Metabolism and Pharmacokinetics of Mangiferin in Conventional Rats, Pseudo-Germ-Free Rats, and Streptozotocin-Induced Diabetic Rats
文献类型：期刊论文
| 作者 | Liu, Huihui1; Wu, Bin1; Pan, Guoyu1 ; He, Lei1; Li, Zhixiong1; Fan, Mingsong1; Jian, Longhai2; Chen, Mingcang1; Wang, Ke2; Huang, Chenggang1
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| 刊名 | DRUG METABOLISM AND DISPOSITION
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| 出版日期 | 2012-11 |
| 卷号 | 40期号:11页码:2109-2118 |
| ISSN号 | 0090-9556 |
| DOI | 10.1124/dmd.112.045849 |
| 文献子类 | Article |
| 英文摘要 | To clarify the role of the intestinal flora in the absorption and metabolism of mangiferin and to elucidate its metabolic fate and pharmacokinetic profile in diabetic rats, a systematic and comparative investigation of the metabolism and pharmacokinetics of mangiferin in conventional rats, pseudo-germ-free rats, and streptozotocin (STZ)-induced diabetic rats was conducted. Forty-eight metabolites of mangiferin were detected and identified in the urine, plasma, and feces after oral administration (400 mg/kg). Mangiferin underwent extensive metabolism in conventional rats and diabetic rats, but the diabetic rats exhibited a greater number of metabolites compared with that of conventional rats. When the intestinal flora were inhibited, deglycosylation of mangiferin and sequential biotransformations would not occur. Pharmacokinetic studies indicated a 2.79- and 2.35-fold increase in the plasma maximum concentration and the area under the concentration-time curve from 0 to 24 h of mangiferin in diabetic rats compared with those for conventional rats, whereas no significant differences were observed between conventional rats and pseudo-germ-free rats. Further real-time quantitative reverse transcription-polymerase chain reaction results indicated that the multidrug resistance (mdr) 1a level in the ileum increased, whereas its level in the duodenum and the mdr1b mRNA levels in the duodenum, jejunum, and ileum decreased in diabetic rats compared with those in conventional rats. With regard to the pseudo-germ-free rats, up-regulated mdr1a mRNA levels and down-regulated mdr1b mRNA levels in the small intestines were observed. The diabetic status induced increased UDP-glucuronosyltransferase (UGT) 1A3, UGT1A8, UGT2B8, and sulfotransferase (SULT) 1A1 mRNA levels and decreased catechol-O-methyltransferase (COMT), UGT2B6, UGT2B12, and SULT1C1 mRNA levels. These results might partially explain the different pharmacokinetic and metabolic disposition of mangiferin among conventional and model rats. |
| WOS关键词 | HUMAN INTESTINAL BACTERIUM ; MASS-SPECTROMETRY ; CYTOCHROME-P450 ; LIVER ; MONOOXYGENASES ; EXPRESSION ; BILIRUBIN ; INSULIN ; MICE |
| 资助项目 | National Natural Science Foundation of China[81030065] ; National Natural Science Foundation of China[81274055] ; National Science & Technology Major Project[2012ZX09301001-001] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000310052500008 |
| 出版者 | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277895]  |
| 专题 | 上海中药现代化研究中心 |
| 通讯作者 | Huang, Chenggang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Shanghai Inst Food & Drug Control, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Huihui,Wu, Bin,Pan, Guoyu,et al. Metabolism and Pharmacokinetics of Mangiferin in Conventional Rats, Pseudo-Germ-Free Rats, and Streptozotocin-Induced Diabetic Rats[J]. DRUG METABOLISM AND DISPOSITION,2012,40(11):2109-2118. |
| APA | Liu, Huihui.,Wu, Bin.,Pan, Guoyu.,He, Lei.,Li, Zhixiong.,...&Huang, Chenggang.(2012).Metabolism and Pharmacokinetics of Mangiferin in Conventional Rats, Pseudo-Germ-Free Rats, and Streptozotocin-Induced Diabetic Rats.DRUG METABOLISM AND DISPOSITION,40(11),2109-2118. |
| MLA | Liu, Huihui,et al."Metabolism and Pharmacokinetics of Mangiferin in Conventional Rats, Pseudo-Germ-Free Rats, and Streptozotocin-Induced Diabetic Rats".DRUG METABOLISM AND DISPOSITION 40.11(2012):2109-2118. |
入库方式： OAI收割
来源：上海药物研究所
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