School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, PR China; Key Laboratory of Chinese Medicine Formula of Anhui Province, Hefei, 230012, PR China.
The Chinese University of Hong Kong (Shenzhen), Shenzhen, 518172, PR China.
J Ethnopharmacol. 2020 Oct 28;261:113020. doi: 10.1016/j.jep.2020.113020. Epub 2020 Jun 24.
Danggui-Shaoyao-San (DSS), a well-known classic Traditional Chinese medicine (TCM) formula for enhancing Qi (vital energy and spirit), invigorating blood circulation and promoting diuresis, has been widely used in the treatment of nephrotic syndrome (NS). Previously, we have reported some protective effects of DSS against NS, but the in-depth mechanisms remain unclear.
In this study, an ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based urinary metabonomics coupled with bioinformatics method was employed to evaluate the mechanisms of DSS in treating NS from the perspective of metabolism.
The rat models of NS were established using adriamycin injection. The regulative effects of DSS on NS in rats were first assessed by non-targeted metabonomics, which was based on UPLC-Q/TOF-MS. A series of target prediction models were used to predict the target of components identified in DSS and potential metabolites in NS, combined with the experimental results of metabonomics, to construct the biological network.
A total of 16 potential metabolites were screened in NS, of which 13 were significantly regulated by DSS. Metabolic pathway analysis showed that the therapeutic effect of DSS on NS was mainly involved in regulating the amino acid metabolism and energy metabolism. The component-target-metabolites-pathway network revealed 29 targets associated with metabolites that were linked to 27 components of DSS. Bioinformatics analysis showed that the potential targets have various molecular functions (especially serine-type endopeptidase inhibitor activity) and biological process (such as positive regulation of peptidyl-tyrosine phosphorylation or autophosphorylation).
The regulation of disrupted metabolic pathways and the relative targets may be the mechanism for DSS in the treatment of NS. Notably, metabonomics coupled with bioinformatics would be useful to explore the mechanism of DSS against NS and provide better insights on DSS for clinical use.
当归芍药散（DSS），一种著名的传统中药（TCM）配方，用于增强气（活力和精神），活血化瘀，促进利尿，已广泛用于治疗肾病综合征（NS）。此前，我们已经报道了 DSS 对 NS 的一些保护作用，但深入的机制尚不清楚。
本研究采用超高效液相色谱-四极杆飞行时间质谱联用（UPLC-Q/TOF-MS）非靶向代谢组学结合生物信息学方法，从代谢角度评价 DSS 治疗 NS 的机制。
采用阿霉素注射建立 NS 大鼠模型。首先采用基于 UPLC-Q/TOF-MS 的非靶向代谢组学评价 DSS 对 NS 大鼠的调节作用。结合代谢组学实验结果，利用一系列靶标预测模型预测 DSS 成分及 NS 潜在代谢物的靶标，构建生物网络。
共筛选出 NS 中 16 种潜在代谢物，其中 13 种被 DSS 显著调节。代谢途径分析表明，DSS 治疗 NS 的疗效主要涉及调节氨基酸代谢和能量代谢。成分-靶标-代谢物-途径网络显示 29 个与代谢物相关的靶标与 DSS 的 27 个成分相关。生物信息学分析表明，潜在靶点具有多种分子功能（特别是丝氨酸内肽酶抑制剂活性）和生物过程（如肽酪氨酸磷酸化或自身磷酸化的正调控）。
DSS 治疗 NS 的作用机制可能是对失调代谢途径和相关靶标的调节。值得注意的是，代谢组学结合生物信息学方法有助于探索 DSS 治疗 NS 的机制，并为 DSS 的临床应用提供更好的见解。
