Nebulized seabuckthorn seed oil inhalation attenuates Alzheimer’s disease progression in APP/PS1 mice

Seabuckthorn (Hippophae rhamnoides L.) is known for its medicinal properties in treating various diseases, including neurological conditions. However, the therapeutic effect of inhaled seabuckthorn seed oil (SSO) on Alzheimer's disease (AD) remains not fully understood. This study explores the effects of nebulized inhalation of SSO in 9-month-old APP/PS1 mice over 21 days. The results showed that nebulized SSO improved memory and cognition. Using 7.0T MRI to monitor blood oxygenation level dependent (BOLD) signals revealed that SSO altered the Amplitude of Low Frequency Fluctuations (ALFF) and Regional Homogeneity (ReHo) signaling such as in the amygdala and substantia innominate, and hippocampus. Enzyme-linked immuno sorbent assay (ELISA) and pathological analyses indicated reduced neuroinflammation in plasma and brain, decreased neuronal necrosis, lower β-amyloid (Aβ) protein levels, reduced amyloid deposition, and increased tyrosine hydroxylase activity. Additionally, SSO promoted gut microbiota remodeling by increasing alpha diversity and boosting levels of probiotics such as Verrucomicrobia, Bifidobacterium, Prevotella, and Akkermansia, without adverse effects on lung tissue. Nebulized inhalation of SSO may slow AD progression by modulating inflammation and amyloid deposition. Nebulized inhalation offered a potential method for enhancing drug delivery across the blood-brain barrier with reduced systemic side effects.