Melastoma dodecandrum polysaccharide alleviates urticaria via the gut-skin axis by modulating the gut microbiota and the NGF/TRPV1/p38 MAPK pathway.

BACKGROUND

Urticaria is a recurrent inflammatory skin disorder characterized by mast cell activation, neuroimmune dysregulation, and gut microbiota imbalance. Current therapies are associated with limited efficacy and high relapse rates. Although Melastoma dodecandrum Lour. has traditionally been used to treat pruritic and inflammatory disorders, the therapeutic potential and molecular mechanisms of its primary bioactive constituent, Melastoma dodecandrum polysaccharide (MDP), in urticaria remain unclear.

PURPOSE: To evaluate the therapeutic efficacy of MDP in urticaria and characterize its regulatory effects on the neuroimmune-skin axis and gut microbial profiles.

METHODS

A mouse model of urticaria was established by ovalbumin/aluminum (OVA/Alum) sensitization, and MDP (50, 100, and 200 mg/kg) was administered orally. Cutaneous pathology, vascular hyperpermeability, pruritus behavior, and systemic immune responses were assessed by measuring serum immunoglobulin E (IgE), complement components, and splenic T-cell subsets. The NGF/TRPV1/p38 mitogen-activated protein kinase (MAPK) pathway was examined in vivo and in IgE-activated LAD2 mast cells. Gut microbiota composition and fecal metabolite profiles were analyzed to evaluate systemic restoration.

RESULTS

MDP significantly alleviated skin lesions, reduced blood perfusion, and suppressed scratching behavior in urticaria mice. It inhibited mast cell degranulation and reduced pro-inflammatory mediator production. MDP restored immune homeostasis by rebalancing T-cell subsets. Moreover, MDP reversed gut dysbiosis, increased microbial richness, and normalized the abundance of key beneficial taxa. Mechanistically, MDP markedly downregulated the NGF/TRPV1/p38 MAPK signaling pathway in both skin tissue and mast cells.

CONCLUSION

MDP suppresses mast cell-mediated allergic inflammation and modulates the NGF/TRPV1/p38 MAPK neuroimmune axis, suggesting its potential as a multi-target therapeutic candidate for urticaria.