Traditional Medicinal Plant Dahlia pinnata Selectively Suppresses TNF-α Expression Through Modulation of NF-κB and p38 Signaling

초록

Tumor necrosis factor-alpha (TNF-alpha) is a central mediator of inflammatory pathology; thus, the selective suppression of TNF-alpha without causing broad immunosuppression remains a critical therapeutic goal. This study investigated the anti-inflammatory potential and underlying mechanisms of Dahlia pinnata (D. pinnata) extract in human monocytes and epithelial cells. We demonstrate that D. pinnata extract selectively suppresses basal TNF-alpha expression in THP-1 monocytes and BEAS-2B bronchial epithelial cells, with minimal impact on IL-1 beta, IL-6, or IL-10 and without inducing cytotoxicity. The extract also potently attenuated TNF-alpha induction triggered by Pseudomonas aeruginosa infection or lipopolysaccharide (LPS) stimulation. Notably, D. pinnata extract exhibited stronger and broader TNF-alpha-suppressive effects than dexamethasone, particularly in monocytes where dexamethasone was ineffective under the tested conditions. Mechanistic analyses revealed that the extract suppresses TNF-alpha expression primarily through the inhibition of NF-kappa B signaling, accompanied by enhanced p38 MAPK activation. Fractionation of the extract identified two active fractions (06 and 07) that robustly suppressed TNF-alpha expression under both basal and stimulated conditions while maintaining low cytotoxicity. These fractions recapitulated the signaling profile of the crude extract by inhibiting NF-kappa B activation and promoting p38 signaling. Collectively, our findings identify D. pinnata as a rich source of bioactive compounds that selectively suppresses TNF-alpha through the coordinated modulation of NF-kappa B and p38 pathways, highlighting its potential as a scaffold for developing targeted anti-inflammatory therapeutics.

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