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

## TL;DR

This study shows that an extract from the plant Dahlia pinnata can selectively reduce a key inflammation molecule (TNF-α) in immune and lung cells without harming them.

## Contribution

The novel finding is that Dahlia pinnata extract suppresses TNF-α more effectively than dexamethasone by modulating NF-κB and p38 pathways.

## Key findings

- D. pinnata extract selectively suppresses TNF-α in THP-1 and BEAS-2B cells without affecting other cytokines or causing toxicity.
- The extract inhibits TNF-α induction from Pseudomonas aeruginosa infection or LPS stimulation more effectively than dexamethasone.
- Two active fractions of the extract inhibit NF-κB and activate p38 signaling to suppress TNF-α expression.

## Abstract

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