Glycoside fraction from pear seed functionally antagonizes sFLT-1 and restores angiogenic signaling in preeclampsia
10 affiliations
- 1Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB Canada
- 2Department of Biochemistry, Imo State University, Owerri, Nigeria
- 3School of Chemistry, Monash University, Clayton, VIC Australia
- 4Department of Science Laboratory Technology, Imo State Polytechnic, Omuma, Nigeria
- 5Department of Life Sciences, Imperial College London, London, UK
- 6Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB Canada
- 7Department of Biology, St. Mary’s University, Halifax, NS Canada
- 8Department of Biochemistry, Federal University of Lafia, Lafia, Nigeria
- 9Department of Nutrition, Imo State University, Owerri, Nigeria
- 10Department of Medical Biochemistry, Imo State University, Owerri, Nigeria
Abstract
Preeclampsia is characterized by endothelial dysfunction and angiogenic imbalance driven, in part, by excess soluble fms-like tyrosine kinase-1 (sFLT-1). Building on previous findings demonstrating vascular modulatory effects of cardiac and quercetin glycosides from Dacryodes edulis seeds during L-NAME-induced vascular perturbation, we investigated whether pear seed glycosides (PSG) modulate sFLT-1-mediated endothelial injury in preeclampsia. Endothelial, preclinical, biophysical, pharmacodynamic, and exploratory clinical approaches were integrated to evaluate PSG activity. TGFβ-stimulated HUVECs, an L-NAME-induced rat model of preeclampsia, orthogonal binding assays (SPR/BLI and MST), ligand competition assays, and a multicenter double-blind phase 1-2a exploratory clinical trial were employed. PSG reduced endothelial migration and suppressed αSMA, TNFα, and fibronectin expression in stimulated HUVECs. In preeclamptic rats, PSG attenuated systolic and diastolic blood pressure elevation, reduced inflammatory and cardiovascular injury markers, restored VEGF and placental growth factor (PlGF), and reduced circulating sFLT-1 and the sFLT-1/PlGF ratio. Bioactivity-guided fractionation identified glycosides as the principal active fraction and improved mean birth weight from 2.7 g in untreated preeclamptic dams to 3.5 g, approaching normotensive controls (3.7 g). Orthogonal SPR/BLI and MST assays demonstrated concentration-dependent PSG-sFLT-1 interactions, while competitive ELISA and BLI assays showed inhibition of sFLT-1-mediated sequestration of VEGF and PlGF. PSG additionally restored VEGFR2/KDR, AKT, and ERK signaling in sFLT-1-exposed endothelial cells. In the exploratory clinical trial, 83 participants were randomized following screening of 125 women, with approximately 80% completing follow-up. PSG administration alongside standard care did not reveal major treatment-emergent safety concerns. These findings support further investigation of PSG as a candidate adjunctive strategy targeting angiogenic dysfunction in preeclampsia.
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BibTeX
@article{amadi2026glycoside,
title = {{Glycoside fraction from pear seed functionally antagonizes sFLT-1 and restores angiogenic signaling in preeclampsia}},
author = {Peter U. Amadi and Justice O. Osuoha and Atieme J. Ogbolosingha and Govind S. Gill and Suha J. Jarad and Prince C. Odika and Esienanwan E. Efiong and Sayem A. Ahmed and Emmanuel N. Agomuo and Queendarlyn Agbagwara and Chiamaka W. Amadi and Joy A. Amadi and Celestine N. Ekweogu and Hong-mei Gu and Da-wei Zhang},
journal = {Hypertension Research},
year = {2026},
month = sep,
doi = {10.1038/s41440-026-02770-x},
url = {https://doi.org/10.1038/s41440-026-02770-x},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Glycoside fraction from pear seed functionally antagonizes sFLT-1 and restores angiogenic signaling in preeclampsia
AU - Peter U. Amadi
AU - Justice O. Osuoha
AU - Atieme J. Ogbolosingha
AU - Govind S. Gill
AU - Suha J. Jarad
AU - Prince C. Odika
AU - Esienanwan E. Efiong
AU - Sayem A. Ahmed
AU - Emmanuel N. Agomuo
AU - Queendarlyn Agbagwara
AU - Chiamaka W. Amadi
AU - Joy A. Amadi
AU - Celestine N. Ekweogu
AU - Hong-mei Gu
AU - Da-wei Zhang
PY - 2026
DA - 2026/09/01
JO - Hypertension Research
DO - 10.1038/s41440-026-02770-x
UR - https://doi.org/10.1038/s41440-026-02770-x
AB - Preeclampsia is characterized by endothelial dysfunction and angiogenic imbalance driven, in part, by excess soluble fms-like tyrosine kinase-1 (sFLT-1). Building on previous findings demonstrating vascular modulatory effects of cardiac and quercetin glycosides from Dacryodes edulis seeds during L-NAME-induced vascular perturbation, we investigated whether pear seed glycosides (PSG) modulate sFLT-1-mediated endothelial injury in preeclampsia. Endothelial, preclinical, biophysical, pharmacodynamic, and exploratory clinical approaches were integrated to evaluate PSG activity. TGFβ-stimulated HUVECs, an L-NAME-induced rat model of preeclampsia, orthogonal binding assays (SPR/BLI and MST), ligand competition assays, and a multicenter double-blind phase 1-2a exploratory clinical trial were employed. PSG reduced endothelial migration and suppressed αSMA, TNFα, and fibronectin expression in stimulated HUVECs. In preeclamptic rats, PSG attenuated systolic and diastolic blood pressure elevation, reduced inflammatory and cardiovascular injury markers, restored VEGF and placental growth factor (PlGF), and reduced circulating sFLT-1 and the sFLT-1/PlGF ratio. Bioactivity-guided fractionation identified glycosides as the principal active fraction and improved mean birth weight from 2.7 g in untreated preeclamptic dams to 3.5 g, approaching normotensive controls (3.7 g). Orthogonal SPR/BLI and MST assays demonstrated concentration-dependent PSG-sFLT-1 interactions, while competitive ELISA and BLI assays showed inhibition of sFLT-1-mediated sequestration of VEGF and PlGF. PSG additionally restored VEGFR2/KDR, AKT, and ERK signaling in sFLT-1-exposed endothelial cells. In the exploratory clinical trial, 83 participants were randomized following screening of 125 women, with approximately 80% completing follow-up. PSG administration alongside standard care did not reveal major treatment-emergent safety concerns. These findings support further investigation of PSG as a candidate adjunctive strategy targeting angiogenic dysfunction in preeclampsia.
SN - 0916-9636
SN - 1348-4214
ER -