Enhanced Anti-diabetic Effect of Berberine Combined With Timosaponin B2 in Goto-Kakizaki Rats, Associated With Increased Variety and Exposure of Effective Substances Through Intestinal Absorption
文献类型：期刊论文
| 作者 | Tian, Xiaoting1,2; Liu, Fang1,2; Li, Zhixiong1,2 ; Lin, Yunfei1,2; Liu, Huan1,2; Hu, Pei1,2; Chen, Mingcang1,2; Sun, Zhaolin1,2; Xu, Zhou1,2; Zhang, Yiting1,2
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| 刊名 | FRONTIERS IN PHARMACOLOGY
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| 出版日期 | 2019-01-24 |
| 卷号 | 10页码:15 |
| 关键词 | berberine timosaponin B2 diabetes combination treatments drug-drug interaction metabolites hepatic metabolism intestinal absorption |
| ISSN号 | 1663-9812 |
| DOI | 10.3389/fphar.2019.00019 |
| 通讯作者 | Pan, Guoyu(gypan@simm.ac.cn) ; Huang, Chenggang(cghsimm@126.com) |
| 英文摘要 | Objective: Inspired by the traditionally clinical application of herb pair Zhimu-Huangbo to treat diabetes, a combination of plant ingredients, timosaponin B2 (TB-2) and berberine (BBR), was evaluated for their anti-diabetic efficacy and cooperative mechanisms. Methods: The efficacy and pharmacokinetics of orally administered TB-2 (33.3 mg/kg/day), BBR (66.7 mg/kg/day), and TB-2 C BBR (100 mg/kg/day) were evaluated in spontaneously non-obese diabetic Goto-Kakizaki (GK) rats, and metformin (200 mg/kg/day) was used as a positive control. The comparative exposure of the parent drugs, timosaponin A3 (TB-2 metabolite), and M1-M5 (BBR metabolites) was quantified in the portal vein plasma (before hepatic disposition), liver, and systemic plasma (after hepatic disposition) of normal rats on single and combination treatments. Cooperative mechanism of TB-2 and BBR on intestinal absorption and hepatic metabolism was investigated in Caco-2 cells and primary hepatocytes, respectively. Results: After a 6-week experiment, non-fasting and fasting blood glucose levels and oral glucose tolerance test results showed that TB-2 C BBR treatments (100 mg/kg/day) displayed significantly anti-diabetic efficacy in GK rats, comparable to that on metformin treatments. However, no significant improvement was observed on TB-2 or BBR treatments alone. Compared to single treatments, combination treatments led to the increased circulating levels of BBR by 107% in GK rats. In normal rats, the hepatic exposure of BBR, timosaponin A3, and M1-M5 was several hundred folds higher than their circulating levels. Co-administration also improved the levels in the plasma and liver by 41-114% for BBR, 141-230% for TB-2, and 12-282% for M1-M5. In vitro, the interaction between TB-2 and BBR was mediated by intestinal absorption, rather than hepatic metabolism. Conclusion: Combining TB-2 and BBR enhanced the anti-diabetic efficacy by increasing the in vivo variety of effective substances, including the parent compounds and active metabolites, and improving the levels of those substances through intestinal absorption. This study is a new attempt to assess the effects of combined plant ingredients on diabetes by scientifically utilizing clinical experience of an herb pair. |
| WOS关键词 | ACTIVATED PROTEIN-KINASE ; IN-VITRO ; METABOLITE-NORATHYRIOL ; POTENTIAL INTERACTION ; MAJOR ALKALOIDS ; PHARMACOKINETICS ; IDENTIFICATION ; DECOCTION ; THERAPY ; MAGNOFLORINE |
| 资助项目 | National Natural Science Foundation of China[81030065] ; National Natural Science Foundation for Young Scientists of China[81603280] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2018ZX09731016-003] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2018ZX09201001-001-008] ; strategic priority research program of Chinese Academy of Sciences[XDA16020200] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000456736400001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/290744]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Pan, Guoyu; Huang, Chenggang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu, Sichuan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Tian, Xiaoting,Liu, Fang,Li, Zhixiong,et al. Enhanced Anti-diabetic Effect of Berberine Combined With Timosaponin B2 in Goto-Kakizaki Rats, Associated With Increased Variety and Exposure of Effective Substances Through Intestinal Absorption[J]. FRONTIERS IN PHARMACOLOGY,2019,10:15. |
| APA | Tian, Xiaoting.,Liu, Fang.,Li, Zhixiong.,Lin, Yunfei.,Liu, Huan.,...&Huang, Chenggang.(2019).Enhanced Anti-diabetic Effect of Berberine Combined With Timosaponin B2 in Goto-Kakizaki Rats, Associated With Increased Variety and Exposure of Effective Substances Through Intestinal Absorption.FRONTIERS IN PHARMACOLOGY,10,15. |
| MLA | Tian, Xiaoting,et al."Enhanced Anti-diabetic Effect of Berberine Combined With Timosaponin B2 in Goto-Kakizaki Rats, Associated With Increased Variety and Exposure of Effective Substances Through Intestinal Absorption".FRONTIERS IN PHARMACOLOGY 10(2019):15. |
入库方式： OAI收割
来源：上海药物研究所
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