Antidiabetic effects of flavonoids from Sophora flavescens EtOAc extract in type 2 diabetic KK-ay mice | |
Yang, Xinzhou1,2; Yang, Jing1; Xu, Chan1; Huang, Mi1; Zhou, Qi1; Lv, Jingnan1; Ma, Xinhua1; Ke, Changqiang2; Ye, Yang2; Shu, Guangwen1 | |
刊名 | JOURNAL OF ETHNOPHARMACOLOGY |
2015-08-02 | |
卷号 | 171页码:161-170 |
关键词 | Antidiabetic Sophora flavescens KKAy mice GLUT4 AMPK Off-line HPLC-NMR |
ISSN号 | 0378-8741 |
DOI | 10.1016/j.jep.2015.05.043 |
文献子类 | Article |
英文摘要 | Ethnopharmacological relevance: Bitter and cold Chinese medicines have been long used for the treatment for diabetes mellitus (DM) for thousands of years in China. The roots of Sophora flavescens Ait, one of bitter and cold Chinese medicines commonly used to remove lung heat have been used to counteract DM and exerted good clinical effects for diabetic patients in some folk hospitals in Fujian province, PR China. However, the corresponding active principles and antidiabetic mechanism of this Traditional Chinese Medicine remain unclear. Therefore, in this study, we aim at chemical profiling of the active principles, validating the potential antidiabetic effects of the active EtOAc extract (SF-EtOAc) in vitro and in vivo, and elucidating its probable antidiabetic mechanism as well as evaluating its acute oral toxicity. Materials and methods: An off-line semi-preparative LC-NMR and LC-UV-ESI MS protocol was developed to determine the chemical principles of the active EtOAc extract rapidly and unambiguously. The effect of SF-EtOAc on the glucose transporter type 4 (GLUT4) translocation in L6 myotubes was examined. T2DM KK-Ay mice were induced by high-fat diet. SF-EtOAc was orally administration at the dose of 30, 60 and 120 mg/kg/d, for 21 days. Metformin was used as positive control. Body weight, plasma glucose, oral glucose tolerance test, serum insulin and blood-lipid indexes were measured. Phosphorylation of the AMP-activated protein kinase (AMPK) expression in liver was measured. Results: We found that SF-EtOAc significantly improved oral glucose tolerance, increased serum high density lipoprotein cholesterol (HDL-C) and reduced body weight, blood glucose levels and other related blood-lipid indexes. Mechanistically, SF-EtOAc elevated phosphorylation of AMP-activated protein kinase (AMPK) and stimulated membrane translocation of GLUT4. Moreover, it was unveiled that oral median lethal dose (LD50) of SF-EtOAc was more than 7500 mg/kg, suggesting that SF-EtOAc was practically nontoxic for mice. Conclusions: SF-EtOAc improves glucose tolerance, reduces hyperglycemia and resumes insulin levels, at least in part, by activating GLUT4 translocation which may be modulated by AMPK pathway. According to the results of the present study, SF-EtOAc possesses a potent antidiabetic activity and could be used as a safe remedy for the treatment of diabetes. (C) 2015 Elsevier Ireland Ltd. All rights reserved. |
资助项目 | National Natural Science Foundation of China[81102798] ; National Natural Science Foundation of China[31070744] ; State Key Laboratory of Drug Research Foundation[SIMM1403KF-07] ; Wuhan Youth Chenguang Program of Science and Technology[2013070104010028] ; Fundamental Research Funds for the Central Universities[CZY14013] |
WOS关键词 | ACTIVATED PROTEIN-KINASE ; PRENYLATED FLAVONOIDS ; METABOLIC SYNDROME ; INSULIN ACTION ; AMPK ; PREVALENCE ; BERBERINE ; SECONDARY ; OBESITY ; TARGET |
WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
语种 | 英语 |
出版者 | ELSEVIER IRELAND LTD |
WOS记录号 | WOS:000358468000019 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/276442] |
专题 | 天然药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
通讯作者 | Shu, Guangwen |
作者单位 | 1.South Cent Univ Nationalities, Coll Pharm, Wuhan 430074, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201201, Peoples R China |
推荐引用方式 GB/T 7714 | Yang, Xinzhou,Yang, Jing,Xu, Chan,et al. Antidiabetic effects of flavonoids from Sophora flavescens EtOAc extract in type 2 diabetic KK-ay mice[J]. JOURNAL OF ETHNOPHARMACOLOGY,2015,171:161-170. |
APA | Yang, Xinzhou.,Yang, Jing.,Xu, Chan.,Huang, Mi.,Zhou, Qi.,...&Zhao, Ping.(2015).Antidiabetic effects of flavonoids from Sophora flavescens EtOAc extract in type 2 diabetic KK-ay mice.JOURNAL OF ETHNOPHARMACOLOGY,171,161-170. |
MLA | Yang, Xinzhou,et al."Antidiabetic effects of flavonoids from Sophora flavescens EtOAc extract in type 2 diabetic KK-ay mice".JOURNAL OF ETHNOPHARMACOLOGY 171(2015):161-170. |
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