Alzheimer’s disease (AD), a neurodegenerative disorder, is one of the leading causes of dementia (Mattsson et al., 2017). At least 15 million people are currently diagnosed with AD globally (Scheltens et al., 2021), and this number is expected to triple by 2050 as the global population ages (Habchi et al., 2016). The first brain regions to be damaged in AD are those responsible for memory, language, and thinking. Therefore, the initial symptoms are frequently a decline in learning and cognitive abilities (Villemagne et al., 2013). The AD is characterized by the extracellular deposition of β-amyloid (Aβ) peptide and the accumulation of hyperphosphorylated microtubule-associated protein tau (Nagata et al., 2018). Aβ plaque deposition is considered the earliest brain change before AD symptoms occur (Tang et al., 2019). Tau accumulation, oxidative stress injury, neuroinflammatory dysfunction, synaptic dysfunction, and neuronal degeneration occur after Aβ oligomerization and aggregation (Reiman et al., 2012, Haass and Selkoe, 2007, Abdelhamid and Nagano, 2023). Eventually, the damage spreads to the brain parts responsible for basic bodily functions, such as swallowing and walking, and causes fatal consequences (Henderson et al., 2014). Currently, AD has demonstrated no effective treatments (Grubman et al., 2021).

Pterostilbene (PTE, trans-3,5-dimethoxy-4'-hydroxystilbene) is a naturally occurring stilbenoid that mainly exists in blueberries and grapes (Kosuru et al., 2016). PTE has many potential health-promoting properties, such as antioxidative stress (Chen et al., 2021), anti-inflammatory (Dellinger et al., 2022), anticancer (Obrador et al., 2021), antiviral (Wu et al., 2023), and antidiabetic (Zhao et al., 2021). Our previous research revealed for the first time that PTE reduces Aβ1–42-induced cognitive impairment and protects hippocampal neurons in mice by inhibiting oxidative stress (Xu et al., 2020), which is a key mechanism of aging and one of the important causes of AD deterioration (Jiang et al., 2016). Therefore, PTE demonstrates potential as a promising therapeutic agent for treating AD. Unfortunately, PTE has the disadvantage of low bioavailability, which may hinder its development and application (Liu et al., 2019). The use of various nanomaterials has largely addressed this issue in recent years.

Nanoemulsion is a biphasic dispersion system (10–200 nm in size) comprising two immiscible liquids: one is a dispersed phase and another is a continuous phase stabilized by incorporating surfactants and cosurfactants (Md et al., 2018). Nanoemulsions can be classified on the basis of their external and internal phases into oil-in-water, water-in-oil, and other types (Handa et al., 2021), and can be used as carriers of drug molecules to improve the solubility of hydrophobic molecules (Tawfik et al., 2023; Jaromin et al., 2020). In addition, nanoemulsions protects encapsulated molecules from enzymatic hydrolysis, controls their release, increases their stability, and improves their bioavailability (Teixé-Roig et al., 2023, Poovaiah et al., 2018). This study primarily developed a nanoemulsion of PTE to improve its therapeutic efficiency. Therefore, we used behavioral tests and oxidative stress markers to investigate the efficiency of PTE loaded on nanocarriers (Gad et al., 2023).