Preeclampsia remains a leading cause of maternal and perinatal morbidity worldwide, with no effective treatments. Emerging evidence suggests that bioactive compounds derived from plants and plant compounds (used as traditonal Japanese medicine) offer therapeutic potential through anti-inflammatory, antioxidant, and vasomodulatory actions. In this study, we investigated extracts from Cinnamomum cassia and Zingiber officinale, alongside key phytochemicals including cinnamaldehyde, trans-cinnamic acid, and allyl isothiocyanate. These compounds were evaluated for their ability to modulate disease-relevant pathways highly implicated in preeclampsia pathogenesis. By bridging traditional botanical sources with mechanistic screening, this project explores the therapeutic potential of selected fundamental plant-derived compounds for intervention.
Primary human cytotrophoblast cells and placental villous explants were isolated from term uncomplicated pregnancies (delivered via elective caesarean section) and treated for 24 hours with a concentration range of 0.15–1.25 mg/mL for plant extracts (C. cassia, Z. officinale) and 10–100 µM for individual phytochemicals. Conditioned media and RNA were collected for analysis of angiogenic markers. Both C. cassia and Z. officinale extracts significantly reduced secretion of the anti-angiogenic factor sFlt-1 and increased production of the pro-angiogenic molecule PlGF. In parallel, expression of the pathogenic splice variant sFlt-1-e15a was markedly decreased. These changes were consistent across both isolated individual cytotrophoblast and whole tissue villous explants. In contrast, the individual phytochemicals (cinnamaldehyde, trans-cinnamic acid, allyl isothiocyanate) had no significant effect on angiogenic mRNA expression or secretion at any concentration tested. Ongoing studies are examining the effects of these compounds on pro-inflammatory cytokines and key signalling pathways to further elucidate their potential mechanism of action.
These findings support the potential of whole plant extracts, rather than isolated components, to restore angiogenic balance in the placenta. This work contributes to the growing field of pregnancy-safe therapeutics derived from natural products and highlights the promise of plant-based interventions for preeclampsia.