitamin K2 45 mcg [74]  Vitamin D 11,000 units [75]  Probiotic 15 Billion CFU: Lactobacillus acidophilus, Bifidobacterium longum, Lactobacillus plantarum plus 15 billion CFU Bifidobacte…”
Background
The Role of Glucose Concentration and Resveratrol in Modulating Neuroinflammatory Cytokines: Insights from an In Vitro Blood–Brain Barrier Model
Komorowska, J., Wątroba, M., Bednarzak, M., Grabowska, A. D., & Szukiewicz, D. (2023) · Medical Science Monitor · doi:10.12659/msm.941044 · Cited by 8
“Furthermore, it has been shown that RSV in the CNS can slow progression of Alzheimer disease [78].”
Background

Authors: Andrade, S., Ramalho, M. J., Pereira, M. D. C., & Loureiro, J. A.
Affiliations: Universidade do Porto (PT)
Corresponding author: Loureiro, Joana A.
ORCID: Ramalho, Maria João
Pereira, Maria do Carmo
Loureiro, Joana A.
Venue: Frontiers in Pharmacology
Publisher: Frontiers Media SA
Published: 2018-11-20
Volume: 9
Pages: 1261-1261
ISSN: 1663-9812 (ISSN-L)
DOI: 10.3389/fphar.2018.01261
PMC: PMC6262174
OpenAlex: W2901539124
Cited by: 173
References: 243
Citations by year: 2026: 19 · 2025: 23 · 2024: 28 · 2023: 16 · 2022: 24 · 2021: 21 · 2020: 26 · 2019: 16
FWCI: 1.04
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: Frontiers in Pharmacology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
Funders: Fundação para a Ciência e a Tecnologia (PD/BD/105984/2014, SFRH/BD/129312/2017, NORTE-01-0145-FEDER-000005 – LEPABE-2 ECO-INNOVATION)
European Regional Development Fund (POCI-01-0145-FEDER-006939, UID/EQU/00511/2013, NORTE-01-0145-FEDER-000005 – LEPABE-2 ECO-INNOVATION)
Topics: Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: resveratrol, brain drug delivery, nanocarriers, blood-brain barrier, neuroprotection, Alzheimer's disease, Parkinson's disease, neurodegenerative diseases, brain cancer, liposomes, polymeric nanoparticles, lipid nanoparticles, drug bioavailability, oxidative stress, apoptosis, angiogenesis inhibition, nanomedicine

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Resveratrol Brain Delivery for Neurological Disorders Prevention and Treatment

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