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Research Article: Distinct Arnica montana L. extracts modulate human T cell activation in different ways via differential inhibition of NF?B and NFAT pathways

Date Published: 2025-10-15

Abstract:
Arnica montana L. (Arnica) has a long history of use in treating inflammation and soft tissue injury, yet its immunomodulatory mechanisms remain largely unexplored. In this study, we investigated the effects of distinct Arnica extracts - derived from different plant parts (root or whole plant) and manufacturing processes - on primary human T cells. We also compared their effects with those of the pure compounds helenalin and thymol. All extracts inhibited T cell activation and proliferation. This could be traced back to reduced IL-2 responsiveness due to decreased CD25 (IL–2R? chain) expression, accompanied by reduced IL-2 production. Transcriptomic analysis (nCounter) and gene set enrichment revealed that the extracts target key T cell receptor (TCR) signaling pathways. Mechanistically, the hydroethanolic root extract selectively inhibited NF?B DNA binding, while the aqueous fermented extract predominantly suppressed NFAT-dependent gene expression. The hydroethanolic whole plant extract exerted a moderate effect on both pathways. These findings identify Arnica extracts as promising modulators of human TCR signaling and support their potential in regulating T cell-driven inflammatory responses, with implications for muscle healing and chronic inflammatory diseases.

Introduction:
For centuries, Arnica montana L. (Arnica) preparations have been used to treat inflammation and to promote the healing of blunt injuries, such as contusions and bruises ( 1 ). A total of about 150 therapeutically active substances have been identified in the different plant parts of Arnica ( 1 ). Its anti-inflammatory mode of action has been mainly attributed to the contained sesquiterpene lactones (SLs), with helenalin as the most prominent representative ( 2 – 4 ). Nuclear factor ‘kappa-light-chain-enhancer’ of…

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