Natural products from traditional medicine inherit bioactivity from their source herbs. However, the pharmacological mechanism of natural products is often unclear and studied insufficiently. Pathway fingerprint similarity based on “drug-target-pathway” heterogeneous network provides new insight into Mechanism of Action (MoA) for natural products compared with reference drugs, which are selected approved drugs with similar bioactivity. Natural products with similar pathway fingerprints may have similar MoA to approved drugs. In our study, XYPI, an andrographolide derivative, had similar anti-inflammatory activity to Glucocorticoids (GCs) and non-steroidal anti-inflammatory drugs (NSAIDs), and GCs and NSAIDs have completely different MoA. Based on similarity evaluation, XYPI has similar pathway fingerprints as NSAIDs, but has similar target profile with GCs. The expression pattern of genes in LPS-activated macrophages after XYPI treatment is similar to that after NSAID but not GC treatment, and this experimental result is consistent with the computational prediction based on pathway fingerprints. These results imply that the pathway fingerprints of drugs have potential for drug similarity evaluation. This study used XYPI as an example to propose a new approach for investigating the pharmacological mechanism of natural products using pathway fingerprint similarity based on a “drug-target-pathway” heterogeneous network.

中文翻译：

---

基于“药物-靶点-通路”异质网络的通路指纹相似性天然产物药理机制研究

来自传统医学的天然产品从其来源草药中继承了生物活性。然而，天然产物的药理机制往往不清楚，研究不足。基于“药物-靶点-通路”异质网络的通路指纹相似性为天然产物与参考药物相比的作用机制（MoA）提供了新的见解，参考药物是选择具有相似生物活性的批准药物。具有相似途径指纹的天然产物可能与批准的药物具有相似的 MoA。在我们的研究中，穿心莲内酯衍生物 XYPI 具有与糖皮质激素 (GCs) 和非甾体抗炎药 (NSAIDs) 相似的抗炎活性，并且 GCs 和 NSAIDs 具有完全不同的 MoA。基于相似性评估，XYPI 具有与 NSAIDs 相似的通路指纹，但与 GC 具有相似的目标配置文件。XYPI处理后LPS活化巨噬细胞中基因的表达模式与NSAID而非GC处理后相似，该实验结果与基于通路指纹的计算预测一致。这些结果意味着药物的通路指纹具有用于药物相似性评价的潜力。本研究以XYPI为例，提出了一种基于“药物-靶点-通路”异质网络的通路指纹相似性研究天然产物药理机制的新方法。该实验结果与基于通路指纹的计算预测一致。这些结果意味着药物的通路指纹具有用于药物相似性评价的潜力。本研究以XYPI为例，提出了一种基于“药物-靶点-通路”异质网络的通路指纹相似性研究天然产物药理机制的新方法。该实验结果与基于通路指纹的计算预测一致。这些结果意味着药物的通路指纹具有用于药物相似性评价的潜力。本研究以XYPI为例，提出了一种基于“药物-靶点-通路”异质网络的通路指纹相似性研究天然产物药理机制的新方法。