Pharmacokinetics and conjugation metabolism of naringin and naringenin in rats after single dose and multiple dose administrations

Naringin and naringenin are major flavonoids in citrus fruits. This study investigated the pharmacokinetics of naringin and naringenin in rats. Single dose of naringenin was administered to rats via intravenous bolus and oral route, whereas naringin was given orally as single dose and multiple doses (twice daily for 9 days). The serum concentrations of naringenin were assayed by HPLC method prior to and after hydrolysis with β-glucuronidase and sulfatase, respectively. After intravenous bolus of naringenin, naringenin sulfates and glucuronides emerged instantaneously, the profile of naringenin parent form declined rapidly. In contrast, when naringenin and naringin was orally administered, naringenin sulfates and glucuronides were found almost exclusively circulating in the bloodstream, whereas no naringin and naringenin was detected in most serum samples. After multiple-dose administration of naringin, naringenin sulfates and glucuronides gradually accumulated in the circulation and reached steady state on day 5. The profile of naringenin sulfates was much higher than that of naringenin glucuronides. In conclusion, the sulfates and glucuronides of naringenin were exclusively present in the circulation whether naringenin or naringin was orally given to rats. Therefore, pharmacologists should focus more on the bioactivities of conjugated metabolites of naringenin, in particular naringenin sulfates.