Network pharmacology and experimental validation to investigate the effects of Fructus Psoraleae on the HPA and HPG axes of young rats
Abstract
To investigate the effects of Fructus Psoraleae (FP) on both the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis in juvenile rats across pre-pubertal and post-pubertal stages, as well as to explore its potential implications for biological mechanical properties, a multidisciplinary approach combining network pharmacological analysis, animal experimentation, and biomechanical assessment was employed. Fructus Psoraleae’s potential pharmacological components and targets were identified via the TCMSP database. A GEO search for “precocious puberty” facilitated differential gene analysis with GEO2R. Protein interactions were examined using String, while DAVID analyzed biological processes. Molecular docking was performed using CB-Dock for validation. The effects of Fructus Psoraleae (FP) on the expression of endocrine-related proteins in the HPA and HPG axes of young rats were assessed via enzyme-linked immunosorbent assay (ELISA). Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the expression levels of relevant genes. Computational analysis revealed that FP contains 11 potential pharmacodynamic components and 19 potential targets associated with precocious puberty-related disorders. Notably, compounds such as isopsoralidin, bavachin, and psoralidin exhibited strong binding affinity to acetylcholinesterase (ACHE) targets. KEGG pathway analysis indicated their involvement in significant biological pathways, including the HIF-1 signaling pathway and AMPK signaling pathway. The ELISA results demonstrated notable differences between the FP group and the control group. During the pre-pubertal phase, the FP group exhibited significantly lower levels of corticotropin-releasing hormone (CRH) compared to the control group (P < 0.05). Conversely, in the post-pubertal stage, the FP group showed elevated levels of gonadotropin-releasing hormone (GnRH) relative to the control group (P < 0.01). From a biomechanical view, variations in hormone concentration may be linked to the regulatory effects of blood flow shear stress on the secretory activity of hypothalamic neurons. Furthermore, qRT-PCR analysis showed that estrogen receptor 1 (ESR1) expression was significantly upregulated in the FP group during the pre-pubertal stage (P < 0.01), while ACHE expression was notably reduced in the FP group during the post-pubertal period (P < 0.001). The findings suggest that Fructus Psoraleae does not exert a significant effect on the gonadal axis during the pre-pubertal phase; however, it may have the potential to activate the gonadal axis during the post-pubertal phase. Biomechanical factors may play a significant role in modulating these effects, offering fresh insights into the mechanism by which Fructus Psoraleae exerts its influence on the endocrine system.
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