中文摘要：

Berberrubine (BRB ) 是在 vivo 比 BBR 显示出更强壮的葡萄糖阴沉的效果的 berberine (BBR ) 的主要代谢物。在另一方面， BRB 快速并且广泛地被使产生代射变化进 berberrubine-9-O -- 在在口头的管理以后的老鼠的 D-glucuronide (BRBG ) 。在这研究，我们在老鼠比较了 BRB 和 BRBG 的 pharmacokinetic 性质，并且探索了位于他们的葡萄糖阴沉的活动下面的机制。有导致 HFD 的多糖症的 C57BL/6 老鼠被管理 BRB (50 mg 吗？？

英文摘要：

Berberrubine （BRB） is the primary metabolite of berberine （BBR） that has shown a stronger glucose-lowering effect than BBR in vivo. On the other hand, BRB is quickly and extensively metabolized into berberrubine-9-O-β-D-glucuronide （BRBG） in rats after oral administration. In this study we compared the pharmacokinetic properties of BRB and BRBG in rats, and explored the mechanisms underlying their glucose-lowering activities. C57BL/6 mice with HFD-induced hyperglycemia were administered BRB （50 mg·kg^-1·d^-1, ig） for 6 weeks, which caused greater reduction in the plasma glucose levels than those caused by BBR （120 mg·kg^-1·d^-1） or BRB （25 mg·kg^-1·d^-1）. In addition, BRB dose-dependently decreased the activity of α-glucosidase in gut of the mice. After oral administration of BRB in rats, the exposures of BRBG in plasma at 3 different dosages （10, 40, 80 mg/kg） and in urine at different time intervals （0-4, 4-10, 10-24 h） were dramatically greater than those of BRB. In order to determine the effectiveness of BRBG in reducing glucose levels, we prepared BRBG from the urine pool of rats, and identified and confirmed it through LC-MS-IT-TOF and NMR spectra. In human normal liver cell line 1_-02 in vitro, treatment with BRB or BRBG （5, 20, 50 pmol/L） increased glucose consumption, enhanced glycogenesis, stimulated the uptake of the glucose analog 2-NBDG, and modulated the mRNA levels of glucose-6-phosphatase and hexokinase. However, both BBR and BRB improved 2-NBDG uptake in insulin-resistant L-02 cells, while BRBG has no effect. In conclusion, BRB exerts a stronger glucose-lowering effect than BBR in HFD-induced hyperglycemia mice. Although BRB significantly stimulated the insulin sensitivity and glycolysis in vitro, BRBG may have a greater contribution to the glucose-lowering effect because it has much greater system exposure than BRB after oral administration of BRB. The results suggest that BRBG is a potential agent for reducing glucose levels.