Physalis angulata leaf extract ameliorates L-N G-nitroarginine methyl ester (L-NAME)-induced preeclampsia symptoms in rats through improved endothelial progenitor cells and endothelial cells due to reduced antiangiogenic factor and oxidative stress

• Main Authors: Nugrahenny, Dian, Rudijanto, Achmad, Permatasari, Nur, Wiyasa, I Wayan Arsana, Widodo, Mohammad Aris, Mintaroem, Karyono, Widjajanto, Edi, Mustofa, Mustofa
• Format: Article PeerReviewed
• Language: English
• Published: F1000 Research Ltd 2022
• Subjects: Cancer Diagnosis; Obstetrics and Gynaecology
• Online Access: https://repository.ugm.ac.id/284038/1/2Add_Dian%20Nugrahenny.pdf; https://repository.ugm.ac.id/284038/; https://f1000research.com/articles/11-780
• Institution: Universitas Gadjah Mada

Background: This study aimed to determine the ameliorative effects of Physalis angulata leaf extract on L-NG-nitroarginine methyl ester (L-NAME)-induced preeclampsia symptoms in rats. Methods: Phytochemical analysis of the extract was performed with liquid chromatography-high resolution mass spectrometry (LC-HRMS). Pregnant Wistar rats were randomly divided into five groups (n=6). Preeclampsia rats were injected with L-NAME on gestation days 9 to 18 (G9–G18), while sham rats were injected with the same vehicle volume. Three groups of preeclampsia rats were orally supplemented with the extract at doses of 500, 1500, and 2500 mg/kg body weight/day on G12–G18. The tail-cuff method measured blood pressures. Spectrophotometry determined urine protein levels. Serum soluble fms-like tyrosine kinase (sFlt)-1 levels were evaluated using an enzyme-linked immunosorbent assay (ELISA). Serum and placental malondialdehyde (MDA) levels, superoxide dismutase (SOD) activities, and nitric oxide (NO) levels were measured by colorimetry. Immunohistochemistry was used to determine tail artery endothelial nitric oxide synthase (eNOS), placental eNOS, and placental hypoxia-inducible factor (HIF)-1α expressions. Circulating angiogenic cells (CACs) and endothelial colony-forming cells (ECFCs) were counted using flow cytometry. Results: L-NAME injection increased blood pressures, 24-h total urine protein level, serum sFlt-1 level, serum and placental MDA levels, percentages of CACs and ECFCs, and placental HIF-1α expression. It also decreased serum and placental SOD activities, serum NO level, tail artery and placental eNOS expressions compared to the sham group. Physalis angulata leaf extract administration lowered blood pressures, urine protein level, sFlt-1 level, MDA levels, percentages of CACs and ECFCs, and placental HIF-1α expression. The extract increased SOD activities, NO level, tail artery and placental eNOS expressions compared to the preeclampsia group. Conclusions: Physalis angulata leaf extract reduces antiangiogenic factor and oxidative stress. It also enhances eNOS/NO signaling. Thus, it improves EPC and endothelial cell function and reverses L-NAME-induced hypertension and proteinuria in preeclampsia rats.