Identification of epiberberine from <i>Scutellaria baicalensis</i> as a selective TNF-α blocker for rheumatoid arthritis treatment

<i>Scutellaria baicalensis</i> (SB) is used to treat rheumatoid arthritis (RA), but its active compounds and mechanisms are unclear. Tumour necrosis factor-α (TNF-α) is a key factor in RA, and finding small-molecule TNF-α blockers is challenging. This study identified 24 active ingredients in SB and 293 overlapping target genes related to RA. TNF-α and Akt1 were identified as hub genes in RA treatment through protein-protein interaction (PPI) analysis, with TNF and PI3K/Akt signalling pathways as core pathways. Molecular docking and molecular dynamics (MD) simulation showed that epiberberine (EPI) from SB had strong binding affinity to TNF-α. <i>In vitro</i>, EPI reduced TNF-α-induced proliferation and cytokine production in MH7A cells, with minimal effect on apoptosis. Mechanistically, EPI downregulated Akt activation by suppressing TNF-α expression. EPI, the predominant active compound from SB, inhibited MH7A cell activation <i>via</i> the TNF-α/PI3K/Akt pathway, showing potential as a novel therapeutic agent for RA.