Network pharmacology and experimental validation uncover how Shoutai pills improve ovarian function in postpartum depression following a secondary birth.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Maternal fertility may be impacted by postpartum depression (PPD), the most common mental illness during the puerperium. Shoutai pills (STW) are extensively applied to strengthen the kidneys and prevent miscarriage, with potential applications in treating depression and improving reproductive function. However, the underlying mechanisms are yet unclear. AIM OF THE STUDY: This study aims to investigate the mechanisms and curative effects of STW in improving ovarian function in secondary-birth postpartum depression (SBPPD). MATERIALS AND METHODS: Active compounds were screened using TCMSP, literature review, and SwissADME. Swiss TargetPrediction and PharmMapper helped in predicting potential targets, while disease targets were identified using GeneCards, DrugBank, OMIM, and DisGeNET. GO and KEGG enrichment analyses were performed using Metascape, and molecular docking validation was then carried out. For animal experiments, a SBPPD model was established through sleep deprivation (SD) and secondary childbirth. The therapeutic effects and mechanisms were investigated based on: behavioral tests, neurotransmitter and hormone level assays, expression analysis of PI3K-AKT pathway-related genes (Immunohistochemistry, Western blot). RESULTS: Network pharmacology analysis identified 35 active components in STW, with 81 overlapping targets related to PPD. The top-ranked targets included ALB, IL6, TNF, AKT1, IL1B, and ESR1. Based on the findings from KEGG analysis and molecular docking studies, it is highly probable that STW exerts its effects via the PI3K-AKT signaling pathway. In vivo experiments demonstrated that STW effectively ameliorated ovarian and neuronal damage induced by PPD. It alleviated depressive-like behaviors, upregulated the expression of proteins linked to the ERs-PI3K-AKT pathway in the ovaries and hippocampal regions, and restored serum levels of CRH, ACTH, CORT, GnRH, FSH, LH, E2, 5-HT, and DA. CONCLUSIONS: STW applys therapeutic effects on SBPPD mice via multiple targets, and its mechanism may be related to modulating the functions of the HPA and HPO axes, with the ERs-PI3K-AKT pathway being a key player in this process.