Effect of storage periods on flavonoid absorption and P-glycoprotein interaction in Pericarpium Citri Reticulatae ‘Chachi’ flavonoid extracts

Pericarpium Citri Reticulatae ‘Chachi’ (PCR-C), abundant in flavonoids, is traditionally believed to enhance its pharmacological effects with long-term storage. The efficacy of these flavonoids is closely related to their intestinal absorption, which is primarily affected by P-glycoprotein (P-gp). This study explored the interaction between flavonoid absorption and P-gp in PCR-C flavonoid extracts (PCR-CF) over different storage periods using a Caco-2 monolayer model and KB/MDR cells, respectively. The transported concentrations (TC) of key flavonoids-hesperidin, isosinensetin, nobiletin, and tangeretin-significantly varied with the storage duration of PCR-CF. Notably, nobiletin and tangeretin enhanced the TC of these flavonoids by inhibiting P-gp activity, thereby influencing intestinal absorption of PCR-CF with different storage time. These findings provide a scientific basis for the traditional belief that long-stored PCR-C possesses superior medicinal properties.