Table 1.
Natural stilbenes effects in AD: in vivo studies cited in the paper
| Natural stilbenes | Research models | Treatments and doses Effects | References |
|---|---|---|---|
| Trans-resveratrol | Tg199589 mice: transgenic animals expressing APP695 with two familial AD mutations | Orally supplementation with trans-resveratrol at 300 mg/kg from 45 to 90 days. | Karuppagounder et al., 2009 |
| Decrease of plaque deposits, in particular in medial cortex, striatum and hypothalamus. | |||
| 15 week-old male APP/PS1 transgenic mice (B6C3-Tg(APPswe, PSEN1dE9) | Administration of diet supplemented with 0.35% trans-resveratrol during 15 weeks. | Vingtdeux et al., 2010; Capiralla et al., 2012 | |
| Lower amyloid deposition and microglial activation associated with cortical amyloid plaque formation. | |||
| SAMP8 mice (model of sporadic and age-related AD) | Administration of a supplemented with trans-resveratrol (1 g/kg), between 2 months of age and 9 months of age. | Porquet et al., 2013 | |
| Increase of life, activation of AMPK pathways and pro-survival routes (SIRT1). | |||
| Reduction of cognitive impairment. | |||
| Neuroprotective role by decreasing the amyloid burden and reducing tau hyperphosphorylation. | |||
| APP/PS1 mice | Dietary trans-resveratrol treatment. Absence of decrease plaque burden in these mice. Increase of GSK3-β phosphorylation, protein levels of transthyretin and drebrin. |
Varamini et al., 2014 | |
| Adult Sprague-Dawley rats, which are treated by an injection of Aβ25-35 in their lateral ventricle | Combination of the Aβ25–35 treatment with trans-resveratrol. Significant improvement in spatial memory. Reduction in the cellular levels of iNOS and lipid peroxidation and increase in the production of HO-1. |
Huang et al., 2011 | |
| Rat model of AD, established by ovariectomy combined injection of D-galactose (100 mg/kg) | Heart perfusion in vivo with trans-resveratrol at 20, 40 or 80 mg/kg. Decrease in the expression of GFAP at 40 and 80 mg/kg more important with the larger dose of resveratrol. |
Cheng et al., 2015 | |
| Decrease of the TNF-α levels for the three concentrations. | |||
| Rat model of AD, established by ovariectomy combined chronic treatment with D-galactose (one intraperitoneal injection per day of d-gal 100 mg/kg for 12 weeks) | Daily intragastric doses of 20, 40 and 80 mg/kg trans-resveratrol. Protection against spatial memory impairment, by decreasing oxidative stress. |
Zhao et al., 2012 | |
| Rat model of AD, established by ovariectomy combined chronic treatment with D-galactose | Chronic administration of trans-resveratrol at 20, 40 and 80 mg/kg. Decrease of the insoluble Ab42 level in hippocampus by decreasing the expression of NF-κB. Protection of the BBB integrity, by increasing the expression of Claudin-5 and decreasing RAGE and MMP-9 expressions. |
Zhao et al., 2015 | |
| Clinical study: mild to moderate AD patients | Treatment by trans-resveratrol (initially 500 mg once daily with dose escalation ending with 1000 mg twice daily) during 52 weeks. | Turner et al., 2015; Moussa et al., 2017 | |
| Passage of the BBB by resveratrol and its metabolites to exert their effects. | |||
| Safety and good tolerance of resveratrol. | |||
| Decrease of CSF Aβ42 and Aβ40 levels decline but increase of brain volume by resveratrol treatment | |||
| Modulation of neuro-inflammation and decrease of cognitive decline. | |||
| Trans ε-viniferin | Memory loss induced by intracerebroventricular injection with Ab25–35 in mice | Chronic treatment for 7 days with methanol extract (containing notably trans ε-viniferin) at the concentrations of 50 and 100 mg/kg per os. Inhibition of memory loss. |
Jeong et al., 2010 |
| Transgenic APPswePS1dE9 mice | Weekly intraperitoneal injection of trans ε-viniferin at the dose of 10 mg/kg or its vehicle from 3 to 6 months of age. | Caillaud et al., 2019 | |
| Decrease of amyloid deposits and inflammation in the brain of mice. | |||
| Gnetin C Miyabenol C |
Absence of published in vivo studies 12-month-old transgenic APP/PS1 mice |
Intracerebroventricular injection into the lateral ventricle for 3 days at the dose of 0.6 μg/g. | Hu et al., 2015 |
| Reduction of both sAPPβ and soluble Aβ42 and Aβ40 levels in the cortex and hippocampus. | |||
|
Trans-piceid Piceatannol = Astringenin |
Absence of published in vivo studies AD induced in adult male Swiss albino mice by unique intraperitoneal injection of LPS at the dose of 0.8 mg/kg |
Daily intraperitoneal injection of piceatannol at 2.5 mg/kg for 6 days. Amelioration of cognitive status and decrease of cerebral Aβ42 concentration. |
Hassaan et al., 2014 |
| Astringin | Absence of published studies | ||
| Pterostilbene | SAMP8 mice (model of sporadic and age-related AD) | Diet-achievable supplementation of resveratrol or pterostilbene during 2 months | Chang et al., 2012 |
| Improvement by pterostilbene of cognitive status in these mice and decreasing of cellular stress, inflammation and AD markers. | |||
| Learning and memory impairment and changes of microglia and neurons induced in male C57BL/6 mice by bilaterally intrahippocampal injection of LPS | Daily oral administration of pterostilbene at 20 or 40 mg/kg from 7 days before intrahippocampal administration of LPS. Decrease of cognitive disorders. |
Hou et al., 2014 | |
| Anti-inflammatory and neuroprotective role. |
AD: Alzheimer’s disease; Aβ: amyloid-β; AMPK: AMP-activated protein kinase; APP: amyloid precursor protein; BBB: blood-brain barrier; CSF: cerebrospinal fluid; GFAP: glial fibrillary acidic protein; GSK3: glycogen synthase kinase-3; HO-1: heme oxygenase-1; iNOS: induible nitric oxide synthase; LPS: lipopolysaccharide; MMP-9: matrix metalloproteinase 9; NF-κB: nuclear factor κB; RAGE: receptor for advanced glycation end products; sAPPβ: soluble β-fragment of amyloid precusor protein.