Network pharmacology-based approach uncovers the JAK/STAT signaling mechanism underlying paederia scandens extract treatment of rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is a common autoimmune disease. Paederia scandens (Lour.) Merr is a common folk remedy used in Hainan, China, to dispel the wind and dampness associated with RA. Methods: The active components of Paederia scandens were extracted using network pharmacology. The potential targets of active components were used to determine activated pathways, and the in vitro effects of Paederia scandens extracts were verified in RA fibroblast-like synoviocytes (HFLS-RA). Results: We identified 27 active components using ultra-high-performance liquid chromatography (UHPLC)-quadrupole time-of-flight (QTOF)-mass spectrometry (MS). Among the major target genes with high connectivity, IL-1/3, PI3K, TNF, and JAK2 are known to play key roles in RA development. High-affinity interactions were identified between active compounds in Paederia scandens ex-tract and Janus kinase JAK 2, which are key components of the JAK-signal transducer and activator of transcription (STAT) signaling pathway. In HFLS-RA cells, Paederia scandens extract treatment reduced the mRNA levels of IL-6, IL-1 beta, and IL-17. Paederia scandens extract treatment also significantly inhibited the phosphorylation of JAK 2 and STAT3, regulating cell proliferation. Conclusions: Based on these results, we confirmed that Paederia scandens has potential for application as a therapeutic and preventive food and acts through the modulation and suppression of JAK-STAT pathway activation to control the inflammatory response in RA.