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升陷汤治疗慢性心力衰竭及桔梗的协同作用:代谢组学方法及其应用

Shengxian decoction in chronic heart failure treatment and synergistic property of Platycodonis Radix: a metabolomic approach and its application.

作者信息

Zhang Feng, Zhan Qin, Dong Xin, Jiang Bo, Sun Lianna, Gao Shouhong, He Zhiqing, Tao Xia, Chen WanSheng

机构信息

Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, P.R. China.

出版信息

Mol Biosyst. 2014 Aug;10(8):2055-63. doi: 10.1039/c4mb00055b.

Abstract

Shengxian Decoction (SXT), a classic Traditional Chinese Medicine (TCM) prescription, consists of five TCMs: Astragali Radix, Anemarrhenae Rhizoma, Bupleuri Radix, Platycodonis Radix (PG), and Cimicifugae Rhizoma. SXT has been demonstrated to show good therapeutic effects on the cardiovascular system. A metabolomic approach was applied to study its therapeutic mechanisms and the synergistic properties of PG. UPLC-Q-TOF/MS based metabolomic profiling was adopted to assess the intervention effects of SXT, SXT-PG (SXT lacking PG) and PG, on chronic heart failure (CHF) rats. Betaloc was used as a positive control drug. A supervised discriminant technique (PLS-DA) was used to visualize the difference in global metabolic profiles within all experimental groups. Some significantly changed metabolites, such as carnitines, long-chain fatty acids and sphinganines, were identified, and the biochemical alterations of these were related to the disturbance in serum metabolic profiling of CHF rats. Furthermore, the metabolomics study demonstrated that the administration of SXT, but neither SXT-PG or PG alone, gave satisfactory curative effects on CHF through partially regulating the perturbed metabolic pathways. These observations were demonstrated by histopathological, electrocardiogram and serum enzymatic investigations. All these results supported the TCM theory that PG possesses synergistic properties which promote the synergized herbs in SXT in CHF rats. Overall, this paper demonstrates that metabolomics offers opportunities to understand the therapeutic mechanisms and synergistic properties of TCM.

摘要

升陷汤(SXT)是一首经典的中药方剂,由黄芪、知母、柴胡、桔梗和升麻五味中药组成。已证实SXT对心血管系统具有良好的治疗作用。采用代谢组学方法研究其治疗机制及桔梗的协同作用。采用基于超高效液相色谱-四极杆飞行时间质谱联用(UPLC-Q-TOF/MS)的代谢组学分析方法,评估SXT、缺桔梗的SXT(SXT-PG)及桔梗对慢性心力衰竭(CHF)大鼠的干预作用。倍他乐克用作阳性对照药物。使用有监督的判别技术(偏最小二乘判别分析,PLS-DA)来直观显示所有实验组整体代谢谱的差异。鉴定出一些显著变化的代谢物,如肉碱、长链脂肪酸和鞘氨醇,并且这些代谢物的生化改变与CHF大鼠血清代谢谱的紊乱有关。此外,代谢组学研究表明,给予SXT可通过部分调节紊乱的代谢途径对CHF产生满意的治疗效果,而单独给予SXT-PG或桔梗均无此效果。组织病理学、心电图和血清酶学研究证实了这些观察结果。所有这些结果支持了中医理论,即在CHF大鼠中桔梗具有协同作用,可促进SXT中各味中药协同发挥作用。总体而言,本文表明代谢组学为理解中药的治疗机制和协同作用提供了机会。

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