Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease
Abstract
:1. Introduction
2. Aβ Peptides and Tau Protein
3. Oxidative-Nitrosative Stress
4. Central Nervous System Inflammation and Integrity Disorders of the Blood–Brain Barrier (BBB)
5. Metabolic Disorders
6. Resveratrol Derivatives with Possible Neuroprotective Effects
6.1. Resveratrol Modified with Selenium Nanoparticles
6.2. Resveratrol Hybrid Compounds
6.3. Melinjo and Gnetin C Extracts
7. Conclusions
Funding
Conflicts of Interest
References
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Subject of the Study | Dose | Effect | Reference |
---|---|---|---|
Streptozotocin-induced Alzheimer’s dementia model in Wistar rats | 10 i 20 mg/kg of resveratrol per day i.p. | ↑glutathione in brain | [17] |
Sprague–Dawley rats with AD | 100 µM i.c.v. | ↑HO-1 ↓iNOS in hippocampus | [18] |
ICR mice with AD | 40 mg/kg of resveratrol per day | ↓PDE4A5,4B1,4D3 expression ↑BDNF ↑pCREB ↑PKA ↑BCl-2 expression ↓BAX expression ↓IL-1β, IL-6 in hippocampus | [19] |
People with mild or moderate AD | max 2 g/day of resveratrol | ↓Aβ40 in plasma and in cerebrospinal fluid resveratrol safe and well tolerated | [20] |
People with mild or moderate AD | max 2 g/day of resveratrol | ↓MMP-9 in cerebrospinal fluid | [21] |
Healthy overweight elderly man (BMI 25–30 kg/m2) | 200 mg/day of resveratrol 320 mg of quercetin | ↑memory performance ↑functional connectivity (FC) of the hippocampus ↓HbA1c in serum | [22] |
People with mild or moderate AD | 5 mg resveratrol 5 g malate 5 g dextrose/twice a day | resveratrol safe and well tolerated | [23] |
Wistar rats | 10 mg/kg of resveratrol per day | ↑serum BDNF | [24] |
AβPP/PS1 mouse model of AD | 16 mg/kg of resveratrol per day | ↑synaptophysin ↑mitochondrial IV complex protein in brain | [25] |
Mouse model of AD induced by Aβ1–42 | 0.02 mg/kg of resveratrol per day for cerebral ventricle | ↑AMPK ↑PGC-1 ↓NF-κB / IL-1β / NLRP3 in hippocampus and prefrontal cortex | [26] |
Triple-transgenic mouse model of AD (3 x Tg-AD) | 100 mg/kg of resveratrol per day | ↑neprilisine ↓BACE1 ↑AMPK ↑PGC-1 ↑pCREB in hippocampus | [27] |
APP/PS1 mouse model of AD | 350 mg/kg resveratrol once a day | inhibition of microglia activation by Aβ in brain | [28] |
Compound Symbol | Resveratrol Hybrid | References |
---|---|---|
B | [89] | |
C | [90] | |
D | [91] | |
E | [92] |
Resveratrol Derivatives in MSE | Chemical Structure of Resveratrol Dimer Derivatives |
---|---|
Trans-resveratrol Trans-piceid Isorhapontigenin | resveratrol |
Resveratrol Dimers: GC: Gnetin C GL: Gnetin L GMA: Gnemonoside A GMC: Gnemonoside C GMD: Gnemonoside D | GC: R1 = R3 = R4 = H, R2 = OH GL: R1 = OCH3, R2 = R4 = H, R3 = OH GMA: R1 = R3 = H, R2 = OGlc, R4 = Glc GMC: R1 = R3 = R4 = H, R2 = OGlc GMD: R1 = R3 = H, R2 = OH, R4 = Glc |
Subject of Study | Dose (p.o) | Duration of Treatment | Effect | Reference |
---|---|---|---|---|
Healthy man | 750 mg/day of MSE powder (>20% resveratrol derivatives, including only 0.75 mg/day of resveratrol) | 8 weeks | ↑HDL ↓uric acid in serum | [104] |
Diet-induced obesity mouse model | High-fat diet (HFD) + 2.0% MSE | 8 weeks | ↓weight gain ↓insulin in blood ↓HOMA-IR | [109] |
Healthy person | 150 mg/day of Gnetin C | 2 weeks | ↓uric acid ↓HDL ↓LDL ↓adiponectin in serum well tolerated | [110] |
Healthy person | 320 mg/day of MSE (262 mg (2.57%) of Gnetin C 5.8 mg (0.09%) of trans-resveratrol) | 28 days | ↑serum antioxidant activity well tolerated | [111] |
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Wiciński, M.; Domanowska, A.; Wódkiewicz, E.; Malinowski, B. Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease. Int. J. Mol. Sci. 2020, 21, 2749. https://doi.org/10.3390/ijms21082749
Wiciński M, Domanowska A, Wódkiewicz E, Malinowski B. Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease. International Journal of Molecular Sciences. 2020; 21(8):2749. https://doi.org/10.3390/ijms21082749
Chicago/Turabian StyleWiciński, Michał, Anna Domanowska, Eryk Wódkiewicz, and Bartosz Malinowski. 2020. "Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease" International Journal of Molecular Sciences 21, no. 8: 2749. https://doi.org/10.3390/ijms21082749