小儿扶脾颗粒体内原型成分分析及网络药理学研究

Analysis of absorbed constituents and network pharmacology research of Xiaoer Fupi Granules

小儿扶脾颗粒是由经典名方“参苓白术散”精简化裁而来,具有健脾益气、和胃化积的功效,临床中常用来治疗小儿脾胃气虚、运化失职、消化不良等疾病,但是其药效成分及作用机制有待进一步研究。通过整合网络药理学与体内原型成分分析对小儿扶脾颗粒的主要活性成分及其分子作用机制进行研究,有助于增加数据库分析结果的真实与可靠性,为进一步临床精准用药、质控标志物的筛选奠定基础。基于BATMAN-TCM分析平台构建小儿扶脾颗粒“化学成分-靶标”网络,为了验证筛选得到的活性成分,应用UPLC-LTQ-Orbitrap-MS技术对口服给药后大鼠血液及尿液中的药物成分进行分析。进而针对鉴定得到的体内原型成分,利用BATMAN-TCM分析平台构建“体内原型成分-靶标-通路”网络,探讨小儿扶脾颗粒的分子作用机制。基于BATMAN-TCM平台初步分析得到小儿扶脾颗粒6味药材的86个活性成分,其中仅有18.6%的化学成分进一步在大鼠的体内被检测到。利用基于体内分析得到的46个原型成分构建“体内原型成分-靶标-通路”网络,发现小儿扶脾颗粒通过辛酸、十八酸等8个主要活性成分干预胃酸分泌、胰岛素分泌等生物学过程实现健脾和胃的功效。该研究揭示了小儿扶脾颗粒的主要活性成分及其作用机制,为小儿扶脾颗粒物质基础及作用机制研究提供了一定的参考价值。

Xiaoer Fupi Granules, a refined version of the classical prescription Shenling Baizhu Powder, has the effect of invigora-ting spleen, replenishing Qi, harmonizing stomach and resolving accumulation and is commonly used to treat Qi deficiency in spleen and stomach, disordered transportation and transformation, and indigestion of children. However, its medicinal constituents and mechanism remain unclear. We studied the main active constituents and action mechanism of Xiaoer Fupi Granules by integrating network pharmacology and prototype constituent analysis in vivo. This study will help to increase the reliability of database analysis results and lay a foundation for precise medication and mining of quality control markers. On the basis of Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine(BATMAN-TCM), the "key chemical constituents-target" network was constructed. Ultra-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS) was employed to analyze the absorbed constituents in rat urine and plasma, so as to validate the network. Further, we used BATMAN-TCM to construct the "absorbed constituents-target-pathway" network and explore the functioning mechanism of Xiaoer Fupi Granules. A total of 86 chemical constituents of Xiaoer Fupi Granules were predicted via BATMAN-TCM, among which only 18.6% were detected in rat plasma and urine. Accor-ding to the "absorbed constituents-target-pathway" network, 8 chemical constituents such as stearic acid and caprylic acid capable of regulating gastric acid and insulin secretion may be the critical constituents of Xiaoer Fupi Granules in invigorating spleen and harmonizing stomach. This study identified the critical active constituents and predicted the action mechanism of Xiaoer Fupi Granules, providing the reference for the research on the material basis of Xiaoer Fupi Granules.