Doping Control Center, Korea Institute of Science and Technology, Seoul, Korea.
J Toxicol Environ Health A. 2010;73(21-22):1441-50. doi: 10.1080/15287394.2010.511549.
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 (C(max)) 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 C(max) 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.
橙皮苷是一种生物活性类黄酮糖苷，大量存在于柑橘类水果中。本研究采用抗生素处理的拟无菌大鼠模型，研究了肠道微生物群对橙皮苷药代动力学的影响。橙皮苷给予大鼠后，在尿液中检测到橙皮素、橙皮苷葡萄糖醛酸苷和推测为埃里澳替丁、赫马埃里澳替丁及其葡萄糖醛酸苷的代谢物，而橙皮苷葡萄糖醛酸苷主要存在于血浆中。比较了给予该化合物的非抗生素暴露和拟无菌大鼠的血浆橙皮素浓度-时间曲线。非抗生素暴露和拟无菌大鼠的橙皮素 Cmax 值分别为 0.58 和 0.20μg/ml，AUC 值分别为 6.3 和 2.8μg-h/ml。因此，与拟无菌大鼠相比，正常大鼠的系统暴露（以 AUC 和 Cmax 表示）明显更高。非抗生素暴露和拟无菌大鼠的粪便β-葡萄糖苷酶活性分别为 0.21 和 0.11 nmol/min/mg，粪便α-鼠李糖苷酶活性分别为 0.37 和 0.12 nmol/min/mg。橙皮苷转化为橙皮素的速率分别为非抗生素暴露和拟无菌大鼠粪便样品中的 6.9 和 2.9 nmol/min/g。总之，这些结果表明，非抗生素暴露和拟无菌大鼠之间的药代动力学差异可能归因于橙皮苷摄取的差异以及肠道菌群代谢活性的改变。
