Effects of Gut Microflora on Pharmacokinetics of Hesperidin: A Study on Non-Antibiotic and Pseudo-Germ-Free Rats
- Effects of Gut Microflora on Pharmacokinetics of Hesperidin: A Study on Non-Antibiotic and Pseudo-Germ-Free Rats
- Ming Ji Jin; 김운용; 김인숙; 김유리; 김동현; 한상배; 김동현; 권오승; 유혜현
- Hesperidine; Gut Microflora
- Issue Date
- Journal of toxicology and environmental health. Part A
- VOL 73, NO 21-22, 1441-1450
- Hesperidin is a biologically active flavanone glycoside occurring abundantly in citrus fruits.
In the present study, effects of intestinal microflora on pharmacokinetics of hesperidin were
investigated using a pseudo-germ-free rat model treated with antibiotics. After administration
of hesperidin to rats, hesperetin, hesperetin glucuronides, and metabolites postulated to
be eriodictyol, hemoeriodictyol, and their glucuronides were detected in urine while hesperetin
glucuronide was predominantly found in plasma. The plasma concentration–time
profile of hesperetin was compared between non-antibiotic-exposed and pseudo-germ-free
rats administered this compound. The maximal concentration (Cmax) values of hesperetin in
non-antibiotic-exposed and pseudo-germ-free rats were 0.58 and 0.20 μg/ml, respectively,
and area under the curve (AUC) values were 6.3 and 2.8 μg-h/ml, respectively. Thus, systemic
exposure as evidenced by AUC and Cmax was significantly higher in normal compared
to pseudo-germ-free rats. Fecal β-glucosidase activities of non-antibiotic-exposed and pseudo-
germ-free rats were 0.21 and 0.11 nmol/min/mg, while fecal α-rhamnosidase activities
were 0.37 and 0.12 nmol/min/mg, respectively. The rate of hesperidin transformation to
hesperetin was 6.9 and 2.9 nmol/min/g in fecal samples in non-antibiotic-exposed and pseudo-
germ-free rats, respectively. Taken together, these results showed that pharmacokinetic
differences between non-antibiotic-exposed and pseudo-germ-free rats may be attributed to
differing hesperidin uptake, as well as alterations in metabolic activities of intestinal flora.
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