Li Xing-Xiao, Zhou Zhi-Wei, Zhou Shu-Feng
Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Provincial Cardiovascular Institute, Guangzhou 510080, China.
Drug Metab Lett. 2008 Aug;2(3):223-30. doi: 10.2174/187231208785425746.
The extracts from the root of Salvia miltiorrhiza are widely used in the treatment of angina and stroke. In this study, we have investigated the role of P-glycoprotein (P-gp) in the transport of tanshinone I (TSI), a major active constituent of S. miltiorrhiza. The TSI transport across Caco-2 monolayers was pH-, energy-, and temperature-dependent, but not sodium-dependent. TSI exhibited a polarized transport in Caco-2 monolayers which was attenuated by P-gp inhibitors. The permeability (P(app)) values of TSI in the basolateral to apical direction were significantly higher in MDCK-II cells over-expressing MDR1, as compared to the wild-type control cells. Furthermore, TSI significantly inhibited the transport of digoxin in Caco-2 cells with an IC(50) value of 0.53 +/- 0.09 microM. TSI also moderately stimulated P-gp ATPase activity with K(m) and V(max) values of 31.70 +/- 7.09 microM and 57.71 +/- 5.26 nmol/min/mg protein, respectively. Our findings indicate that TSI is a substrate and inhibitor of P-gp, which has important clinical and toxicological implications.
丹参根提取物被广泛用于治疗心绞痛和中风。在本研究中，我们研究了P-糖蛋白（P-gp）在丹参主要活性成分丹参酮I（TSI）转运中的作用。TSI跨Caco-2单层细胞的转运是pH、能量和温度依赖性的，但不是钠依赖性的。TSI在Caco-2单层细胞中表现出极化转运，这被P-gp抑制剂减弱。与野生型对照细胞相比，过表达MDR1的MDCK-II细胞中TSI从基底外侧到顶端方向的渗透率（P(app)）值显著更高。此外，TSI显著抑制Caco-2细胞中地高辛的转运，IC(50)值为0.53±0.09 microM。TSI还适度刺激P-gp ATPase活性，K(m)和V(max)值分别为31.70±7.09 microM和57.71±5.26 nmol/min/mg蛋白。我们的研究结果表明，TSI是P-gp的底物和抑制剂，这具有重要的临床和毒理学意义。
