Research on the Mechanism of Asperosaponin VI for Treating Recurrent Spontaneous Abortion by Bioinformatics Analysis and Experimental Validation

Abstract

Asperosaponin VI (AS6), as the quality marker of Dipsaci Radix, is verified to exert therapeutic effect on alleviating recurrent spontaneous abortion (RSA). However, due to the lack of relevant research, its molecular mechanism is still unclear. We retrieved targets for AS6 and RSA, and then used their overlapped targets for PPI analysis. In addition, we used GO and KEGG enrichment analyses, and molecular docking to investigate the anti-RSA mechanisms of AS6. Furthermore, we conducted in vitro experiments to validate the predictions of network pharmacology. Results showed that a total of 103 AS6-associated targets and 2084 RSA-associated targets, with 49 targets overlapped. GO enrichment analysis showed 845 significant biological processes like decidualization, while KEGG pathway enrichment analysis revealed 76 significant entries including 18 signaling pathways, which were closely linked to PI3K-Akt, HIF-1, TNF, IL-17, and VEGF signaling pathways, etc. Molecular docking findings verified that AS6 had tight link with the key targets including JUN, CASP3, STAT3, SRC, and PTGS2. Notably, in vitro experiments revealed that AS6 treatment could exert lower expressions of JUN, pro-CASP3, CASP3, STAT3, SRC, and PTGS2 in decidual cells compared with progesterone despite the expressions of STAT3, SRC, and PTGS2 with no significant difference, and mifepristone could interfere with the effects. In general, numerous targets and multiple pathways involve during the process of AS6 treatment against RSA. Moreover, our in vitro research first reported that AS6 may regulate the expressions of key targets (JUN, CASP3, STAT3, SRC, and PTGS2) in decidual cells to promote decidualization, thus treating RSA.

Parsing the Q-Markers of Baoyin Jian to Treat Abnormal Uterine Bleeding by High-Throughput Chinmedomics Strategy

“…Saponin components can inhibit vascular smooth muscle proliferation and platelet aggregation. Asperosaponin VI has a progesterone-like effect and promotes decidualization by regulating the expression of key targets (JUN, CASP3, STAT3, SRC, and PTGS2) in decidual cells through the activation of PR expression and the Notch signaling pathway, thereby treating recurrent spontaneous abortion [ 35 , 36 ]. Liquiritin significantly activates the Keap1/Nrf2/HO-1 signaling pathway, thereby inhibiting cell oxidative stress and inflammatory reactions and effectively protecting the endometrium [ 37 ].…”