In vitro assessment of the glucose-lowering effects of berberrubine-9-O-beta-D-glucuronide, an active metabolite of berberrubine

doi:10.1038/aps.2016.120

	In vitro assessment of the glucose-lowering effects of berberrubine-9-O-beta-D-glucuronide, an active metabolite of berberrubine
	Yang, Na 1; Sun, Run-Bin 1; Chen, Xing-Long 2; Zhen, Le 1; Ge, Chun 1; Zhao, Yu-Qing 1; He, Jun1 ; Geng, Jian-Liang 1; Guo, Jia-Hua 1; Yu, Xiao-Yi 1; Fei, Fei 1; Feng, Si-Qi 1; Zhu, Xuan-Xuan 3; Wang, Hong-Bo 4; Fu, Feng-Hua 4; Aa, Ji-Ye 1; Wang, Guang-Ji
	2017-03-01
发表期刊	ACTA PHARMACOLOGICA SINICA
卷号	38 期号:3 页码:351-361
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-beta-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 alpha-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 L-O2 in vitro, treatment with BRB or BRBG (5, 20, 50 ae mol/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-O2 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.
关键词	Hyperglycemia Glucose-lowering Effect Berberine Berberrubine Glucuronide Alpha-glycosidase Hfd-induced Hyperglycemia Model Of C57bl/6 Mice Human Normal Liver Cell Line L-o2 Pharmacokinetics
DOI	10.1038/aps.2016.120
收录类别	SCI
语种	英语
WOS记录号	WOS:000395792800006
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/51006
专题	植物化学与西部植物资源持续利用国家重点实验室
作者单位	1.China Pharmaceut Univ, Key Lab Drug Metab & Pharmacokinet, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Peoples R China 3.Jiangsu Prov Hosp Tradit Chinese Med, Clin Res Inst, Dept Pharmacol, Nanjing 210009, Peoples R China 4.Yantai Univ, Sch Pharm, Collaborat Innovat Ctr Adv Drug Delivery Syst & B, Yantai 264005, Peoples R China
推荐引用方式 GB/T 7714	Yang, Na,Sun, Run-Bin,Chen, Xing-Long,et al. In vitro assessment of the glucose-lowering effects of berberrubine-9-O-beta-D-glucuronide, an active metabolite of berberrubine[J]. ACTA PHARMACOLOGICA SINICA,2017,38(3):351-361.
APA	Yang, Na.,Sun, Run-Bin.,Chen, Xing-Long.,Zhen, Le.,Ge, Chun.,...&Wang, Guang-Ji.(2017).In vitro assessment of the glucose-lowering effects of berberrubine-9-O-beta-D-glucuronide, an active metabolite of berberrubine.ACTA PHARMACOLOGICA SINICA,38(3),351-361.
MLA	Yang, Na,et al."In vitro assessment of the glucose-lowering effects of berberrubine-9-O-beta-D-glucuronide, an active metabolite of berberrubine".ACTA PHARMACOLOGICA SINICA 38.3(2017):351-361.

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