Epigallocatechin gallate (EGCG) alleviates inflammation and endothelial dysfunction and improves pregnancy outcomes in preeclampsia (PE)-like rats via eNOS/Nrf2/HO-1 pathway

Epigallocatechin gallate (EGCG), a natural antioxidant, has shown protective effect in many diseases. We explore the effect and potential regulatory mechanisms of EGCG in preeclampsia (PE)-like rats. PE was mimicked in pregnant rats. EGCG was orally administered at a dosage of 25(Low, L) or 50 mg/kg (High, H) from gestational day (GD) 6 to 17. The blood pressure signatures, heart rates were monitored. The 24-h proteinuria and serum were analyzed. On GD 18, rats were sacrificed, and pups and placentas were weighed. Kidneys and placentas were analyzed using immunohistochemistry (IHC) and hematoxylin-eosin staining (H&E). Placentas were examined using western blot for sFlt1, eNOS, Nrf2, HO-1, SLC7A11. MDA, GSH, GPx and Fe2+ were measured. EGCG inhibits systolic blood pressure, BUN, CREA, ALT, AST, UA and proteinuria levels in PE-like rats. EGCG enhances the pup weight and crown-rump length and reduces the rate of fetus growth restriction in PE group. Endothelial dysfunction and infiltration of inflammatory cells were found in kidney cortex and placenta tissues in PE group and were inhibited by EGCG treatment. sFlt1 was activated in placentas in PE group and inhibited by EGCG while eNOS/Nrf2/HO-1 were inhibited in PE group and restored by EGCG. MDA and Fe concentrations were elevated in PE group and reduced by EGCG while the GSH level, SLC7A11 and the GPx activity were inhibited in PE group and restored by EGCG. EGCG alleviates inflammation, endothelial dysfunction and placental ferroptosis, improves pregnancy outcomes in PE-like rats via eNOS/Nrf2/HO-1.