Abstract Pre-eclampsia remains a persistent challenge in obstetric care, not simply as a disorder of hypertension and proteinuria, but as a syndrome rooted in disrupted placental perfusion, endothelial instability and a complex interplay of oxidative and immunological stressors – renal involvement often emerging later, yet critically shaping disease severity. Current management strategies are largely supportive, with delivery still representing the only definitive intervention. In this context, attention has shifted towards biologically active compounds with the potential to modulate upstream mechanisms. Propolis ethanol extract, a resinous bee-derived substance rich in flavonoids and phenolic esters such as caffeic acid phenethyl ester, pinocembrin and artepillin C, has been explored experimentally for such effects. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidance, with database searches (PubMed, Scopus, Web of Science, Embase and Cochrane Library) performed through May 2025 without language restriction. Eligible studies included in vivo and in vitro investigations examining propolis or its constituents across pathways relevant to pre-eclampsia pathophysiology, whereas reviews and purely computational studies were excluded. From 1245 identified records, 43 studies met the inclusion criteria, of which 20 were classified as low risk of bias using established methodological appraisal tools. Across heterogeneous experimental models, propolis demonstrated consistent antioxidant and vasculoprotective effects, including modulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) and nuclear factor kappa B signalling, improved nitric oxide bioavailability and context-dependent regulation of angiogenic mediators. Evidence of renal protection was observed in non-gestational injury models, although direct evaluation of pregnancy-specific renal endpoints remains notably limited. No systemic toxicity was reported in the included studies; however, human data in pregnancy are lacking, and hypersensitivity reactions described in other settings warrant caution. Overall, the findings support biological plausibility while emphasising the need for standardised preparations, targeted renal assessment and carefully designed safety studies before clinical translation.
Prabowo et al. (2026) studied this question.