Network Pharmacology Combined with In Vivo/In Vitro Experiments and Multi-Omics Technology to Explore the Therapeutic Effect and Mechanism of Periplaneta americana (L.) Extract PA-011 on Solar Dermatitis

This study investigates the therapeutic potential of Periplaneta americana (L.) extract PA-011 (PA-011) in treating solar dermatitis (SD) by integrating LC-MS/MS component analysis with network pharmacology and both in vitro and in vivo experimental approaches. The chemical composition of PA-011 was first characterized using LC-MS/MS, followed by identification of key therapeutic targets through PPI networks, functional enrichment analysis, and molecular docking. In vitro, a UVB-induced HaCaT cell injury model was employed to assess the protective effects of PA-011 using CCK-8, ELISA, and RT-qPCR assays. In vivo, a SD model in Balb/c mice was established to evaluate therapeutic outcomes via macroscopic observation, histopathological examination, ELISA, transcriptomics, RT-qPCR, immunohistochemistry, and non-targeted metabolomics. Results revealed 144 overlapping targets through network pharmacology, with PPI analysis highlighting TNF, IL-1B, and MMP9 as central inflammatory mediators exhibiting strong binding affinity to PA-011. PA-011 significantly enhanced cell viability and suppressed inflammatory cytokines in vitro. In mice, it accelerated skin recovery, alleviated epidermal hyperplasia, increased collagen deposition, and reduced inflammation. Integrated multi-omics and validation experiments demonstrated that PA-011 exerts its effects by downregulating key targets such as IL-1B, AP-1, and MMPs, thereby modulating critical signaling pathways including IL-17 and NF-KB, and restoring metabolic functions related to protein digestion, ABC transporters, and amino acid biosynthesis. Overall, PA-011 effectively reduces erythema and edema, promotes wound healing, and restores skin barrier integrity through multi-pathway regulation, indicating its promising potential for SD treatment.