School of Nursing, Beijing University of Chinese Medicine, Beijing, 100029, China.
School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
J Ethnopharmacol. 2021 Jul 15;275:114107. doi: 10.1016/j.jep.2021.114107. Epub 2021 Apr 14.
Motion sickness is a multi-system syndrome caused by abnormal spatial environmental sensory conflicts. Tianxiang Capsule (TXC) is a traditional Chinese medicine (TCM) formula for the prevention and treatment of motion sickness for years. However, the main active components of TXC and mechanism of its therapeutic effects on motion sickness are still unclear.
The purpose of this work is to investigate the mechanism of TXC in preventing motion sickness based on serum metabolomics and network pharmacology. On the basis of the clear validation of the anti-motion sickness effect of TXC, we used the strategy of combined GC-MS metabolomics and network pharmacology to screen 60 differential metabolites regulated by TXC.
The rat models of motion sickness were stimulated by biaxial rotational acceleration, spontaneous activity was used to evaluate the efficacy of TXC on motion sickness. Serum metabolomics-based analysis was conducted to screen the differential metabolites related to motion sickness. Then, network pharmacology analysis was used to integrate the information of differential metabolites with target proteins and chemical components, and the "components-target protein-metabolite related protein-metabolite" network was constructed to explore the mechanism of the protective effect of TXC against motion sickness.
The results of network integration analysis showed that the 50 TXC potential active ingredients mediated the differential expression of 49 metabolic biomarkers by targeting 25 target protein and regulated arachidonic acid metabolism, calcium signaling pathways, etc. In addition, we found that TXC can promote the secretion of insulin mediated by arachidonic acid pathway metabolites, regulate the levels of adrenaline and leptin, maintain blood glucose balance, and achieve the therapeutic effect of motion sickness.
Our results indicated that the arachidonic acid metabolic pathway and related targets are the key ways for TXC to exert its efficacy, and its target protein and anti-motion sickness mechanism deserve further study. Our work proved that the integrated strategy of metabolomics and network pharmacology can well explain the "multi-component - multi-target" mechanism of complex TCM in vivo, which is a practical approach for the study of TCM formula.
晕动病是一种由异常空间环境感觉冲突引起的多系统综合征。天香胶囊（TXC）是一种传统的中药（TCM）配方，用于预防和治疗晕动病已有多年。然而，TXC 的主要活性成分及其治疗晕动病的机制仍不清楚。
本研究旨在基于血清代谢组学和网络药理学研究 TXC 预防晕动病的机制。在明确 TXC 抗晕动病作用的基础上，我们采用 GC-MS 代谢组学与网络药理学相结合的策略，筛选出 60 种受 TXC 调节的差异代谢产物。
采用双轴旋转加速度刺激晕动病大鼠模型，自发活动评价 TXC 对晕动病的疗效。进行基于血清代谢组学的分析，筛选与晕动病相关的差异代谢物。然后，利用网络药理学分析将差异代谢物与靶蛋白和化学物质的信息进行整合，构建“成分-靶蛋白-代谢物相关蛋白-代谢物”网络，探讨 TXC 防治晕动病的作用机制。
网络整合分析结果表明，50 种 TXC 潜在活性成分通过靶向 25 个靶蛋白介导 49 种代谢生物标志物的差异表达，调节花生四烯酸代谢、钙信号通路等。此外，我们发现 TXC 可以通过花生四烯酸途径代谢物促进胰岛素的分泌，调节肾上腺素和瘦素的水平，维持血糖平衡，从而达到治疗晕动病的效果。
本研究结果表明，花生四烯酸代谢途径和相关靶点是 TXC 发挥疗效的关键途径，其靶蛋白和抗晕动病机制值得进一步研究。我们的工作证明，代谢组学和网络药理学的综合策略可以很好地解释体内复杂 TCM 的“多成分-多靶点”机制，是 TCM 配方研究的实用方法。
