Cui Dong-Ni, Wang Xu, Chen Jia-Qing, Lv Bo, Zhang Pei, Zhang Wei, Zhang Zun-Jian, Xu Feng-Guo
MOE Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical UniversityNanjing, China.
State Key Laboratory of Natural Medicine, China Pharmaceutical UniversityNanjing, China.
Front Pharmacol. 2017 Apr 21;8:211. doi: 10.3389/fphar.2017.00211. eCollection 2017.
Huangqin decoction (HQD), a traditional Chinese medicine (TCM), has been widely used to treat gastrointestinal syndrome in China for thousands of years. Chemotherapy drug irinotecan (CPT-11) is used clinically to treat various kinds of cancers but limited by its side effects, especially delayed diarrhea. Nowadays, HQD has been proved to be effective in attenuating the intestinal toxicity induced by CPT-11. HQD consists of four medicinal herbs including Georgi, Fisch, Pall, and Mill. Due to its complexity, the role of each herb and the multi-herb synergistic effects of the formula are poorly understood. In order to quantitatively assess the compatibility effects of HQD, mass spectrometry-based untargeted metabolomics studies were performed. The serum metabolic profiles of rats administered with HQD, single decoction, -free decoction and baicalin/baicalein combination were compared. A time-dependent trajectory upon principal component analysis was firstly used to visualize the overall differences. Then metabolites deregulation score and relative area under the curve were calculated and used as parameters to quantitatively evaluate the compatibility effects of HQD from the aspect of global metabolic profile and the specifically altered metabolites, respectively. The collective results indicated that played a crucial role in the therapeutic effect of HQD on irinotecan-induced diarrhea. Both HQD and SS decoction regulated glycine, serine and threonine pathway. This study demonstrated that metabolomics was a promising tool to elucidate the compatibility effects of TCM or combinatorial drugs.
黄芩汤（HQD）是一种传统中药，在中国已被广泛用于治疗胃肠综合征数千年。化疗药物伊立替康（CPT-11）临床上用于治疗各种癌症，但受其副作用限制，尤其是延迟性腹泻。如今，已证明HQD在减轻CPT-11诱导的肠道毒性方面有效。HQD由四种草药组成，包括黄芩、芍药、甘草和大枣。由于其成分复杂，每种草药的作用以及该方剂的多草药协同作用尚不清楚。为了定量评估HQD的配伍效果，进行了基于质谱的非靶向代谢组学研究。比较了给予HQD、单味药汤、去甘草汤和黄芩苷/黄芩素组合的大鼠血清代谢谱。首先使用主成分分析的时间依赖性轨迹来可视化总体差异。然后计算代谢物失调评分和曲线下相对面积，并分别用作从全局代谢谱和特异性改变的代谢物方面定量评估HQD配伍效果的参数。总体结果表明，甘草在HQD对伊立替康诱导的腹泻的治疗作用中起关键作用。HQD和去甘草汤均调节甘氨酸、丝氨酸和苏氨酸途径。本研究表明，代谢组学是阐明中药或组合药物配伍效果的有前途的工具。
