Molecular networking-guided isolation of iridoids from Valeriana officinalis with anti-rheumatoid arthritis potential.

A feature-based molecular networking (FBMN)-guided strategy was applied to the targeted chemical investigation of the roots and rhizomes of Valeriana officinalis. This led to the isolation of sixteen iridoids (1-16), including three new compounds (1-3), along with one new monoterpene (17) and one new amide alkaloid (18). The structures of the new compounds were determined by comprehensive spectroscopic analysis (1D/2D NMR, HR-ESI-MS) in combination with ECD calculations. Compounds 6 and 8 reduced the viability of TNF-α-induced RA-FLS (MH7A) cells. Flow cytometry and Western blot analyses indicated that this effect was associated with the induction of late-stage apoptosis. At a non-cytotoxic concentration (1.563 μM), both compounds inhibited the production of the pro-inflammatory cytokine IL-1β. Further insights from non-targeted proteomics, supported by Western blot analysis, suggested the involvement of the NF-κB signaling pathway. Molecular docking and molecular dynamics simulations further suggested that IKKβ may act as a potential binding target of compound 8. These findings expand the chemical profile of V. officinalis and support the potential relevance of its iridoid constituents in RA-related biological processes.