In vitro assessment of the glucose-lowering effects of berberrubine-9-O-beta-D-glucuronide, an active metabolite of berberrubine
Yang, Na1; Sun, Run-Bin1; Chen, Xing-Long2; Zhen, Le1; Ge, Chun1; Zhao, Yu-Qing1; He, Jun1; Geng, Jian-Liang1; Guo, Jia-Hua1; Yu, Xiao-Yi1; Fei, Fei1; Feng, Si-Qi1; Zhu, Xuan-Xuan3; Wang, Hong-Bo4; Fu, Feng-Hua4; Aa, Ji-Ye1; Wang, Guang-Ji
2017-03-01
Source PublicationACTA PHARMACOLOGICA SINICA
Volume38Issue:3Pages:351-361
AbstractBerberrubine (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.
KeywordHyperglycemia Glucose-lowering Effect Berberine Berberrubine Glucuronide Alpha-glycosidase Hfd-induced Hyperglycemia Model Of C57bl/6 Mice Human Normal Liver Cell Line L-o2 Pharmacokinetics
DOI10.1038/aps.2016.120
Indexed BySCI
Language英语
WOS Research AreaChemistry ; Pharmacology & Pharmacy
WOS SubjectChemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS IDWOS:000395792800006
Citation statistics
Cited Times:11[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/51006
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.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
Recommended Citation
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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