Pharmacological Mechanisms of CheReCunJin Formula in Ameliorating Sjögren's Syndrome: Suppression of IL-17 Signal-Mediated Inflammatory Cascade.

BACKGROUND

Sjögren's Syndrome (SS) is the second most prevalent autoimmune disease in China without effective therapy. Current evidence indicates safety and effectiveness of CheReCunJin formula (CRCJ) in treating SS. However, the underlying mechanism remains unclear.

METHODS

UPLC-Q-TOF-MS was applied for compound identification. Multiple components, targets and pathways involved in the treatment of SS with CRCJ were predicted by network pharmacology. Molecular docking was used for preliminary validation. NOD mouse, a classic spontaneous SS model, was used to examine the therapeutic effects on SS of CRCJ. The potential mechanism of CRCJ to mitigate SS was investigated by serum untargeted metabolomics. Validation of key pathway and targets was conducted using flow cytometry, ELISA, immunohistochemistry, Masson staining, and Western blot.

RESULTS

373 compounds were identified in CRCJ. Through network pharmacology and molecular docking, 15 main components (eg, luteolin 7-O-β-D-glucoside, rutin, 1,4-dicaffeoylquinic acid, anemarsaponin C), 10 core targets (including HSP90AA1, TNF, MMP9, MAPK1, IL6), and the key pathway for CRCJ treating SS, IL-17 signaling pathway, were screened out. In NOD mice, CRCJ demonstrated the ability to improve salivary flow rate and water intake, reduce submandibular gland (SMG) tissue damage, and diminished the levels of IFN-α, IFN-β, IgG in serum. CRCJ modulated metabolic disorders, differentially regulating 63 metabolites and 6 metabolic pathways. Additional validation showed that CRCJ inhibited the Th17 cell activation, downregulated IL-17 signal transduction, and improved ECM degradation in SMG.

CONCLUSION

CRCJ protected salivary glands in SS by inhibiting IL-17 signal-mediated inflammatory cascade, an effect likely attributable to key bioactive components such as luteolin 7-O-β-D-glucoside, rutin, 1,4-dicaffeoylquinic acid, and anemarrhenasaponin C. This study provides a foundation for the further development and clinical application of CRCJ for the treatment of SS.