Table 1.
Preclinical findings regarding the use of stilbenes in neurological disorders.
| Disease name | Compound name | Study model | Dose/conc. | Findings | Ref. |
|---|---|---|---|---|---|
| Alzheimer's disease | Resveratrol | Mice | 40 mg/kg | Resveratrol reversed Aβ associated memory deficits and controlled neuroinflammation. | (69) |
| Mice | 10 and 20 mg/kg | Resveratrol inhibited the Aβ associated microglial stimulation. | (34) | ||
| Transgenic mice | 100 mg/kg | Improved cognitive functionality and offered neuroprotection against Aβ and tau pathologies. | (37) | ||
| Mice | 0.02 mg/kg | Treatment with resveratrol substantially alleviated biochemical and behavioral abnormalities caused by Aβ1-42. | (70) | ||
| AβPP/PS1 mice | 16 mg/kg | Resveratrol facilitated alterations in inflammatory processes and prohibited memory loss. | (71) | ||
| Tg19959 mice | 300 mg/kg | Resveratrol exhibited a region-specific reduction in the development of plaque. | (72) | ||
| Transgenic 5XFAD mice | 0.1% | Improved the detrimental effect on the brain caused by HFD. | (73) | ||
| HT22 cells | 0.1-20 µM | Treatment with resveratrol prevented AMPK from being phosphorylated. | (74) | ||
| PC12 cells | 20 μM | Resveratrol and other small compounds with comparable conformational selectivity helped identify the epitopes causing Aβ-associated toxicity. | (75) | ||
| C57BL/6J mice | 200 mg/kg | Resveratrol reduced peripheral and cerebral inflammation, metabolic abnormalities, and memory loss in mice. | (36) | ||
| Piceatannol | SH-SY5Y cells | 10-50 μM | Piceatannol outperformed AChE suppressive actions and anti-Aβ self-aggregations. | (40) | |
| PC-12 cells | 5-40 μM | Piceatannol reduced oxidative stress and mitochondrial-associated apoptosis in PC-12 cells, resulting in cytoprotection. | (76) | ||
| bEnd.3 cells | 10-50 μM | Piceatannol decreased cerebral cell endothelial oxidative stress and inflammation in vitro. | (77) | ||
| ε-Viniferin | Transgenic mice | 20 mg/kg | Viniferin decreased brain absorption of [18F]DPA-714 more than resveratrol. | (41) | |
| Transgenic mice | 10 mg/kg | Trans ε-viniferin lowered amyloid size and density and reduced microglia and astrocyte reactivity. | (78) | ||
| Miyabenol C | APP/PS1 mice | 0.6 μg/g | Although miyabenol C did not change the protein levels of the β-secretase BACE1, it inhibited its activity in vivo. | (79) | |
| Pterostilbene | SAMP8 mice | 120 mg/kg | Pterostilbene potentially modulated cognition and cellular stress, possibly due to increased PPAR alpha expression and increased lipophilicity. | (42) | |
| Ampelopsin | Rats | - | Ampelopsin substantially amended memory deficit in AD rats by preventing neuroinflammation. | (43) | |
| C57BL/6 mice | 10 ng/µL | Ampelopsin A improved intrinsic neuronal excitability and neuroprotection. | (80) | ||
| Vitisin A | ICR mice | 0.25-4 μM | Vitisin A decreased scopolamine-induced AChE activity and MDA levels and boosted brain BDNF expressions. | (81) | |
| Oxyresveratrol | Mouse cortical astrocytes | 10 µM | CORT-mediated APP synthesis was dramatically reduced by oxyresveratrol via autophagy. | (44) | |
| BV-2 Cells, Mice | 25 μM, 50-100 mg/kg | Oxyresveratrol reduced neuroinflammation caused by LPS, improving cognition and episodic memory. | (82) | ||
| Parkinson's disease | Resveratrol | SNCA mice | 50 mg/kg | Ameliorated cognitive deficit and reduced neuroinflammation and improved motor functionality |
(45) |
| C57BL/6 mice | 100 mg/kg | Ameliorated cognitive deficit, enhanced iron content, improved motor functionality |
(48) | ||
| Wistar albino rats | 20 mg/kg | Resveratrol decreased brain caspase-3 activity and gene expression in rats to diminish ER stress. | (46) | ||
| Wistar rats | 40 mg/kg | Decreased mitochondria dysfunction, reduced oxidative damage, and improved cognitive functioning. | (83) | ||
| Mice | 50 mg/kg | Improved motor functionality, increased neuronal survival, suppressed neural apoptosis | (84) | ||
| SD rats | 15 and 30 mg/kg | Resveratrol-activated PI3K/Akt to impede 6-OHDA-mediated apoptosis. | (85) | ||
| Balb/c mice | 10 mg/kg | Resveratrol treated group showed lower IL-1β levels and enhanced pAkt/Akt ratio, helping dopamine neuron survival. | (86) | ||
| Wistar rats | 2.5 and 10 mg/kg | Resveratrol maintained dopamine levels. | (87) | ||
| SK-N-SH and SH-SY5Y cells | 25-100 μM | RES mediated the SNHG1/miR-128-3p/SNCA axis to promote cell autophagy and inhibit PD development. | (88) | ||
| mutant D. melanogaster | 0-60 mg/kg | Resveratrol decreased parkin dysfunctional mutation-related oxidative stress and locomotor impairment. | (89) | ||
| Piceatannol | Rats | 10 mg/kg | Piceatannol mostly repaired microscopical changes in nerve axons and recovered typical myelin thickness. | (50) | |
| Rats | - | Post-SAH hippocampal apoptosis, cellular edema, and pyknosis were dramatically decreased. | (90) | ||
| Piceatannol-3′-O-β-D-glucopyranoside | N2a cells, male mice | 3.91-125 μM | Reduced nerve cell apoptosis caused by oxidative stress and damage to mitochondria. | (91) | |
| Pterostilbene | BV-2 and SH-SY5Y cells | 2.5-10 μM | Pterostilbene decreased neuronal apoptosis, oxidative damage, and inflammation. | (51) | |
| Vitisin A | C57BL/6 mice | 1-10 μM | BDNF-CREB signaling upregulation by vitisin A partly protects neurons. | (92) | |
| ε-Viniferin | PC12 cells | 10-9 M | Viniferin inhibited glial-induced neuronal cytotoxicity. | (52) | |
| Oxyresveratrol | Mes23.5 cells | 0-50 μM | The 6-OHDA model was protected by oxyresveratrol, which inhibited ATF4 transcription. | (53) | |
| SH-SY5Y cells | 20 μM | Oxyresveratrol treatment raised 7,8-dihydrobiopterin levels, mostly from tyrosine, phenylalanine, and tryptophan metabolism. | (93) | ||
| Wistar rats | 300 mg/kg | Oxyresveratrol treatment protected dopaminergic neurons and decreased rotenone-induced motor impairment. | (54) | ||
| Cerebral ischemia | Resveratrol | Rats | 10 and 100 mg/kg | Resveratrol decreased BBB disruption, inflammation, and brain injury | (59) |
| C57BL/6 mice | 200 mg/kg | Resveratrol prevented post-stroke BBB disturbance, decreased brain infarcts, and lowered neurological impairments. | (60) | ||
| Mice | 30 mg/kg | SIRT1 stimulation may explain resveratrol postconditioning's neuroprotective effects. | (94) | ||
| Rats | 30 mg/kg | Resveratrol administration lowered neurological impairment scores, improved neuronal stem survival, and prevented microglia and astrocyte stimulation. | (95) | ||
| Wistar female rats | 0.15 mg/kg | Resveratrol administration effectively decreased hypoxic-ischemic offspring brain damage. | (96) | ||
| C57/BL mice | 100 mg/kg | Resveratrol inhibited miR-155 to increase microglia M2 polarization and reduce neurological inflammation after cerebral ischemia. | (61) | ||
| SD rats | 10-30 mg/kg | Resveratrol improved neurological performance, infarct area, and cortical ischemia in brain infarction rats. | (97) | ||
| SD rats | 30 mg/kg | Resveratrol mitigated neuronal apoptosis in brain ischemia caused by MCAO. | (98) | ||
| Wistar rats | 1.9 mg/kg | Resveratrol lowered infarct size, cerebral edema, and BBB impairment, improving neurological function and survival rate. | (99) | ||
| Rats | 20 mg/kg | Resveratrol administration substantially decreased lipid peroxidation and hazardous Pb levels in cerebral ischemia rats. | (63) | ||
| Rats | 1.8 mg/Kg | Resveratrol decreased infarct size and improved MCAO-treated rat mortality. | (64) | ||
| Mice | - | Resveratrol improved hippocampus neuronal structure, dendritic spine density, and synaptic protein expression. | (65) | ||
| SD Rats | 10 mg/kg | Resveratrol restored mitochondrial metabolism, improving hcNPC therapeutic effectiveness and neural differentiation. | (100) | ||
| Wistar rats | 1.9 mg/kg | Resveratrol protects neurons from ischemia-associated injury and inhibits GLUT3 overexpression in brains. | (101) | ||
| Wistar rats | 60 mg/kg | Resveratrol reduces oxidative damage, ER stress, and neurological inflammation to prevent subarachnoid hemorrhage. | (102) | ||
| Mice | - | RES reduced the CD147/MMP-9 axis to suppress pro-inflammatory microglia, preventing ischemic brain damage. | (103) | ||
| SD rats | 20 mg/kg | Resveratrol inhibited transition elements, lipid peroxidation, and toxic metals to prevent brain ischemia damage. | (104) | ||
| Rats | 10 mg/kg | Resveratrol downregulated the ERK pathway to decrease IR-induced neuronal death in cerebral hemorrhage models. | (105) | ||
| Rats | - | Resveratrol administration reduced ferroptosis in neurons. | (106) | ||
| C57Bl/6J mice | - | Resveratrol improves memory and protects memory-processing brain regions. | (107) | ||
| Pterostilbene | Rats | 25 mg/kg | Pterostilbene's anti-inflammatory activity protected rats from brain ischemia. | (66) | |
| SD rats | 7-28 mg/kg | Pterostilbene reduced neuronal scores, brain-H2O content, and infarction volume. | (108) | ||
| C57BL/6 mice | 10 mg/kg and 20 mg/kg | Pterostilbene protected hippocampus neurons via Sirt1/FoxO1. | (67) | ||
| ICR mice, PC12 cell | 2.5-40 μM | Piceatannol dramatically upregulated HO-1, Nrf2, and NQO1. | (68) | ||
| Piceatannol | Rats | 1-10 mg/kg | Piceatannol reduced p-JNK3 and neuronal death during ischemia. | (109) | |
| Anxiety and depression | Resveratrol | Rats | 10 and 20 mg/kg | Resveratrol reduced arsenic-related learning and memory impairments in rats. | (110) |
| Wistar rats | 20 mg/kg | Resveratrol lowered anxiety, enhanced burrowing behavior, and decreased spatial memory. | (111) | ||
| Mice | 40 mg/kg | Resveratrol reduced arsenic-associated cognitive impairment. | (112) | ||
| ICR mice | 2.5-10 mg/kg | Resveratrol inhibited PDE4D and activated the cAMP pathway, offering antidepressant effects. | (113) | ||
| ICR mice | 10-40 mg/kg | Resveratrol provided neuroprotection against posttraumatic stress disorder. | (114) | ||
| Wistar rats | 10-40 mg/kg | Resveratrol regulated 5-HT-dependent signaling to strengthen brain functioning. | (115) | ||
| SH-SY5Y cells | 10-25 μM | Resveratrol increased the viability of the cells. | (116) | ||
| SD rats | 10, 30 mg/kg | Resveratrol reduced neuroinflammation. | (117) | ||
| Wistar rats | 20-80 mg/kg | Resveratrol reduced rat feelings of depression and anxiety. | (118) | ||
| C57BL/6 mice | - | Resveratrol reduced depressive actions in mice via activating SIRT1 and autophagy. | (119) | ||
| Wistar rats | 20-80 mg/kg | Resveratrol mitigated depressive responses in animals under stress. | (120) | ||
| Wistar rats | 80 mg/kg | Resveratrol possessed potent antidepressant properties. | (121) | ||
| Pterostilbene | Swiss mice | 50-200 mg/kg | Combining carbamazepine with pterostilbene reduced muscle strength but not motor coordination. | (122) | |
| Mice | 50-200 mg/kg | Pterostilbene decreased seizure events in mice but not locomotion activity or symptoms of anxiety. | (123) | ||
| Piceatannol | Mice | 1-30 mg/kg | Low doses are responsible for the anxiolytic effect | (124) | |
| Autism spectrum disorder | Resveratrol | Wistar rats | 3.6 mg/kg | Resveratrol prevented autistic behavior. | (125) |
| Wistar rats | 3.6 mg/kg | Increased accurate choice percentage. | (126) | ||
| SD rats | 5-15 mg/kg | Resveratrol restored socializing, stereotyping, locomotion, memory, and depression. | (127) | ||
| BTBR model | 20-40 mg/kg | Repetition behavior is reduced. | (128) | ||
| C57BL6/J mice | 30 mg/kg | Resveratrol enhanced social interaction in adult ASD mice after single dosing. | (129) | ||
| Wistar rats | 300 mg/kg | Resveratrol reduced cerebral edema and BBB permeability in ASD animal models. | (130) | ||
| Wistar rats | 3.6 mg/Kg | Resveratrol has been shown to prevent long-term hippocampus changes and regulate interneuron architecture in ASD. | (131) | ||
| Wistar rats | 3.6 mg/Kg | In pups who received VPA during pregnancy, resveratrol avoided developmental delays. | (132) | ||
| Wistar rats | 3.6 mg/kg | Resveratrol mitigated cytoarchitectural and interneuronal alterations. | (133) | ||
| Multiple Sclerosis | Resveratrol | C57/Bl6 mice | 250 mg/kg | Resveratrol protects against neuronal death in persistent demyelinating sickness. | (134) |
| SJL/J mice | 500 mg/kg | Oral SRT501 effectively mitigated the loss of neurons in cases of ocular neuritis. | (135) | ||
| C57Bl/6 mice | 250 mg/kg | Resveratrol enhanced motor coordination, reversed demyelination, enhanced mitochondrial activity, reduced oxidative stress, and suppressed NF-κB activation. | (136) | ||
| Mice | 100 mg/kg | Resveratrol therapy elevated miR-124, decreasing SK1, suggesting immunological regulation. | (137) | ||
| Huntington disease | Resveratrol | Transgenic mice | 25 mg/mouse/day | Resveratrol has been shown to protect against peripheral impairments in HD models. | (56) |
| YAC128 mice | 1 and 5 μM | Resveratrol increased mitochondrial transcription of genes in HD, presumably controlling motor abnormalities. | (57) |