Degree of polymerization determines the absorption, metabolic fate, and urinary disposition of procyanidins in rats: A pharmacokinetic and metabolomic study.

Abstract

The bioactivity of procyanidins (PCs) is closely associated with their degree of polymerization (DP), yet the pharmacokinetic mechanisms underlying these DP-dependent effects remain unclear. In this study, comparative pharmacokinetic and metabolomic analyses were performed in rats following gavage (250 mg/kg) of monomeric (-)-epicatechin (EC), dimeric procyanidin B2 (PCB2), and trimeric procyanidin C1 (PCC1). Systemic exposure and urinary recovery of intact PCs decreased progressively with increasing DP, with EC showing the highest plasma exposure (AUC0-48 h = 7975 μg·h/L) and 48 h urinary excretion (221.54 μg). In contrast, PCB2 produced the highest levels of depolymerization-derived flavan-3-ol monomers in plasma, yielding a combined EC and catechin AUC0-48 h of 1266.21 μg·h/L, suggesting enhanced metabolic conversion of dimeric PCs in vivo. Metabolomics further revealed that PCB2-derived metabolites exhibited greater plasma retention but lower urinary elimination than those detected in EC and PCC1 groups. PCC1 showed minimal absorption and excretion, indicating limited bioavailability of highly polymerized PCs. Collectively, this study reveals distinct DP-dependent pharmacokinetic and metabolic profiles of PCs and provides new insights into the structure-metabolism relationships of flavan-3-ols.