Fengyin Decoction (FYD) is a traditional Chinese medicine for the treatment of epilepsy and wind paralysis. However, the potential antiepileptic active component in rhubarb (which is the most effective Chinese medicine in FYD) has not been defined. In this study, we analyzed and predicted the potential quality marker (Q-marker) of rhubarb in FYD based on fingerprint and network pharmacology. The fingerprints of FYD and rhubarb were established to analyze the transmission law of active components. Ultra-high performance liquid chromatography (UPLC) was used to study quantitatively the active components obtained by different extraction methods of FYD. Combined with network pharmacological analysis, a “components-targets-pathways” network was constructed to predict the potential Q-marker. Eight peaks were identified by FYD fingerprint: aloe-emodin, rhein, emodin, chrysophanol, physcion, cinnamaldehyde, 6-gingerol, and glycyrrhizic acid ammonium salt. The determination of the 8 active components in FYD with different extraction methods suggested that rhubarb anthraquinone may be a potential antiepileptic active component. Twelve core components, 19 targets, and 21 pathways of rhubarb were screened by network pharmacology, which further demonstrated that rhubarb played a role mainly through these components, targets, and pathways. We preliminarily predicted that compounds such as rhubarb anthraquinones were a potential Q-marker. The UPLC fingerprint and the content determination method of the 8 components established in this study were effective and feasible. The findings in this study may provide a reference for further study of quality control of FYD and lay a theoretical foundation for the study of its action mechanism. In addition, our study may provide a novel idea for the study of the Q-marker of other classical compound traditional Chinese medicines.

风印汤剂（FYD）是一种治疗癫痫和风瘫的中药。然而，尚未确定大黄（这是 FYD 中最有效的中药）中潜在的抗癫痫活性成分。在本研究中，我们基于指纹图谱和网络药理学对 FYD 中大黄的潜在质量标志物（Q-marker）进行了分析和预测。建立FYD和大黄指纹图谱，分析活性成分的传递规律。采用超高效液相色谱法(UPLC)对不同提取方法的FYD得到的活性成分进行定量研究。结合网络药理分析，构建了“成分-靶点-通路”网络来预测潜在的Q-marker。FYD指纹识别8个峰：芦荟大黄素、大黄酸、大黄素、大黄酚、Physcion、肉桂醛、6-姜酚和甘草酸铵盐。不同提取方法对FYD中8种活性成分的测定表明大黄蒽醌可能是一种潜在的抗癫痫活性成分。通过网络药理学筛选出大黄的12个核心成分、19个靶点和21条通路，进一步证明大黄主要通过这些成分、靶点和通路发挥作用。我们初步预测大黄蒽醌等化合物是潜在的Q-marker。本研究建立的8种成分的UPLC指纹图谱和含量测定方法有效可行。本研究结果可为进一步研究FYD的质量控制提供参考，为其作用机制的研究奠定理论基础。此外，我们的研究可能为其他经典复方中药的Q-marker研究提供新思路。