This study employed an integrated strategy combining ultra performance liquid chromatography-linear trap quadrupole-Orbitrap mass spectrometry （UPLC-LTQ-Orbitrap-MS）， network pharmacology， molecular docking simulations， and in vivo animal experimentation to systematically analyze the active components of Synotissolidaginea （S. solidaginea） and to elucidate its underlying therapeutic mechanism in the treatment of acute eczema. Initially， the UPLC-LTQ-Orbitrap-MS method was utilized to perform a comprehensive chemical profiling of S. solidaginea extract. Based on accurate mass， multistage fragmentation spectra， and cross-validation with literature and reference standards， 59 constituents were unambiguously or tentatively identified. Subsequently， a network pharmacology framework was established to predict the potential pharmacological mechanisms of the identified compounds. Among the characterized constituents， seven bioactive ingredients—namely isorhamnetin， kaempferol， luteolin， quercetin， myricetin， betaine， and rosmarinic acid—were selected as the primary active components based on their relative abundance and favorable oral bioavailability and drug-likeness properties as predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The corresponding potential protein targets of these seven compounds were systematically screened using the TCMSP database and the SwissTargetPrediction tool， resulting in the identification of 192 component-associated targets after the removal of duplicate entries. Concurrently， a comprehensive collection of disease-associated targets was curated for acute eczema. By querying the GeneCards database and the Online Mendelian Inheritance in Man （OMIM） database with the keyword “acute eczema”， a total of 2 214 distinct therapeutic targets relevant to the pathogenesis and progression of the dermatological condition were retrieved. Through the construction of a Venn diagram to map the component-related targets onto the disease-specific target set， a core network comprising 75 overlapping targets was identified as the potential therapeutic intersection through which S. solidaginea exerts its pharmacological effects against acute eczema. To further investigate the functional interactions and biological significance of these 75 intersecting proteins， a protein-protein interaction （PPI） network was constructed using the STRING database （version 12.0） and subsequently visualized and topologically analyzed using Cytoscape 3.10.1 software. Network topological analysis， specifically evaluating the degree centrality， betweenness centrality， and closeness centrality， highlighted SRC proto-oncogene tyrosine-protein kinase and matrix metalloproteinase 9 （MMP9） as the most prominent hub nodes within the network， suggesting their pivotal roles in mediating the therapeutic activity. Furthermore， Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted on the 75 potential targets. The GO enrichment analysis indicated that these targets were predominantly involved in biological processes related to the regulation of inflammatory responses， cellular response to oxidative stress， and positive modulation of cytokine production. The KEGG pathway analysis further revealed that the therapeutic effects of S. solidaginea are likely orchestrated through the modulation of several critical signaling cascades， with the PI3K/Akt signaling pathway being the most significantly enriched pathway. To validate the credibility of these computational predictions at the molecular level， molecular docking simulations were performed to evaluate the binding affinities and interaction modes between the core active flavonoids and the identified hub targets. The docking results demonstrated that isorhamnetin， luteolin， quercetin， kaempferol， and myricetin all exhibited strong and stable binding conformations within the active catalytic pockets of both SRC and MMP9. These compounds were observed to form critical hydrogen bonds and hydrophobic interactions with key amino acid residues， indicating a favorable thermodynamic profile and a high potential for functional inhibition of these key targets in vivo. The final phase of this investigation involved experimental validation using an established murine model of acute eczema. The model was successfully induced on the dorsal skin of KM mice through repeated topical sensitization and challenge with 2，4-dinitrochlorobenzene. Following model establishment， the therapeutic impact of S. solidaginea administration was rigorously assessed at the macroscopic， microscopic， and molecular levels. Macroscopic observation and scoring of clinical symptoms revealed a significant amelioration of erythema， edema， and excoriation in the treatment groups. Histopathological examination of skin tissue sections stained with hematoxylin and eosin （HE） confirmed that S. solidaginea treatment markedly reduced epidermal hyperplasia， spongiosis， and dermal inflammatory cell infiltration. Mechanistically， quantitative analysis via enzyme-linked immunosorbent assay （ELISA） demonstrated that S. solidaginea treatment effectively down-regulated the serum concentrations of the key pro-inflammatory cytokines tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， and interleukin-17 （IL-17）， while concurrently restoring the level of interferon-gamma （IFN-γ）. This modulation of cytokine profiles indicates a beneficial shift toward restoring the T helper type 1 cell/T helper type 2 cell （Th1/Th2） immune balance， which is typically dysregulated in acute eczematous conditions. Most importantly， Western blot analysis of the lesional skin tissue provided direct biochemical evidence that the extract of S. solidaginea significantly inhibited the phosphorylation of phosphatidylinositol 3-kinase （PI3K） and protein kinase B （Akt）， thereby confirming the suppression of the PI3K/Akt signaling pathway in vivo. In conclusion， this methodological approach enables the rapid， effective， and comprehensive characterization of the phytochemical profile of S. solidaginea. Furthermore， this study preliminarily elucidates that the therapeutic mechanism of this medicinal plant in treating acute eczema involves a multi-component and multi-target synergistic action， primarily through the alleviation of the cutaneous inflammatory response and the restoration of immune homeostasis via the inhibition of the PI3K/Akt signaling axis. These findings provide a robust scientific foundation and a valuable reference for the further development， clinical application， and quality control of S. solidaginea.