柘树叶提取物 (CLE) 长期以来一直被韩国、中国和日本等亚洲国家用作传统东方药物。这些提取物因其在解决炎症、肿瘤、肥胖和糖尿病方面的治疗功效而闻名，保持了其作为关键民间疗法的地位。鉴于草药与传统药物相结合的趋势不断上升，探索潜在的草药与药物相互作用（HDI）势在必行。然而，目前缺乏评估 CLE 的 HDI 的研究。此外，药草复杂的化学成分在建立其成分与 HDI 之间的因果关系方面存在方法学障碍。为了克服这些挑战，开发了计算机模拟和体外相结合的工作流程，并有效地应用于评估 CLE 的潜在 HDI 以及相关的化学因素。在体外 CYP 抑制测定中，CLE 对 CYP1A2 和 CYP2C8 表现出有效的抑制作用，其中槲皮素、山奈酚及其苷类被确定为主要成分。基于预测工具（ADMETlab2.0 和 pkCSM）的计算机分析确定了 CYP 抑制的关键因素：槲皮素和山奈酚。此外，分子对接 (MD) 分析验证了配体（槲皮素和山奈酚）与蛋白质（CYP1A2 和 CYP2C8）的结合。这些发现表明 CLE 可以抑制 CYP1A2 和 CYP2C8，有助于了解 CLE 安全临床应用的 HDI 潜力。此外，这种方法可以广泛应用于研究各种草药的 HDI，通过考虑与草药制剂中 HDI 潜力相关的化学特征来增强其治疗效果并减少不良反应。Thieme。版权所有。

Cudrania tricuspidata leaf extracts (CLEs) have long been utilized as traditional oriental medicines across Asian countries like Korea, China, and Japan. These extracts are renowned for their therapeutic benefits in addressing inflammation, tumors, obesity, and diabetes, maintaining their status as a pivotal folk remedy. Given the rising trend of combining medicinal herbs with conventional medications, it is imperative to explore the potential herb-drug interactions (HDIs). However, there is a dearth of research on evaluating the HDIs of CLEs. Also, the intricate chemical composition of medicinal herbs presents methodological hurdles in establishing causal relationships between their constituents and HDIs. To overcome these challenges, a combined in silico and in vitro workflow was developed and effectively applied to evaluate the potential HDI of CLEs along with the associated chemical factors. In vitro CYP inhibition assays, CLEs exhibited potent inhibition of CYP1A2 and CYP2C8, with quercetin, kaempferol, and their glycosides identified as the major constituents. In silico analysis based on the prediction tools (ADMETlab2.0 and pkCSM) identified key contributors to CYP inhibition, quercetin and kaempferol. Additionally, molecular docking (MD) analysis validated the binding of ligands (quercetin and kaempferol) to proteins (CYP1A2 and CYP2C8). These findings suggest that CLEs could inhibit CYP1A2 and CYP2C8, aiding in understanding the HDI potential of CLEs for safe clinical application. Furthermore, this approach can be broadly applied to study HDIs of various medicinal herbs, enhancing their therapeutic benefits and reducing adverse reactions by considering chemical profiles relevant to HDI potential in herbal preparations.Thieme. All rights reserved.