Water Extract of Senecio scandens Buch.-Ham. Ameliorates Allergic Contact Dermatitis by Targeting MrgprB2 and Restoring Sustained Potassium Currents in Dorsal Root Ganglion Neurons

<title>Abstract</title> <p> Background Allergic contact dermatitis (ACD) is a common type IV hypersensitivity skin disorder characterized by recurrent inflammatory lesions and persistent pruritus. Although glucocorticoids are first-line treatments, their long-term use is limited by adverse effects. Mas-related G protein-coupled receptor B2 (MrgprB2) is a key regulator of allergic pruritus. Water extract of <italic>S. scandens</italic> (WSS) has anti-inflammatory and anti-allergic properties; however, its effects on neuronal excitability and its associations with the gut microbiota and host metabolism remain unclear. Purpose This study investigated the therapeutic mechanisms of WSS in ACD, focusing on MrgprB2-associated changes in dorsal root ganglion (DRG) excitability and potential contributions of the gut microbiota and serum metabolome. Methods Oxazolone-induced ACD models were established in C57BL/6J and MrgprB2 ^−/− mice. Clinical scoring, 16S rRNA gene sequencing of the gut microbiota, untargeted serum metabolomics, whole-cell patch-clamp recordings, and enzyme-linked immunosorbent assays were used to assess treatment effects and potential mechanisms. Results WSS significantly reduced skin lesions and pruritus in C57BL/6J ACD mice, with effects comparable to those of hydrocortisone; these effects were not detected in MrgprB2 ^−/− mice. In C57BL/6J mice, WSS altered gut microbial composition, partially restored the serum metabolic profile, and reduced cutaneous pro-inflammatory and pruritogenic mediators. Electrophysiological recordings showed that WSS reduced DRG neuronal hyperexcitability and restored sustained voltage-gated potassium currents. These changes were attenuated or absent in MrgprB2 ^−/− mice, whereas sodium currents were not significantly affected. Conclusion WSS ameliorated ACD in C57BL/6J mice and was associated with restoration of sustained potassium currents in DRG neurons. The loss of efficacy in MrgprB2 ^−/− mice suggests an essential role for MrgprB2, while the microbiome and metabolomic findings identify additional pathways for future mechanistic investigation. </p>