Protocatechuic Acid Improves Alzheimer's Disease by Regulating the Cholinergic Synaptic Signaling Pathway

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by memory decline and cognitive impairments. The clinical treatments for AD have numerous adverse effects; hence, the exploration of natural products for AD therapy is of significant importance. Protocatechuic acid (PA), a natural phenolic acid, has been shown to possess various pharmacological activities, including anti-inflammatory, antioxidant, and antitumor effects. However, the mechanisms underlying its therapeutic potential for AD remain elusive. This study utilized a β-amyloid (Aβ) injection into the hippocampus of mice as an AD model and L-glu-induced HT-22 cell neurotoxicity and lipopolysaccharides (LPS)-induced cellular neuroinflammation models to assess reactive oxygen species (ROS), JC-1, and relevant biochemical markers. This study examined behavioral, pathological, and inflammatory factors and investigated the molecular mechanisms through transcriptomics, western blot, and molecular docking studies. This study's findings reveal that high-dose PA (50 mg/kg) improves symptoms in AD mice through the cholinergic synaptic signaling pathway. This study indicates that PA is a potential candidate for AD treatment targeting the cholinergic synaptic signaling pathway, providing a lead compound for AD therapy.