In vivo pharmacokinetics of hesperidin are affected by treatment with glucosidase-like BglA protein isolated from yeasts
In vivo pharmacokinetics of hesperidin are affected by treatment with glucosidase-like BglA protein isolated from yeasts
复制标题
橙皮苷的体内药代动力学受到从酵母中分离的葡萄糖苷酶样 BglA 蛋白处理的影响
DOI：
10.1021/jf800105c
复制
发表时间：
2008-07-23
影响因子：
6.1
通讯作者：
Zhu, Ze
中科院分区：
文献类型：
--
作者：
Li, Yong-mei;Li, Xiao-mian;Zhu, Ze
橙皮苷是柑橘类水果中含量丰富的黄酮苷，具有广泛的生物活性。但橙皮苷的生物利用度较差。在这里，我们验证了陈皮中的橙皮素比橙皮苷具有更好的生物利用度，并且橙皮苷用葡萄糖苷酶样酵母BglA蛋白处理会提高其生物利用度的假设。结果表明，纯橙皮苷和提取物均可被单孢菌中提取的BglA蛋白水解或在大肠杆菌BL21 （DE3）中表达。这种生物转化影响了总橙皮素在大鼠体内的血浆药代动力学，即给予BglA蛋白处理的橙皮素后，血浆T-max明显短于给予橙皮素提取物后。此外，bgla处理后的橙皮苷总曲线下面积值与口服橙皮苷高4倍，静脉给药橙皮苷高3倍相似。相比之下，服用bgla处理的橙皮苷提取物或纯橙皮苷后，血浆清除率和分布体积明显小于未处理的橙皮苷提取物或纯橙皮苷后。本研究首次系统地同时测定了橙皮苷和橙皮苷的绝对生物利用度，清楚地表明无论给药途径如何，橙皮苷都比橙皮苷具有更高的生物利用度，并表明由于酵母糖苷酶样蛋白BglA的作用，橙皮苷事先通过发酵转化为橙皮苷应显著提高其生物利用度。
Hesperidin is an abundant flavanone glycoside in citrus fruits and has been reported to possess a wide range of biological activities. However, hesperidin has poor bioavailability. Here, we tested the hypothesis that hesperetin found in chenpi will have a better bioavailability than hesperidin and that treatment of hesperidin with the glucosidase-like yeast BglA protein will increase its bioavailability. The results indicate that hesperidin in pure or extract form is hydrolyzed by BglA protein extracted from Sporobolomyces singularis or expressed in Escherichia coli BL21 (DE3). This biotransformation affected the plasma pharmacokinetics of total hesperetin in rats, in that the plasma T-max was significantly shorter after administration of BglA protein-treated hesperidin than after administration of hesperidin extract. In addition, the area under the curve values for total hesperetin after administration of BglA-treated hesperidin were similar to 4-fold higher by oral administration and 3-fold higher by intravenous administration, respectively. In contrast, the plasma clearance value and volume of distribution after administration of BglA-treated hesperidin extract or pure hesperetin were significantly smaller than after administration of untreated hesperidin extract or pure hesperidin. This is the first study that systemically determines the absolute bioavailability of hesperidin and hesperetin simultaneously, shows clearly that hesperetin is more bioavailable than hesperidin regardless of the route of administration, and shows that prior transformation of hesperidin to hesperetin via fermentation should significantly increase its bioavailability because of the action of the yeast glycosidase-like protein BglA.