Electroacupuncture at LI11 and SP10 is associated with alleviation of acute urticaria-like reactions in passive cutaneous anaphylaxis: an exploratory analysis of complement-related proteins and multiscale omics.

Background: The lifetime prevalence of acute urticaria is approximately 20%. Although electroacupuncture (EA) has been investigated as an adjunctive treatment for urticaria, the molecular mechanisms underlying these effects remain elusive. Passive cutaneous anaphylaxis (PCA) serves as an experimental model of localized acute IgE-mediated hypersensitivity in the skin, and it recapitulates the key phenotypic characteristics of acute urticaria. In this study, we leverage an ovalbumin (OVA)-induced PCA model to characterize molecular alterations in the skin and serum following EA intervention at LI11 and SP10 using integrative proteomic and metabolomic analyses. Methods: An acute urticaria-like model was established via OVA-induced PCA. Rats were treated at the relevant acupoints for 5 consecutive days, during which the blue wheal areas and scratching frequencies were recorded. Immunoassays (ELISA and immunohistochemistry) and histological staining (H&E and toluidine blue) were used to assess cutaneous pathological alterations, vascular permeability, and inflammatory status. Proteomic and metabolomic analyses were conducted on skin and serum samples from three experimental groups to identify differentially expressed proteins and metabolites. An integrative analysis of the omics data was then conducted to explore potential molecular indicators associated with this intervention at both the protein and metabolite levels. Results: In the acute PCA model, the treatment was concurrent with reduced wheal areas, decreased scratching frequencies, and diminished cutaneous vascular permeabilities. These results suggested attenuated acute inflammatory responses. Multi-omics profiling revealed alterations in the lipid and amino acid metabolic pathways linked to this intervention. The western blot and ELISA results indicated that this intervention coincided with the decreased expression of C3a/C5a and their receptors (C3aR/C5aR) in skin tissues, as well as reduced serum levels of inflammatory mediators (IL-6, TNF-α, and 5-HT). Conclusions: The results of our study indicated that in the OVA-induced PCA model, this intervention was associated with decreased expression of components of the C3a/C5a-C3aR/C5aR axis and alterations in metabolic profiles. These exploratory findings may inform future mechanistic studies of complement and metabolism associations in this acute model.