Pharmacokinetics, Tissue Distribution, and Metabolic Profile of Cyanidin 3‐O‐β‐Galactoside Purified From Black Chokeberry

Neurodegenerative diseases (NDs) pose a significant public health concern due to their association with cognitive impairment and disrupted brain glucose metabolism. Cyanidin 3-O-β-galactoside (Cy3Gal), an anthocyanin from black chokeberry, exerted neuroprotective effects by modulating brain energy metabolism. This study aims to investigate its absorption, tissue distribution, and metabolic profile. Following a single-dose administration (gavage, 300 mg/kg) to male Sprague-Dawley rats, Cy3Gal reached a peak plasma concentration of 2967.29 ± 556.71 ng/mL within 0.25 h. Pharmacokinetic analysis revealed a short half-life (0.77 ± 0.05 h) and high clearance rate (101.84 ± 23.90 L/h/kg), suggesting a fast distribution and elimination. Twenty metabolites were identified in plasma, including methylated, glucuronidated, and sulfated forms, with varying distribution across rat tissues. Notably, this is the first study to demonstrate that Cy3Gal and its methylated metabolites (peonidin 3-O-galactoside [Peo3Gal]) can cross the blood-brain barrier, which provided strong evidence for the neuroprotective effects. Peo3Gal showed superior protection against high glucose-induced injury compared to Cy3Gal. Additionally, in vitro fermentation with rat gut microbiota uncovered three Cy3Gal-derived metabolites, suggesting microbial involvement in its transformation. Overall, these findings provide critical insights into Cy3Gal's bioavailability and brain accessibility, supporting its potential as a dietary neuroprotective agent.