Botulinum Toxin A alleviates LL-37-induced rosacea-like inflammation in mice, suppressing inflammatory and neurovascular pathways.

Rosacea is a chronic inflammatory skin disorder characterized by flushing, erythema, papules, pustules, and telangiectasia. Current treatments often fall short in addressing the multifaceted nature of the disease, particularly its inflammatory and neurovascular components. While clinical studies suggest Botulinum neurotoxin A (BoNT/A) efficacy, its precise mechanism of action in rosacea remains largely undefined. This study investigates BoNT/A's role in a preclinical model to elucidate its therapeutic potential against LL-37-induced inflammation.

Researchers utilized an LL-37-induced rosacea mouse model to investigate BoNT/A's effects. Mice were divided into four groups: Control, LL-37 only, LL-37 + BoNT/A, and LL-37 + dexamethasone (positive control). The specific dose and route for BoNT/A were not detailed in the abstract. Primary endpoints included assessment of skin damage, thickness, redness severity, and mast cell infiltration. Molecular analyses involved mRNA level quantification of cytokines (IL-6, TNF-α) and inflammasome components (NLRP3, caspase-1, IL-1β), alongside neurovascular factor expression (CD31, TRPV1, CGRPα, VEGF, chymase 1, tryptase α/β1).

BoNT/A treatment effectively alleviated skin damage, reduced skin thickness, and decreased mast cell infiltration in the rosacea mouse model. It significantly improved redness score severity and redness area. Furthermore, BoNT/A enhanced skin barrier function by suppressing transepidermal water loss and increasing skin hydration. At the molecular level, BoNT/A decreased the mRNA levels of pro-inflammatory cytokines IL-6 and TNF-α. It also downregulated the expression of inflammasome components NLRP3, caspase-1, and IL-1β in the LL-37-injected dorsal skin. BoNT/A additionally prevented LL-37-mediated upregulation of key neurovascular-associated factors, including CD31, TRPV1, CGRPα, VEGF, chymase 1, and tryptase α/β1. These findings collectively demonstrate a broad anti-inflammatory and vascular-modulating effect.

BoNT/A effectively alleviated inflammatory and vascular responses in the rosacea mouse model, highlighting its potential as a promising preventive approach for rosacea.