Ginkgolides and bilobalide for treatment of Alzheimer's disease and COVID-19: potential mechanisms of action.

ABSTRACT

Alzheimer's disease (AD) is an irreversible degenerative illness of the central nervous system with characteristic histological alterations, known as amyloid plaques and neurofibrillary tangles (NFT). Aggregation of plaques and tangles in the brain induces neurotoxicity and synaptic dysfunction, eventually contributing to neuronal cell death and neurodegeneration. Recent studies have revealed that COVID-19 has a great impact on the development of AD, directly or indirectly, by facilitating the accumulation of amyloid plaques, causing altered functional brain integrity or increasing the phosphorylation rate of tau protein. As two important bioactive components of Ginkgo biloba extract (GbE), ginkgolides and bilobalide (BB) have been reported to show neuroprotective effects in AD via multiple mechanisms such as anti-excitotoxicity, anti-inflammatory and anti-oxidative activities. Intriguingly, ginkgolides and BB also seem to demonstrate antiviral properties against COVID-19 by inhibiting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. Herein, we review studies on the neuroprotective and antiviral mechanisms of ginkgolides and bilobalide, as well as their therapeutic potential against AD and COVID-19.