Identification and mechanism of skin soothing and barrier-improving components in Broussonetia papyrifera extract

Broussonetia papyrifera is traditionally used in Chinese medicine to treat inflammatory skin disorders. This study screened bioactive fractions from B. papyrifera ethanolic extract with anti-inflammatory and skin barrier-improving effects. A flavonoid-rich fraction (BP-F4) significantly inhibited monocyte chemoattractant protein-1 (MCP-1) and the monocyte activation marker CD86 in an in vitro skin inflammation model (TNF-α-induced co-culture of HaCaT keratinocytes and THP-1 monocytes), while an alkaloid fraction (BP-Alkaloids) promoted ceramide production in HaCaT cells as demonstrated by lipidomics. UPLC-QTOF-MS/MS identified 29 flavonoids in BP-F4 and 18 pyrrolidine alkaloids in BP-Alkaloids. RNA-Seq analysis revealed that BP-F4 suppressed the chemokine signalling pathway (HSA04062), whereas BP-Alkaloids activated the PPAR signalling pathway (HSA03320). These findings validate the therapeutic potential of B. papyrifera and provide a rapid screening workflow for skin-active phytochemicals.