Elsayed Sarah A, Ibrahim Reham S, El Naggar El Moataz Bellah, Hassan Yasmine A, Shawky Eman
Department of Pharmacognosy, Faculty of Pharmacy, Damanhur University, Damanhur, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
Sci Rep. 2025 Sep 1;15(1):32091. doi: 10.1038/s41598-025-13412-6.
Garden cress (Lepidium sativum L.) has been traditionally utilized for the treatment of various diseases and is increasingly consumed as a functional food and alternative medicine in many countries due to its therapeutic potential. Notably, L. sativum is a promising candidate for mitigating rheumatoid arthritis (RA). This study employed a serum pharmacochemistry approach combined with a network pharmacology strategy to identify the active components and elucidate the underlying mechanisms of L. sativum in RA management. An RA rat model was established using Complete Freund's Adjuvant (CFA). Following L. sativum administration, bioactive serum components were identified and quantified as markers of its pharmacological activity. Twenty-six serum metabolites, including 11 prototype compounds and 15 derived metabolites, were identified as key bioactive constituents absorbed at significant concentrations, potentially mediating the anti-RA effects of L. sativum. Among these, fatty acids and their conjugated metabolites emerged as the most relevant. Through network pharmacology, potential target genes and associated pathways were predicted. KEGG pathway analysis highlighted critical RA-related pathways, including arachidonic acid metabolism, modulation of inflammatory regulators in TRP channels, linoleic acid metabolism, and antifolate resistance pathways. Experimental data demonstrated that L. sativum significantly downregulated key inflammatory mediators such as IL-1β, TNF-α, MMP-9, CYP1A2, PLA2G2A, and MAPK8. This integrated study provides insight into the molecular mechanisms and active constituents of L. sativum, serving as a foundational reference for its therapeutic application against RA.
水田芥（Lepidium sativum L.）传统上就被用于治疗各种疾病，由于其治疗潜力，在许多国家越来越多地被作为功能性食品和替代药物食用。值得注意的是，水田芥是缓解类风湿性关节炎（RA）的一个有前景的候选物。本研究采用血清药物化学方法结合网络药理学策略来鉴定水田芥在RA治疗中的活性成分并阐明其潜在机制。使用完全弗氏佐剂（CFA）建立RA大鼠模型。给予水田芥后，鉴定并定量生物活性血清成分作为其药理活性的标志物。26种血清代谢物，包括11种原型化合物和15种衍生代谢物，被鉴定为以显著浓度吸收的关键生物活性成分，可能介导水田芥的抗RA作用。其中，脂肪酸及其共轭代谢物最为相关。通过网络药理学，预测了潜在的靶基因和相关途径。KEGG通路分析突出了关键的RA相关通路，包括花生四烯酸代谢、TRP通道中炎症调节因子的调节、亚油酸代谢和抗叶酸耐药途径。实验数据表明，水田芥显著下调关键炎症介质如IL-1β、TNF-α、MMP-9、CYP1A2、PLA2G2A和MAPK8。这项综合研究深入了解了水田芥的分子机制和活性成分，为其抗RA治疗应用提供了基础参考。
