Mikan-fermented tea enhanced hesperidin bioavailability: In vivo pharmacokinetic and in vitro Caco-2 Cell

Hesperidin, a flavanone glycoside abundantly found in citrus fruits, has been reported to exert a wide range of biological activities, including antioxidant, anti-inflammatory, anti-adipogenic, anti-allergic, anti-carcinogenic, antiviral, insulin-sensitizing, hypolipidemic, neuroprotective, and vasoprotective effects. However, bioactive efficacy is limited by its poor water solubility, low absorption, and restricted bioavailability. In this study, we hypothesized that Mikan-fermented tea could enhance the bioavailability of hesperidin by increasing its solubility. To test this, we evaluated the pharmacokinetics of hesperidin in Sprague-Dawley rats following oral administration of the Mikan-fermented tea. We also investigated the mechanisms underlying its enhanced transport of hesperidin using Caco-2 cell monolayers. Our in vivo results demonstrated that oral administration of Mikan-fermented tea significantly increased the Cmax (~3.6-fold) and AUC0–24 (~2.4-fold) of hesperidin (measured as hesperetin aglycone) compared to hesperidin alone. In vitro transport studies revealed that Mikan-fermented tea promoted basolateral transport and reduced intracellular accumulation of hydrophobic hesperidin in Caco-2 cells, strongly indicating improved intestinal absorption and systemic bioavailability.