Elucidating the anti-arthritic potential of Crinum asiaticum L. through the TNF signalling pathway: an integrated computational pharmacology, in-vitro and in-vivo approach.

Abstract

Crinum asiaticum L. has been traditionally used for a long time to treat pain, inflammation, rheumatoid arthritis and other inflammatory disorders. However, the anti-arthritic activity and molecular mechanisms of these effects are not well characterised despite its extensive ethnomedicinal use. The present study investigated the anti-arthritic potential of the methanol extract of C. asiaticum (MECA) using an integrated in-silico, in-vitro and in-vivo approach. The phytochemical profile of MECA was characterized by HRLC-QToF-MS analysis, which tentatively identified 23 phytoconstituents. Network pharmacology identified 69 overlapping targets between MECA associated proteins and rheumatoid arthritis-related genes, while GO and KEGG enrichment analyses highlighted several inflammation related pathways among which the TNF signalling pathway emerged as a prominent enriched pathway associated with the anti-arthritic effects of MECA. Molecular docking supported interactions between selected phytoconstituents and inflammatory targets, while molecular dynamics simulation further supported the stability of the Narciclasine-COX-2 complex. In IL-1β-stimulated SW982 human synovial cells, MECA significantly reduced the production of TNF-α, IL-1β, IL-6, PGE₂, nitric oxide and downregulated the expression of AKT1, COX-2 and IL-6. In the Complete Freund's Adjuvant induced arthritis rat model MECA attenuated paw inflammation and arthritic severity, improved biochemical and inflammatory parameters and protected joint architecture, as confirmed by radiographic and histopathological analyses. Collectively, these findings support the anti-arthritic activity of MECA and indicate that TNF-associated signalling may contribute to its observed anti-inflammatory effects. This study provides scientific evidence supporting the traditional use of C. asiaticum and highlights its potential as a complementary therapeutic candidate for the management of rheumatoid arthritis.