Hoch Matti, Smita Suchi, Cesnulevicius Konstantin, Schultz Myron, Lescheid David, Wolkenhauer Olaf, Gupta Shailendra
Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, 18055, Germany.
Heel GmbH, Baden-Baden, 76532, Germany.
J Inflamm (Lond). 2023 Mar 27;20(1):12. doi: 10.1186/s12950-023-00335-0.
Modifying the acute inflammatory response has wide clinical benefits. Current options include non-steroidal anti-inflammatory drugs (NSAIDs) and therapies that may resolve inflammation. Acute inflammation involves multiple cell types and various processes. We, therefore, investigated whether an immunomodulatory drug that acts simultaneously at multiple sites shows greater potential to resolve acute inflammation more effectively and with fewer side effects than a common anti-inflammatory drug developed as a small molecule for a single target. In this work, we used time-series gene expression profiles from a wound healing mouse model to compare the effects of Traumeel (Tr14), a multicomponent natural product, to diclofenac, a single component NSAID on inflammation resolution.
We advance previous studies by mapping the data onto the "Atlas of Inflammation Resolution", followed by in silico simulations and network analysis. We found that Tr14 acts primarily on the late phase of acute inflammation (during resolution) compared to diclofenac, which suppresses acute inflammation immediately after injury.
Our results provide new insights how network pharmacology of multicomponent drugs may support inflammation resolution in inflammatory conditions.
调节急性炎症反应具有广泛的临床益处。目前的选择包括非甾体抗炎药（NSAIDs）和可能解决炎症的疗法。急性炎症涉及多种细胞类型和各种过程。因此，我们研究了一种在多个位点同时起作用的免疫调节药物是否比作为单一靶点的小分子开发的普通抗炎药更有潜力更有效地解决急性炎症且副作用更少。在这项工作中，我们使用伤口愈合小鼠模型的时间序列基因表达谱来比较多成分天然产物创伤紫（Tr14）与单成分NSAIDs双氯芬酸对炎症消退的影响。
我们通过将数据映射到“炎症消退图谱”，随后进行计算机模拟和网络分析，推进了先前的研究。我们发现，与双氯芬酸相比，Tr14主要作用于急性炎症的后期（消退期间），双氯芬酸在损伤后立即抑制急性炎症。
我们的结果为多成分药物的网络药理学如何支持炎症性疾病中的炎症消退提供了新的见解。
