Integrated network pharmacology analysis and serum metabolomics to reveal the cognitive improvement effect of Bushen Tiansui Formula on Alzheimer's disease.
Integrated network pharmacology analysis and serum metabolomics to reveal the cognitive improvement effect of Bushen Tiansui Formula on Alzheimer's disease.
复制标题
综合网络药理学分析和血清代谢组学揭示补肾天髓方对阿尔茨海默病的认知改善作用。
DOI：
10.1016/j.jep.2019.112371
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发表时间：
2020
影响因子：
5.4
通讯作者：
Weijun Peng
中科院分区：
文献类型：
--
作者：
Zheyu Zhang;Yi Pengji;Jingjing Yang;Jianhua Huang;Panpan Xu;Muli Hu;Chunhu Zhang;Bing Wang;Weijun Peng
补肾天髓方（BSTSF）是临床上用于治疗阿尔茨海默病（AD）多年的传统中药方剂。以前，我们已经部分阐明了BSTSF对AD的治疗作用的机制。本研究采用神经网络药理学和血清代谢组学相结合的方法，进一步研究补肾活血方对AD的治疗作用。材料与方法采用Aβ 1-42注射法建立AD大鼠模型，Morris水迷宫实验观察补肾活血方对AD的治疗作用。其次，应用网络药理学分析方法，对可能与BSTSF作用相关的活性成分和靶基因进行了鉴定。然后，代谢组学的策略已经发展到寻找可能的重要的血清代谢物和代谢途径BSTSF诱导。结果网络药理学分析结果显示，BSTSF治疗AD相关的化合物有37个，潜在的靶基因有64个。功能富集分析表明其作用机制主要与肿瘤坏死因子信号通路和磷脂酰肌醇3激酶/蛋白激酶B信号通路有关。基于代谢组学，78个差异内源性代谢物被鉴定为与BSTSF治疗AD相关的潜在生物标志物。这些代谢产物主要参与亚油酸代谢、α-亚麻酸代谢、甘油磷脂代谢、色氨酸代谢、精氨酸和脯氨酸代谢等相关途径。这些发现与网络药理学analysis.ConclusionsIn结论的结果部分一致，我们的研究结果坚定地支持和加强了目前的理解BSTSF对AD的治疗效果。同时，我们的工作也表明，网络药理学-代谢组学整合策略是研究中药药理作用的有效成分和作用机制的有力手段。
Ethnopharmacological relevanceBushen Tiansui Formula (BSTSF) is a traditional Chinese medicine formula used clinically to treat Alzheimer's disease (AD) for many years. Previously, we have partially elucidated the mechanisms involved in the therapeutic effects of BSTSF on AD. However, the underlying mechanisms remain largely unclear.Aim of the studyThe aim of this study was to further investigate the therapeutic effects of BSTSF on AD using an integrated strategy of network pharmacology and serum metabolomics.Materials and methodsThe rat models of AD were established using Aβ 1–42 injection, and morris water maze test was used to evaluate the efficacy of BSTSF on AD. Next, network pharmacology analysis was applied to identify the active compounds and target genes, which might be responsible for the effect of BSTSF. Then, a metabolomics strategy has been developed to find the possible significant serum metabolites and metabolic pathway induced by BSTSF. Additionally, two parts of the results were integrated to confirm each other.ResultsThe results of the network pharmacology analysis showed 37 compounds and 64 potential target genes related to the treatment of AD with BSTSF. The functional enrichment analysis indicated that the potential mechanism was mainly associated with the tumor necrosis factor signaling pathway and phosphatidylinositol 3 kinase/protein kinase B signaling pathway. Based on metabolomics, 78 differential endogenous metabolites were identified as potential biomarkers related to the BSTSF for treating AD. These metabolites were mainly involved in the relevant pathways of linoleic acid metabolism, α-linolenic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and arginine and proline metabolism. These findings were partly consistent with the findings of the network pharmacology analysis.ConclusionsIn conclusion, our results solidly supported and enhanced out current understanding of the therapeutic effects of BSTSF on AD. Meanwhile, our work revealed that the proposed network pharmacology-integrated metabolomics strategy was a powerful means for identifying active components and mechanisms contributing to the pharmacological effects of traditional Chinese medicine.