Qiao Xue, Wang Qi, Wang Shuang, Kuang Yi, Li Kai, Song Wei, Ye Min
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Front Pharmacol. 2018 Jun 19;9:622. doi: 10.3389/fphar.2018.00622. eCollection 2018.
Herbal medicines are commonly used as compound formulas in clinical practice to achieve optimal therapeutic effects. However, the combination mechanisms usually lack solid evidence. In this study, we report synergistic interactions through altering pharmacokinetics in Gegen-Qinlian Decoction (GQD), an anti-diabetic Chinese medicine formula. A multi-component pharmacokinetic study of GQD and the single herbs was conducted by simultaneously monitoring 42 major bioactive compounds (markers) in rats plasma using LC/MS/MS within 30 min. GQD could remarkably improve the plasma concentrations of berberine (BER) and other alkaloids in Huang-Lian by at least 30%, and glycyrrhizic acid (GLY) from Gan-Cao played a major role. A Caco-2 cell monolayer test indicated that GLY improved the permeability of BER by inhibiting P-glycoprotein. Although GLY alone did not show observable effects, the co-administration of GLY (ig, 50 or 80 mg/kg) could improve the anti-diabetic effects of berberine (ig, 50 mg/kg) in db/db mice in a dose-dependent manner. The blood glucose decreased by 46.9%, whereas the insulin level increased by 40.8% compared to the control group. This is one of the most systematic studies on the pharmacokinetics of Chinese medicine formulas, and the results demonstrate the significance of pharmacokinetic study in elucidating the combination mechanisms of compound formulas.
草药在临床实践中通常作为复方使用，以达到最佳治疗效果。然而，其组合机制往往缺乏确凿证据。在本研究中，我们报告了通过改变中药方剂葛根芩连汤（GQD）的药代动力学实现的协同相互作用。通过在30分钟内使用LC/MS/MS同时监测大鼠血浆中的42种主要生物活性化合物（标志物），对GQD及其单味药进行了多组分药代动力学研究。GQD可显著提高黄连中小檗碱（BER）和其他生物碱的血浆浓度至少30%，甘草中的甘草酸（GLY）起主要作用。Caco-2细胞单层试验表明，GLY通过抑制P-糖蛋白提高了BER的通透性。虽然单独的GLY未显示出明显效果，但GLY（灌胃，50或80 mg/kg）与小檗碱（灌胃，50 mg/kg）联合给药可剂量依赖性地改善db/db小鼠的抗糖尿病作用。与对照组相比，血糖降低了46.9%，而胰岛素水平升高了40.8%。这是对中药方剂药代动力学最系统的研究之一，结果证明了药代动力学研究在阐明复方组合机制方面的重要性。
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