Decoding Preeclampsia and Obesity: The Role of Immune Responses and Natural Product Interventions

Introduction: Preeclampsia (PE) is a pregnancy-specific disorder with high cerebrocardiovascular risk. Obesity increases PE risk, but current monotherapy remains insufficient. Shared mechanisms and natural product-based interventions for PE regarding obesity are urgently needed. Methods: Mendelian Randomization (MR) was used to investigate the causal relationship between PE and obesity, and datasets from GEO were analyzed. Differential expression, enrichment analysis, PPI network, and machine learning (random forests, SVM) were applied to identify characteristic shared genes, which were validated using external datasets. ROC curves assessed diagnostic efficacy. CIBERSORT analyzed immune infiltration. ITGB5 expression was further evaluated using the HPA database. Natural products targeting characteristic genes were predicted, followed by molecular docking and dynamics analysis. Results: MR confirmed obesity as a causal risk factor for PE. GSE96985 and GSE2508 were core datasets. Sixty-nine common DEGs were enriched in muscle cell cytoskeleton pathways. Twenty-- five characteristic genes were screened; six genes showed significant diagnostic efficacy. Immune infiltration suggested CD8+ T cells as a shared immune cell type. ITGB5 was highlighted. HPA confirmed high expression in the placenta and adipose tissue. Puerarin formed a stable complex with ITGB5 (docking energy: -5.92 kJ/mol), supported by molecular dynamics. Discussion: ITGB5 may link PE and obesity via immune-metabolic crosstalk, with CD8+ T cell dysregulation potentially contributing to inflammation, oxidative stress, and endothelial dysfunction. Puerarin emerges as a promising natural agent. Conclusions: These findings suggest that ITGB5 is a candidate shared gene in PE-obesity comorbidity, and that puerarin is a promising natural agent. Given the bioinformatic nature, these conclusions are hypothesis-generating.