Abstract / Summary
Background: Preeclampsia (PE) is a hypertensive, high incidence disorder occurring only during pregnancy and has high incidence. The Tianma–Gouteng pair (TGP) is used in traditional Chinese medicine for cardiovascular indications, but its candidate bioactive constituents and relevance to PE remain unclear. Objectives: This study aimed to identify candidate TGP compounds relevant to PE and elucidate their effects in experimental trophoblast models. Methods: Placental transcriptomes and network pharmacology analysis were used as an exploratory discovery stage. Candidate compounds of TGP were then evaluated using ADRA1A-overexpression cells and trophoblast organoids, molecular docking, surface plasmon resonance (SPR), and an L-NAME-induced trophoblast organoid injury model. Results: Placental injury and dysfunction were observed in PE mice. Integrated analyses prioritized α1A-adrenergic receptor (ADRA1A) as a candidate TGP-associated target. Five database-derived compounds of TGP were evaluated experimentally. Isorhynchophylline (SRH) showed direct binding to ADRA1A by SPR (equilibrium KD = 4.67 μM). In trophoblast organoids, 15 μM SRH did not significantly reduce viability and was associated with partial restoration of Ki67 and HLA-G expression after L-NAME injury. Conclusions: The data supported ADRA1A as a prioritized candidate target and SRH as a candidate compound with ADRA1A binding and activity in the experimental models. However, the current study did not establish that the biological effects of SRH depend on ADRA1A or demonstrate clinical efficacy of TGP or SRH in PE.