Population-Level Burden of Dermatitis and the Effects of Moxibustion and Capsaicin on Pruritus and JAK/STAT Signaling in Atopic Dermatitis: A Multilevel Study.
Yang Yunhong Y, Guo Lihua L, Yang Yunsong Y, Tang Han H et al.
This study comprised two complementary levels of investigation. First, we characterized the global burden, temporal trends, and socioeconomic inequalities of dermatitis as an aggregated disease category. Second, within this broader public-health context, we investigated whether moxibustion and topical capsaicin alleviate pruritus and inflammatory skin damage in a rat model of atopic dermatitis (AD) and explored their potential convergent regulation of the Janus kinase (JAK)/STAT signaling pathway. The study comprised a population-level contextual analysis and a disease-specific experimental investigation. Age-standardized incidence rates (ASIRs) and disability-adjusted life years (DALYs) attributable to each risk factor for dermatitis were extracted and assessed from the Global Burden of Disease (GBD) database. The GBD component was used to characterize the broader public-health burden of dermatitis and was not interpreted as an AD-specific epidemiological analysis. An AD rat model was established using 2,4-dinitrochlorobenzene (DNCB) in an acetone solution. Successfully modeled rats were randomly assigned to untreated model, mometasone furoate cream, moxibustion, or topical capsaicin groups. The standard pharmacological treatment group was included as a therapeutic efficacy benchmark, whereas capsaicin was used as a sensory-neuron-modulating active comparator for the exploratory analysis of downstream molecular convergence. Proteomic analysis was used to identify treatment-associated pathways, and changes in IFN-γ/JAK1/STAT1/STAT3 signaling components were subsequently assessed by western blotting, RT-qPCR, and immunohistochemistry. In addition to skin-lesion severity and scratching behavior, pruritus-related neuroimmune mediators were evaluated. Serum IL-31 concentrations were measured by ELISA. Cutaneous IL-31 and TRPV1 expression was assessed by immunohistochemistry, and substance P immunoreactivity was evaluated by immunofluorescence. The relative mRNA expression of Trpv1, SP(Tac1), and CGRP in lesional skin was measured by RT-qPCR. The global incidence of dermatitis increased, with a higher burden in females. Significant inequalities in incidence and DALYs existed across countries of varying sociodemographic index (SDI) levels. At the experimental level, target intersection analysis identified 302 genes shared by capsaicin, AD, and pruritus, while lesional-skin proteomics identified 257 common differentially expressed proteins. Exploratory proteomic enrichment identified JAK/STAT signaling as the most prominent candidate pathway in the enrichment bubble plot. AD model rats exhibited increased scratching, upregulated pruritus-related mediators (IL-31, TRPV1, substance P, and Trpv1/Tac1/CGRP transcripts), exacerbated skin lesions, histopathological damage, and a pro-inflammatory shift (elevated IL-1, IL-4, IL-6, TNF-α, IFN-γ; reduced IL-10). Mometasone furoate predictably alleviated these AD-like manifestations. Both moxibustion and capsaicin treatments reversed these trends, improving pathology, restoring spleen/thymus indices, and downregulating IFN-γ expression and JAK1/STAT1/STAT3 phosphorylation. Aggregated dermatitis continues to impose a substantial and unevenly distributed global health burden. Within this broader public-health context, the experimental findings indicate that moxibustion and topical capsaicin alleviate pruritus and inflammatory skin damage in rats with AD. These improvements were accompanied by attenuation of IFN-γ/JAK1/STAT1/STAT3-associated signaling, supporting the potential involvement of the JAK/STAT pathway in the observed treatment responses.