School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Nutrients. 2022 Dec 11;14(24):5278. doi: 10.3390/nu14245278.
Glycyrrhizinic acid (GL) is clinically applied to treat liver injury, and the bioavailability of orally administered GL is closely related to the gut microbiota. Therefore, the dysbiosis of gut flora in liver injury could significantly influence GL bioavailability. Still, less is known about the impact of probiotic supplementation on the bio-absorption process of oral medication, especially under a pathological state. Herein, probiotic R0011 (R0011) with a high viability in the harsh gastrointestinal environment was selected, and the effect of R0011 on the GL bioavailability in rats was investigated. Four groups of rats ( = 6 per group) were included: the normal group (N group), the normal group supplemented with R0011 (NLGG group), CCl4-induced chronic liver injury model (M group), and the model group supplemented with R0011 (MLGG group). Our results showed that liver injury was successfully induced in the M and MLGG groups via an intraperitoneal injection of 50% (/) CCl4 solution. Healthy rats supplemented with R0011 could increase the bioavailability of GL by 1.4-fold compared with the normal group by plasma pharmacokinetic analysis. Moreover, the GL bioavailability of MLGG group was significantly increased by 4.5-fold compared with the model group. R0011 directly improved gut microbial glucuronidase and downregulated the host intestinal drug transporter gene expression of multidrug resistance protein 2 (MRP2). More critically, R0011 restored the gut microbiota composition and regulated the metabolic function, significantly enhancing the microbial tryptophan metabolic pathway compared with the pathological state, which may indirectly promote the bioavailability of GL. Overall, these data may provide possible strategies by which to address the low bioavailability of traditional medicine through probiotic intervention.
甘草酸(GL)在临床上用于治疗肝损伤,而口服 GL 的生物利用度与肠道微生物群密切相关。因此,肝损伤时肠道菌群失调会显著影响 GL 的生物利用度。然而,关于益生菌补充对口服药物生物吸收过程的影响知之甚少,尤其是在病理状态下。在此,选择了一种在恶劣的胃肠道环境中具有高存活率的益生菌 R0011(R0011),并研究了 R0011 对大鼠 GL 生物利用度的影响。将 4 组大鼠(每组 6 只)纳入研究:正常组(N 组)、正常组添加 R0011(NLGG 组)、四氯化碳(CCl4)诱导的慢性肝损伤模型组(M 组)和模型组添加 R0011(MLGG 组)。结果显示,通过腹腔注射 50%(/)CCl4 溶液成功诱导 M 和 MLGG 组大鼠肝损伤。与正常组相比,健康大鼠补充 R0011 可通过血浆药代动力学分析将 GL 的生物利用度提高 1.4 倍。此外,与模型组相比,MLGG 组的 GL 生物利用度显著提高了 4.5 倍。R0011 可直接提高肠道微生物β-葡萄糖醛酸苷酶的活性,并下调多药耐药蛋白 2(MRP2)的宿主肠内药物转运体基因表达。更重要的是,R0011 恢复了肠道微生物群落组成,并调节了代谢功能,与病理状态相比,显著增强了微生物色氨酸代谢途径,这可能间接促进了 GL 的生物利用度。总之,这些数据可能为通过益生菌干预解决传统药物生物利用度低的问题提供了可能的策略。