Tissue Distribution Study of Naringin in Rats by Liquid Chromatography-Tandem Mass Spectrometry

Abstract

Naringin (CAS 10236-47-2), a flavanone glucoside widely present in fruits of citrus plants, has received extensive studies on its potential effects on health benefits and was recently demonstrated to be a putative antitussive. In this study, we determined the tissue distributions of naringin and its metabolites (naringenin and naringenin's conjugates) in rats to examine whether they undergo selective uptake by specific organs. Naringin was administered orally to rats at the dose of 42 mg/kg and the concentrations of naringin and its metabolites in tissue compartments were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The areas under curve values in the individual tissues decreased as follows: stomach, small intestine, liver, trachea, muscle, kidney, lung, fat, heart, spleen, ovary, testis, brain for naringin; and liver, stomach, small intestine, kidney, trachea, lung, testis, heart, ovary, fat, spleen, muscle, brain for total naringenin (including free and its conjugates). Naringin and total naringenin were rapidly and widely distributed to all the tissues except brain in rats. They had difficulties in crossing the blood-brain barrier. There are no accumulations in rats. This study identifying naringin in several organs including lung and trachea may explain its effects as antitussive.

Tissue distribution of naringenin conjugated metabolites following repeated dosing of naringin to rats

“…Among assayed organs, the liver contained higher naringenin sulfate and naringenin glucuronide concentrations than other organs, which concurred with previous studies [ 19 ] and indicated these naringenin conjugates have higher protein binding with liver proteins. In the liver, concentration of naringenin sulfates was higher than that of naringenin glucuronides by 240%.…”

Therapeutic effects of naringin in a guinea pig model of ovalbumin-induced cough-variant asthma

“…In pharmacokinetic studies, naringin was administered orally to rats at a dose of 42 mg/kg, which was converted from 36.8 mg/kg in guinea pigs [23,24]. Thus, the middle dose (18.4 mg/kg) was chosen in the present study based on pharmacodynamic and pharmacokinetic studies.…”

Auraptene in the Peels of Citrus kawachiensis (Kawachi Bankan) Ameliorates Lipopolysaccharide‐Induced Inflammation in the Mouse Brain

“…into mice chronically treated with D-galactose lessens their cognitive impairment and mitochondrial dysfunction [22]; and (6) the administration of NGIN (100 mg/kg/day for 16 weeks) to Alzheimer's disease-model mice (APPswe/PS1dE9) improves long-term memory [23]. As NGIN and its metabolites have been shown to have difficulty in crossing the blood-brain barrier (BBB) [24], the BBB might have been destroyed in these cases, consequently permitting NGIN (and probably NRTN) to exert a potent antioxidative effect on the brain.…”