何首乌提取物大鼠体内组织蓄积比较研究

Accumulation of Polygoni Multiflori Radix Extract in Rat Tissues

目的:旨在通过考察何首乌70%乙醇提物(PME)和水提物(PMW)在大鼠体内不同组织的成分蓄积差异,推测何首乌引起不良反应的原因。方法:建立大鼠不同组织中二苯乙烯苷、大黄素和大黄素-8-O-β-D-葡萄糖苷的高效液相色谱串联质谱法(UPLC-MS/MS)定量分析方法;并定量分析连续42 d灌胃PME和PMW后大鼠肝、肾、血浆和胆汁中3个成分的蓄积情况。结果:PME给药组大鼠体内不同组织中相同成分蓄积量明显高于PMW给药组。2个给药组中3个成分选择性蓄积的靶器官基本相同,二苯乙烯苷主要蓄积在肝脏中,大黄素主要蓄积在肾脏中,大黄素-8-O-β-D-葡萄糖苷主要蓄积在胆汁中,而血浆中3个成分的含量均较低。结论:何首乌中二苯乙烯苷、大黄素和大黄素-8-O-β-D-葡萄糖苷在大鼠体内的蓄积情况具有明显的组织选择性。与PMW给药组相比,PME组大鼠给药后体内蓄积成分含量高,可能是其导致临床不良反应的主要原因。其中,二苯乙烯苷大量蓄积于大鼠肝脏中,成为何首乌引发肝损伤的重要潜在毒性物质;大黄素-8-O-β-D-葡萄糖苷主要蓄积在胆汁中,有引发胆汁淤积的风险;大黄素主要蓄积部位为肾脏,其与肝毒性是否直接相关仍需进一步探讨。

Objective:To study the components of 70%ethanol extract(PME)and water extract(PMW)of Polygoni Multiflori Radix in different tissues of rats after administration and predict the reason for the adverse reactions induced by this medicinal material.Methods:The ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was established to determine the content of stilbene glycoside,emodin,and emodin-8-O-β-D-glucoside in different tissues of rats.The accumulation of the three components in rat liver,kidney,plasma,and bile was detected after 42-day gavage of PME and PMW,respectively.Results:The accumulation of each of the three components in different tissues in rats in the PME group was significantly higher than that in the PMW group.High accumulation of stilbene glycoside in the liver,emodin in the kidney,and emodin-8-O-β-D-glucoside in the bile,and low content of the three components in the plasma were detected in both groups.Conclusion:The accumulation of stilbene glycoside,emodin,and emodin-8-O-β-D-glucoside from Polygoni Multiflori Radix is tissue-specific,and the content of the three in the rats which were given PME was higher than that in rats which received PMW,which may explained the adverse reactions induced by PME.The high accumulation of stilbene glycoside in the liver may be the cause of the liver damage by this medicinal material.Moreover,emodin-8-O-β-D-glucoside mainly accumulates in the bile and has the risk of causing cholestasis.In addition,the main accumulation site of emodin is the kidney,so whether it is directly related to liver toxicity still needs to be further explored.