Objective To explore the mechanism of Penyan Pills for the treatment of sequelae of pelvic inflammatory disease (SPID) from the perspective of ferroptosis based on bioinformatics method. Methods (1) A total of 40 rats were selected, therein the phenol mucilage process was used to perform SPID modeling on 30 rats, and rats were randomly assigned to model group, Penyan Pills group, or Western Medicine positive control group (azithromycin group), whereas the remaining 10 rats were selected as sham operation group, and they only received operations of open surgery and abdominal closure without injection of phenol mucilage. After modeling finish, rats in the Penyan Pills group received intragastric administration of 0.27 g/(100 g·d) Penyan Pills, while rats of the azithromycin group received intragastric administration of 4.5 mg/(100 g·d) azithromycin, and the sham operation and the model groups received intragastric administration of equivalent normal saline. After 4⁃week intervention, uterine tissues were obtained to perform naked⁃eye observation and HE staining observation. (2) Data sets related to SPID were retrieved from the GEO database, and differential expression analysis was performed on targets concentrated from the data sets for obtaining targets related to SPID. Through the FerrDb platform, targets related to ferroptosis were collected. Corresponding effect targets of drugs constituted by Penyan Pills were collected through HERB platform. Intersection of the aforementioned targets was obtained for acquiring key targets of Penyan Pills for intervening ferrotopsis in treating SPID. For key targets, protein⁃protein interaction (PPI) network was established and the Gene Oncology (GO) enrichment analysis was performed. Traditional Chinese Medicine⁃components⁃targets network was established by the Cytoscape software, and molecular docking analysis was finally performed on key target proteins and corresponding monomer components of Traditional Chinese Medicine. Results (1) After intervention of Penyan Pills, SPID rats model presented as significantly relieved edema in uterine tissues, a generally normal returned uterine structure, epithelium alignment, no denature⁃shedding observed. (2) A total of 3073 targets related to SPID were obtained, and there were 388 targets related to ferroptosis, 395 effect targets of Penyan Pills. After obtaining intersection, 10 key targets of NOS2, RELA, HNF4A, MAPK1, PTEN, SMAD7, GSK3B, TGFB1, RB1, and SRC were acquired, among which SRC, PTEN, and TGFB1 were key nodes of PPI network. The results of GO enrichment analysis revealed that the biological processes involved in key targets contained negative regulation of protein modification processes, etc. In network of Traditional Chinese Medicine⁃components⁃targets, the most important Traditional Chinese Medicine was licorice, the most crucial key target was MAPK1, and the most crucial key monomer component of Traditional Chinese Medicine was apigenin. The results of molecular docking indicated that apigenin exert the lowest docking energy with MAPK1, and the highest possibility to play a role. Conclusion Penyan Pills can intervene targets related to ferroptosis (RELA, MAPK1, TGFB1, SRC, etc.) for treating SPID, its specific mechanism is related to anti⁃chronic inflammatory responses and tissue fibrosis.

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