Exploring the mechanism of Semen Cuscutae processed with salt solution in improving kidney deficiency miscarriage based on serum pharmacochemistry and network pharmacology

Semen Cuscutae (S) is an effective traditional Chinese medicine (TCM) in clinical practice for tonifying the kidney and calming the fetus. The effects of S on benefiting the kidney, fixing essence and calming the fetus were enhanced after salt processed. However, its bioactive substance and relevant mechanism have not been clearly yet. This study aims to explore the effective components of Semen Cuscutae processed with salt solution (Y) and its potential mechanism on the treatment of kidney deficiency miscarriage (KDM) with multi-components and multi-targets. In this study, serum pharmacochemistry and network pharmacology were used to investigate the active ingredients and molecular mechanism of Y in improving kidney deficiency abortion. A rat model of kidney deficiency miscarriage was established using hydroxyurea combine with mifepristone to assess the effect of S on tonifying the kidney and calming the fetus. The results show that 13 active ingredients derived from Y were identified by serum pharmacochemistry analysis. 92 common targets of active ingredients of Y and diseases were screened by network pharmacology, including 18 key targets (TP53, AKT1, TNF, IL6, VEGFA, CASP3, JUN, EGFR, etc). The KEGG pathway enrichment analysis showed that it was mainly concentrated in PI3K/Akt signaling pathway, and it was speculated that Y may protect pregnancy through PI3K/AKT and other signaling pathways with multi-component, multi-target and multi-pathway action characteristics. Animal pharmacodynamic analysis suggested that Y showed the better effect on the hydroxyurea combine with mifepristone induced abortion compared to the raw products of S. This study laid the foundation to identify the active components and potential mechanisms of Y in improving KDM by combining the in-tegrated methods of serum pharma-cochemistry and network pharmacology.