Yuan Tianjie, Wang Jin, Chen Letian, Shan Jinjun, Di Liuqing
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Jiangsu Engineering Research Centre for Efficient Delivery System of TCM, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Front Microbiol. 2020 Apr 24;11:597. doi: 10.3389/fmicb.2020.00597. eCollection 2020.
Intestinal microbiota has been extensively studied in the context of host health benefit, and it has recently become clear that the gut microbiota influences drug pharmacokinetics and correspondingly efficacy. Intestinal microbiota dysbiosis is closely related with liver cirrhosis, especially the depletion of . Therefore, the bioavailability of orally administered glycyrrhizic acid (GL) was speculated to be influenced under a pathological state. In the present study, was isolated and screened for GL bioconversion capacity . Compared with and , was chosen for further investigation because it has the highest biotransformation rate. Our results showed that could significantly improve the translocation of GL on Caco-2 cell models. Meanwhile, was observed to have the ability to bind with the surface of Caco-2 cells and prominently downregulate the transporter gene expression level of multidrug resistance gene 1 (MDR1) and multidrug resistance protein 2 (MRP2), which were involved in the efflux of drugs. Furthermore, was selected to be orally administred into rats in healthy and liver cirrhosis groups by a daily gavage protocol. Our data highlighted that supplements of significantly improved the bioavailability of orally administered GL in rats, especially under a pathological condition, which may provide a novel strategy for improving the clinical therapeutic effect of liver protective drugs.
肠道微生物群在宿主健康益处方面已得到广泛研究，最近人们清楚地认识到肠道微生物群会影响药物的药代动力学以及相应的疗效。肠道微生物群失调与肝硬化密切相关，尤其是[此处原文缺失相关内容]的耗竭。因此，推测在病理状态下口服甘草酸（GL）的生物利用度会受到影响。在本研究中，分离并筛选了具有GL生物转化能力的[此处原文缺失相关内容]。与[此处原文缺失相关内容]和[此处原文缺失相关内容]相比，[此处原文缺失相关内容]因其具有最高的生物转化率而被选作进一步研究对象。我们的结果表明，[此处原文缺失相关内容]在Caco - 2细胞模型上能显著提高GL的转运。同时，观察到[此处原文缺失相关内容]具有与Caco - 2细胞表面结合的能力，并能显著下调参与药物外排的多药耐药基因1（MDR1）和多药耐药蛋白2（MRP）转运蛋白基因的表达水平。此外，通过每日灌胃方案，将[此处原文缺失相关内容]分别口服给予健康组和肝硬化组大鼠。我们的数据突出表明，补充[此处原文缺失相关内容]能显著提高大鼠口服GL的生物利用度，尤其是在病理状态下，这可能为提高保肝药物的临床治疗效果提供一种新策略。
