Han_2026_Chem.Biodivers_23_e03013

Alzheimer's disease (AD) involves impaired cholinergic neurotransmission, so inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is a major treatment strategy. Vaccinium dunalianum Wight leaf extracts, abundant in caffeoylquinic acids (CQAs), potently inhibit AChE (IC(50) = 0.12 +/- 0.01 mg/mL) and BChE (IC(50) = 0.01 +/- 0.01 mg/mL). Key bioactive compounds include 1-O-caffeoylquinic acid (1-CQA), chlorogenic acid (CGA), neochlorogenic acid (NCGA), and cryptochlorogenic acid (CCGA). All inhibited both enzymes concentration-dependently; 1-CQA was strongest (AChE IC(50) = 0.25 +/- 0.03 microM; BChE IC(50) = 0.10 +/- 0.01 microM), surpassing galantamine. Kinetics and docking showed reversible mixed-type inhibition targeting AChE catalytic and peripheral sites. Fluorescence quenching affirmed high-affinity binding, strongest for 1-CQA. It also showed low cytotoxicity in PC12 cells (>=10 microM). These findings reveal a dual cholinesterase inhibitory mechanism and support CQAs as promising anti-AD agents.