A metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of orally administered berberine.
A metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of orally administered berberine.
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DOI：
10.1039/c4mb00500g
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发表时间：
2015-02
影响因子：
--
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Gu S;Cao B;Sun R;Tang Y;Paletta JL;Wu X;Liu L;Zha W;Zhao C;Li Y;Ridlon JM;Hylemon PB;Zhou H;Aa J;Wang G
临床和动物实验表明，口服黄连素具有明显的降脂作用。然而，药代动力学研究表明，小檗碱在体内吸收不良，因此血液和靶组织中的小檗碱水平远低于所揭示的有效浓度。为探讨小檗碱降血脂的作用机制，采用高脂饮食诱导仓鼠高脂血症模型，研究小檗碱对生物系统的影响。我们的研究结果表明，胃内给药的小檗碱吸收到循环和大多数小檗碱积累在肠道内容物。小檗碱胃内给药的生物利用度虽远低于腹腔给药，但其降脂作用较强，提示胃肠道是小檗碱降血脂作用的潜在靶点。对血清和肠道内容物的代谢组学研究表明，口服小檗碱显著调节参与脂质代谢的分子，并增加高血压模型中胆汁酸的产生。DNA分析显示，口服小檗碱调节肠道微生物群，BBR对胆酸向脱氧胆酸的7α-脱羟基转化显示出显著抑制作用，表明肠道中胆汁酸的消除减少。然而，在模型仓鼠中，胆汁酸升高未能以负反馈方式下调CYP 7A 1的表达和功能。提示黄连素的降胆固醇作用可能与其调节胆汁酸代谢和法尼醇X受体信号通路有关。
Clinic and animal studies demonstrated that oral-administrated berberine had distinct lipid-lowering effect. However, pharmacokinetic studies showed berberine was poorly absorbed into the body so that the levels of berberine in the blood and target tissues were far below the effective concentrations revealed. To probe the underlying mechanism, the effect of berberine on biological system was studied on a high-fat-diet-induced hamster hyperlipidemia model. Our results showed that intragastric-administered berberine was poorly absorbed into circulation and most berberine accumulated in gut content. Although the bioavailability for intragastric-administered berberine was much lower than that of intraperitoneal-administered berberine, it had stronger lipid-lowing effect, indicating gastrointestinal is a potential target for hypolipidemic effect of berberine. Metabolomic study on both serum and gut content showed that oral-administrated berberine significantly regulated molecules involved in lipid metabolism, and increased the generation of bile acids in the hyperlipidemic model. DNA analysis revealed that the oral-administered berberine modulated the gut microbiota, and BBR showed a significant inhibition on the 7α-dehydroxylation conversion of cholic acid to deoxycholic acid, indicating a decreased elimination of bile acids in the gut. However, in model hamsters, elevated bile acids failed to down-regulate the expression and function of CYP7A1 in a negative feed-back way. It was suggested that the hypocholesterolemic effect for oral-administrated berberine is involved in its effect on modulating the turnover of bile acids and farnesoid X receptor signal pathway.
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DOI：
10.1152/ajpendo.90710.2008
发表时间：
2009-04-01
影响因子：
5.1
作者：
Kim, Woo Sik;Lee, Yun Sok;Kim, Jae Bum
通讯作者：
Kim, Jae Bum
影响因子：
7.4
作者：
Jiye, A;Trygg, J;Moritz, T
通讯作者：
Moritz, T
影响因子：
3.1
作者：
Burcelin, Remy;Luche, Elodie;Amar, Jacques
通讯作者：
Amar, Jacques
影响因子：
3.6
作者：
Jiang, Zhangjian;Liu, Feng;Li, Sam Fong Yau
通讯作者：
Li, Sam Fong Yau
影响因子：
2.6
作者：
Kitahara, M;Sakata, S;Benno, Y
通讯作者：
Benno, Y