Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Beijing Sihuan Pharmaceutical Co., Ltd., Beijing 100025, PR China.
Tianjin Huanhu Hospital, Tianjin 300350, PR China.
Phytomedicine. 2018 May 15;44:231-238. doi: 10.1016/j.phymed.2018.03.004. Epub 2018 Mar 15.
The massive number of ingredients in traditional Chinese medicines (TCMs) makes quality control very difficult. The concept of quality markers (Q-marker) was recently proposed to evaluate the quality of TCMs. Xuezhiling tablets (XZL) are widely used for the treatment of hyperlipidemia in China owing to its noticeable effectiveness and mild adverse effects, but there are no proper Q-markers for this Chinese patent medicine.
The aim of the present study was to determine the Q-markers of XZL against hyperlipidemia through an integration of investigations on its lipid-lowering effect, metabolomics, content determination and pharmacokinetics.
XZL was prepared in accordance with the method described in the Chinese pharmacopoeia (Ch.P.). Hyperlipidemia was induced in rats through the administration of a high-fat diet (HFD). The hypolipidemic effect of XZL was investigated through the detection of the blood levels of total glyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C). A metabolomics study was conducted to analyze the overall effects of XZL on the regulation of lipid metabolism. The main bioactive compounds of XZL were identified and determined in the XZL preparation and the medicated plasma of hyperlipidemic rats.
XZL lowered the levels of TG, TC, and LDL-C through alterations of metabolic patterns. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucopyranoside (THSG), chrysophanol-1-O-β-glucopyranosyl-(1→3)-O-β-D-glucopyranosy1-(1→6)-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranoside (SHJ), cassiaside, rubrofusarin gentiobioside, aurantio-obtusin, chryso-obtusin, and obtusinfolin were identified and determined both in the preparation and the blood of hyperlipidemic rats.
SHJ, obtusinfolin, THSG, rubrofusarin gentiobioside, and aurantio-obtusin, which are more abundant in the preparation, leading to greater exposure in vivo, were suitable Q-markers to guarantee the medicinal quality of XZL and ensure the clinical effectiveness on hyperlipidemia.
中药（TCM）的成分众多，使得质量控制非常困难。最近提出了质量标志物（Q-marker）的概念，用于评估 TCM 的质量。血滞灵胶囊（XZL）由于其显著的疗效和轻微的不良反应，在中国被广泛用于治疗高血脂症，但这种中药还没有适当的 Q 标志物。
本研究旨在通过对其降脂作用、代谢组学、含量测定和药代动力学的综合研究，确定 XZL 治疗高血脂症的 Q 标志物。
按照中国药典（Ch.P.）描述的方法制备 XZL。通过给予高脂肪饮食（HFD）诱导大鼠高血脂症。通过检测全甘油三酯（TG）、总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）的血液水平来研究 XZL 的降脂作用。进行代谢组学研究，分析 XZL 对脂质代谢调节的整体影响。鉴定和测定 XZL 制剂和高血脂大鼠给药后血浆中的主要生物活性化合物。
XZL 通过改变代谢模式降低 TG、TC 和 LDL-C 水平。2,3,5,4'-四羟基二苯乙烯-2-O-β-D-吡喃葡萄糖苷（THSG）、大黄素-1-O-β-吡喃葡萄糖基-（1→3）-O-β-D-吡喃葡萄糖基-（1→6）-O-β-D-吡喃葡萄糖基-（1→6）-O-β-D-吡喃葡萄糖苷（SHJ）、梓醇、大黄酸龙胆双糖苷、橙皮苷、栀子苷、京尼平苷和京尼平苷酸在制剂和高血脂大鼠血液中均被鉴定和测定。
SHJ、京尼平苷酸、THSG、大黄酸龙胆双糖苷和橙皮苷在制剂中含量更丰富，导致体内暴露量更大，是保证 XZL 药用质量和确保其对高血脂症临床疗效的合适 Q 标志物。
