Identification of Shared Targets of Ginseng and Angelica sinensis in Premature Ovarian Failure: Network Pharmacology and Mendelian Randomization Analysis.

BACKGROUND: As key medicinal targets, ginseng and Angelica sinensis have demonstrated potential efficacy in the treatment of Premature Ovarian Failure (POF). This study identified the key targets and further explored their potential causal links with POF using Mendelian randomization (MR) analysis. METHOD: This study integrated network pharmacology and transcriptomic data to identify novel POFassociated targets using differential expression analysis, Protein-Protein Interaction (PPI) network construction, machine learning algorithms, and expression validation. Additionally, it performed gene set enrichment analysis (GSEA), immune infiltration analysis, and single-cell RNA sequencing to investigate the potential biological roles of these targets in POF. RESULTS: HSD17B1, MAPK14, and CDC7 were identified as the key targets related to ginseng and Angelica sinensis in POF. HSD17B1 and CDC7 were downregulated, while MAPK14 was upregulated, and these targets were enriched in immune- and metabolism-related pathways. MAPK14 was strongly correlated with γδ T cells (cor = 0.82, P < 0.05). Single-cell analysis identified nine ovarian cell subpopulations. MR analysis indicated that HSD17B1 was associated with an increased risk of female infertility [FINN-b-N14 FEMALEINFERT: odds ratio (OR) = 1.175, 95% confidence interval (CI) = 1.064-1.298; FINN-b-N14 FIANOV: OR = 1.459, 95% CI = 1.154-1.845; P < 0.05]. DISCUSSION: These findings indicate that ginseng and Angelica sinensis might modulate steroidogenesis, immune responses, and granulosa-cell function, with HSD17B1, MAPK14, and CDC7 identified as candidate biomarkers, warranting further mechanistic exploration in POF. CONCLUSION: This study identified three key targets (HSD17B1, MAPK14, and CDC7) associated with ginseng and Angelica sinensis that may be involved in the pathogenesis of POF and may serve as candidate markers for subsequent mechanistic exploration.