Background

Metabolic syndrome (MetS) is prevalent in patients receiving atypical antipsychotic drugs (AADs), but there are few effective interventions. The Traditional Chinese herbal decoction Liu-Yu-Tang (LYT) has achieved clinical improvement for AAD-induced MetS, but its pharmacological mechanism remains unclear.

Method

A network pharmacology-based method was utilized in this study. First, the TCMSP and SwissTargetPrediction database were used to acquire plasma-absorbed components and putative targets of LYT, respectively. Second, an interaction network between shared targets of LYT and MetS was constructed using STRING online tool. Topological analyses were performed to extract hub gene targets. Finally, we did a pathway analysis of gene targets using the Kyoto Encyclopedia of Genes and Genomes (KEGG) to find biological pathways of LYT.

Results

We obtained 655 putative targets of LYT, 434 known targets of AADs, and 1577 MetS-related gene targets. There are 232 shared targets between LYT and MetS. Interaction network construction and topological analysis yielded 60 hub targets, of which 18 were major hub targets, among which IL-6, IL-8, TNF, PI3K, MAPK, and NF-κB (RELA) are the most important in LYT's treatment of AAD-induced MetS. Pathway enrichment analysis revealed a statistically high significance of the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis and the insulin resistance pathway.

Conclusions

LYT may control activities of the pro-inflammatory cytokines IL-6, IL-8, TNF and the important signal transduction molecules PI3K, MAPKs, and NF-κB (RELA), regulating metabolic disturbance-related pathways like the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis, and the insulin resistance pathway, generating therapeutic effects for AAD-induced MetS.

中文翻译：

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基于网络药理学的非常规抗精神病药物代谢综合征的六豫汤治疗机制探讨

背景

代谢综合征（MetS）在接受非典型抗精神病药物（AADs）的患者中很普遍，但几乎没有有效的干预措施。六玉堂汤对AAD诱发的MetS具有临床改善作用，但其药理机制尚不清楚。

方法

在这项研究中使用了基于网络药理学的方法。首先，TCMSP和SwissTargetPrediction数据库分别用于获取血浆吸收的组分和LYT的假定靶标。其次，利用STRING在线工具建立了LYT和MetS共享目标之间的相互作用网络。进行拓扑分析以提取中心基因靶标。最后，我们使用《京都基因与基因组百科全书》（KEGG）对基因靶点进行了途径分析，以发现LYT的生物学途径。

结果

我们获得了655个LYT推定靶标，434个AAD已知靶标和1577个MetS相关基因靶标。LYT和MetS之间共有232个共享目标。相互作用网络的构建和拓扑分析产生了60个枢纽靶标，其中18个是主要的枢纽标靶，其中IL-6，IL-8，TNF，PI3K，MAPK和NF-κB（RELA）在LYT的治疗中最重要AAD诱导的大都会。途径富集分析显示，AGE-RAGE信号传导途径在糖尿病并发症，脂质和动脉粥样硬化以及胰岛素抵抗途径中具有统计学意义。

结论

LYT可能控制促炎细胞因子IL-6，IL-8，TNF和重要的信号转导分子PI3K，MAPKs和NF-κB（RELA）的活性，调节与AGE-RAGE信号通路等代谢紊乱相关的通路在糖尿病并发症，脂质和动脉粥样硬化以及胰岛素抵抗途径中的作用，对AAD诱导的MetS产生治疗作用。