Lycopodii herba (SJC), a traditional Chinese medicine, has the effect of dispelling wind and eliminating dampness (a therapeutic principle and method of traditional Chinese medicine for rheumatoid arthritis), relaxing tendon and activating collaterals. However, the major effective components and its therapeutic mechanism were unclear. In this study, different SJC samples with slightly different compositions were prepared by extracting with different concentrations of ethanol. Then, the therapeutic effects on rheumatoid arthritis (RA) of different SJC samples were evaluated. Finally, the spectrum–effect relationship between UPLC-Q-TOF/MS fingerprints and the effect of RA was explored to screen the effective components. Western blotting was used to study the potential mechanism. The volume of hind paw and the level of RF, TNF-α, and IL-1β were lower after administrating with different SJC samples, compared with the model group. Histopathological findings also confirmed that SJC could relieve the symptoms of RA. Combined with identification of the components in plasm from SJC, lycojaponicumin C, des-N-methyl-α-obscurine, 8β-acetoxy-12β-hydroxy-lycopodine or 8β-acetoxy-11α-hydroxy-lycopodine or 8β-hydroxy-11α-acetoxylycopodine were considered to be the major effective components. The mechanism may be related to AChE/NF-κB signaling pathway. This work provides a general method to screen the potential effective components of herb medicines and would be benefit to understand the mechanism of SJC for the treatment of RA.

石松（SJC）是一种中药，具有祛风除湿（治疗类风湿性关节炎的中医治疗原理和方法）、舒筋活络的功效。然而，主要有效成分及其治疗机制尚不清楚。在本研究中，通过用不同浓度的乙醇萃取制备了具有略微不同成分的不同 SJC 样品。然后，评估不同 SJC 样品对类风湿性关节炎 (RA) 的治疗效果。最后，探索UPLC-Q-TOF/MS指纹图谱与RA效应之间的谱效关系，筛选有效成分。Western印迹用于研究潜在机制。后爪体积和RF、TNF-α水平、与模型组相比，给予不同 SJC 样品后，IL-1β 和 IL-1β 较低。组织病理学发现也证实 SJC 可以缓解 RA 的症状。结合 SJC、lycojaponicumin C、des-N-甲基-α-obscurine、8β-乙酰氧基-12β-羟基-番茄红素或8β-乙酰氧基-11α-羟基-番茄红素或8β-羟基-11α-乙酰氧基番茄红素被认为是主要有效成分。该机制可能与AChE/NF-κB信号通路有关。这项工作提供了一种筛选草药潜在有效成分的通用方法，将有助于了解 SJC 治疗 RA 的机制。