Unraveling the therapeutic efficacy of resveratrol in Alzheimer's disease: an umbrella review of systematic evidence

Abstract

Context: Resveratrol (RV), a natural compound found in grapes, berries, and peanuts, has been extensively studied for its potential in treating Alzheimer's disease (AD). RV has shown promise in inhibiting the formation of beta-amyloid plaques (Aβ) and neurofibrillary tangles (NFTs), protecting against neuronal damage and oxidative stress, reducing inflammation, promoting neuroprotection, and improving the function of the blood-brain barrier (BBB). However, conflicting results have been reported, necessitating a comprehensive umbrella review of systematic reviews to provide an unbiased conclusion on the therapeutic effectiveness of RV in AD.

Objective: The objective of this study was to systematically synthesize and evaluate systematic and meta-analysis reviews investigating the role of RV in AD using data from both human and animal studies.

Data sources and extraction: Of the 34 systematic and meta-analysis reviews examining the association between RV and AD that were collected, six were included in this study based on specific selection criteria. To identify pertinent studies, a comprehensive search was conducted in English-language peer-reviewed journals without any restrictions on the publication date until October 15, 2023. The search was carried out across multiple databases, including Embase, MEDLINE (PubMed), Cochrane Library, Web of Science, and Google Scholar, utilizing appropriate terms relevant to the specific research field. The AMSTAR-2 and ROBIS tools were also used to evaluate the quality and risk of bias of the included systematic reviews, respectively. Two researchers independently extracted and analyzed the data, resolving any discrepancies through consensus. Of note, the study adhered to the PRIOR checklist.

Data analysis: This umbrella review presented robust evidence supporting the positive impacts of RV in AD, irrespective of the specific mechanisms involved. It indeed indicated that all six systematic and meta-analysis reviews unanimously concluded that the consumption of RV can be effective in the treatment of AD.

Conclusion: RV exhibits promising potential for benefiting individuals with AD through various mechanisms. It has been observed to enhance cognitive function, reduce Aβ accumulation, provide neuroprotection, protect the BBB, support mitochondrial function, facilitate synaptic plasticity, stabilize tau proteins, mitigate oxidative stress, and reduce neuroinflammation commonly associated with AD.

Keywords: Alzheimer’s; Beta-amyloid plaques; Cognitive function; Neurofibrillary tangles; Neuroprotection; Resveratrol; Tau proteins.

Fig. 1

The flowchart of the selection of pertinent studies

Fig. 2

Activation of SIRT1 through RV has exhibited a range of potential benefits in brain cells. These benefits encompass neuroprotection against degeneration, increased neuronal survival, improved synaptic plasticity, anti-inflammatory properties, and enhanced blood flow and neurovascular health. RV-induced SIRT1 activation aids in reducing oxidative stress, enhancing mitochondrial function, and facilitating the clearance of toxic protein aggregates like Aβ plaques and tau tangles. Furthermore, SIRT1 plays a critical role in regulating synaptic plasticity and neurogenesis for optimal learning and memory, in particular among those who suffering from AD