Effect of Pomegranate (Punica Granatum L.) Extract on Endothelial Dysfunction, Vascular, and Renal Damage in a Rat Model of Preeclampsia

Authors

  • Endang Sri Wahyuni Doctoral Program of Medical Sciences, Faculty of Medicine, Universitas Sebelas Maret, Surakarta 57126, Indonesia
  • Soetrisno Department of Obstetrics and Gynaecology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta 57126, Indonesia
  • Bambang Purwanto Department of Internal Medicine, Faculty of Medicine, Universitas Sebelas Maret, Surakarta 57126, Indonesia
  • Brian Wasita Department of Anatomical Pathology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta 57126, Indonesia
  • Vitri Widyaningsih Department of Public Health, Faculty of Medicine, Universitas Sebelas Maret, Surakarta 57126, Indonesia
  • Risya Cilmiaty Department of Oral Disease, Faculty of Medicine, UNS Hospital, Universitas Sebelas Maret, Surakarta 57126, Indonesia
  • Paramasari Dirgahayu Departement of Parasitology Faculty of Medicine, Universitas Sebelas Maret, Surakarta 57126, Indonesia

DOI:

https://doi.org/10.48048/tis.2026.13261

Keywords:

Preeclampsia, Pomegranate extract, Oxidative stress, Inflammation, Nitric oxide, NF-κB, MDA, KIM-1

Abstract

Preeclampsia is a hypertensive disorder of pregnancy marked by elevated blood pressure, proteinuria, and involvement of multiple maternal organs, posing substantial risks to both mother and fetus. Existing therapeutic approaches mainly focus on symptom control and do not directly address the underlying pathophysiological disturbances. This study investigated the potential protective effects of pomegranate (Punica granatum L.) extract in an L-NAME–induced rat model of preeclampsia. Pregnant Sprague-Dawley rats were allocated into 5 experimental groups: Normal pregnancy control, L-NAME–induced preeclampsia (75 mg/kgBW/day), preeclampsia treated with magnesium sulfate (MgSO₄), preeclampsia treated with pomegranate extract (500 mg/kgBW/day), and combination therapy. Biomarkers of oxidative stress (MDA), inflammatory activation (NF-κB), endothelial function (NO), placental vascular remodeling (spiral artery diameter), renal injury (KIM-1), as well as blood pressure, proteinuria, and fetal weight were evaluated. Administration of pomegranate extract significantly lowered NF-κB levels and enhanced nitric oxide availability compared with untreated preeclamptic rats, suggesting reduced inflammatory signaling and improved endothelial performance. Although MDA values tended to decrease in treated groups, this change did not reach statistical significance. The intervention was also associated with enlargement of spiral artery diameter, reduction in KIM-1 expression, slower progression of hypertension and proteinuria, and improved fetal growth. Combined treatment with magnesium sulfate showed additional benefits in several vascular and renal parameters. Overall, these findings indicate that pomegranate extract may exert broad protective effects in experimental preeclampsia by influencing interconnected inflammatory and endothelial pathways, supporting vascular remodeling and renal preservation. The results highlight its potential as an adjunct therapeutic candidate aimed at improving maternal vascular function and fetal development.

HIGHLIGHTS

  • Pomegranate extract modulates oxidative stress markers in the preeclampsia model.
  • Pomegranate extract attenuates inflammatory activation by reducing NF-κB levels in the preeclampsia rat model.
  • Pomegranate extract increases nitric oxide (NO) bioavailability, indicating improved endothelial function.
  • The intervention improves spiral artery remodeling by increasing spiral artery diameter.
  • Pomegranate extract reduces KIM-1 expression, suggesting renoprotective effects.
  • Treatment moderates the progression of hypertension and proteinuria during gestation.

GRAPHICAL ABSTRACT

Downloads

Download data is not yet available.

References

S Rana, E Lemoine, JP Granger and SA Karumanchi. Preeclampsia: Pathophysiology, challenges, and perspectives. Circulation Research 2019; 124(7), 1094-1112.

P Guerby, A Swiader, N Augé, O Parant, C Vayssière, K Uchida, R Salvayre and A Negre-Salvayre. High glutathionylation of placental endothelial nitric oxide synthase in preeclampsia. Redox Biology 2019; 22, 101126.

WD Pangesti, EPS Sasongko, A Pribadi and D Hilmanto. Evaluation of risk factor screening using the ministry of Health’s scoring system for the incidence of early-onset preeclampsia in primary health service. International Journal of Women’s Health 2025; 17, 4815-4822.

V Dines, S Suvakov, A Kattah, J Vermunt, K Narang, M Jayachandran, CA Hassan, AM Norby and VD Garovic. Preeclampsia and the kidney: Pathophysiology and clinical implications. Comprehensive Physiology 2023; 13(1), 4231-4267.

J Torres-Torres, S Espino-Y-Sosa, R Martinez-Portilla, H Borboa-Olivares, G Estrada-Gutierrez, S Acevedo-Gallegos, E Ruiz-Ramirez, M Velasco-Espin, P Cerda-Flores, A Ramirez-Gonzalez and L Rojas-Zepeda. A narrative review on the pathophysiology of preeclampsia. International Journal of Molecular Sciences 2024; 25(14), 7569.

Y Wang, Y Jia, X Yang, B Liang, H Gao and T Yang. A potential role of Baicalin to inhibit apoptosis and protect against acute liver and kidney injury in rat preeclampsia model. Biomedicine and Pharmacotherapy 2018; 108, 1546-1552.

R Aouache, L Biquard, D Vaiman and F Miralles. Oxidative stress in preeclampsia and placental diseases. International Journal of Molecular Sciences 2018; 19(5), 1496.

D Ambarwati, F Fatmawati, M Nooryanto, S Santoso, SCW Baktiyani and N Nurdiana. Punica granatum fruit extract inhibits the production of pro-inflammatory cytokines and angiogenic factors of HUVEC cells induced by plasma from patients with pre-eclampsia. Clinical Nutrition Experimental 2017; 15, 9-14.

W Yu, W Gao, D Rong, Z Wu and RA Khalil. Molecular determinants of microvascular dysfunction in hypertensive pregnancy and preeclampsia. Microcirculation 2019; 26(4), 12508.

S Chaudhuri, B Banerjee, A Kumar and UK Biswas. Association between serum levels of nitric oxide and hydrogen sulfide in pre-eclampsia. Biochemistry & Analytical Biochemistry 2019; 8(3), 384.

J Yuan, X Wang, Y Xie, Y Wang, L Dong, H Li and T Zhu. Circulating asymmetric dimethylarginine and the risk of preeclampsia: A meta-analysis based on 1338 participants. Oncotarget 2017; 8, 43944-43952.

Andriyanti, Restiningsih, B Rahardjo, M Nooryanto, Sri Winarsih, N Permatasari and A Indriani. Effect of pravastatin on levels of malondealdehyde (MDA) and Endothelin-1 (ET-1) preeclampsia model rats. Malaysian Journal of Medicine and Health Sciences 2023; 19(1), 89-95.

M Ożarowski, TM Karpiński, M Szulc, K Wielgus, R Kujawski, H Wolski and A Seremak-Mrozikiewicz. Plant phenolics and extracts in animal models of preeclampsia and clinical trials: Review of perspectives for novel therapies. Pharmaceuticals 2021; 14(3), 259.

MY Ali, S Jannat and MS Chang. Discovery of potent angiotensin-converting enzyme inhibitors in pomegranate as a treatment for hypertension. Journal of Agricultural and Food Chemistry 2023; 71(30), 11476-11490.

ES Wahyuni, L Firrahmawati, IN Mahmudah, JD Handayani and A Rahmawati. Potensi buah delima (Punica granatum) sebagai terapi adjuvan preeklampsia: A scoping review. Holistik Jurnal Kesehatan 2025; 19(5), 987-995.

I Nasifah, S Soeharto and M Nooryanto. Effects of anti-lipid peroxidation of Punica granatum fruit extract in endothelial cells induced by plasma of severe pre-eclamptic patients. Journal of Ayurveda and Integrative Medicine 2017; 8, 215-217.

LE Hosry, C Bou-Mitri, MB Dargham, MA Jaoudeh, A Farhat, JE Hayek, JMB Mosleh and E Bou-Maroun. Phytochemical composition, biological activities and antioxidant potential of pomegranate fruit, juice and molasses: A review. Food Bioscience 2023; 55, 103034.

MI Kojadinovic, AC Arsic, JD Debeljak-Martacic, AI Konic-Ristic, ND Kardum, TB Popovic and MD Glibetic. Consumption of pomegranate juice decreases blood lipid peroxidation and levels of arachidonic acid in women with metabolic syndrome. Journal of the Science of Food and Agriculture 2017; 97(6), 1798-1804.

Y Wang, M Huang, X Yang, Z Yang, L Li and J Mei. Supplementing punicalagin reduces oxidative stress markers and restores angiogenic balance in a rat model of pregnancy-induced hypertension. The Korean Journal of Physiology & Pharmacology 2018; 22(4), 409-417.

D Wang, C Özen, IM Abu-Reidah, S Chigurupati, JK Patra, JO Horbanczuk, A Jóźwik, NT Tzvetkov, P Uhrin and AG Atanasov. Vasculoprotective effects of pomegranate (Punica granatum L.). Frontiers in Pharmacology 2018; 9, 00544.

Y Zhao and F Zong. Inhibiting USP14 ameliorates inflammatory responses in trophoblast cells by suppressing MAPK/NF‐κB signaling. Immunity Inflammation and Disease 2021; 9(3), 1016-1024.

BA Bakrania, EM George and JP Granger. Animal models of preeclampsia: Investigating pathophysiology and therapeutic targets. American Journal of Obstetrics Gynecology 2022; 226(2), 973-987.

NWP Anggraini, S Sulistyowati, Soetrisno, B Purwanto and P Dirgahayu. Effect of moringa oleifera leaves on the expression of NFκβ, E-selectin, and superoxide dismutase in the placental of preeclamptic mouse model. Tropical Journal of Natural Product Research 2025; 9(4), 1800-1805.

Y Anggraini, S Soetrisno, B Wasita and R Cilmiaty. Effects of olive leaf extract and nifedipine, alone and in combination, on blood pressure, neutrophil gelatinase-associated lipocalin, malondialdehyde, and creatinine levels in an Nω-nitro-L-arginine methyl ester-induced rat model of preeclampsia. Pharmacia 2024; 71, 122471.

NZ Shaban, AA Sleem, MM Abu-Serie, AM Maher and NH Habashy. Regulation of the NF-κB signaling pathway and IL-13 in asthmatic rats by aerosol inhalation of the combined active constituents of Punica granatum juice and peel. Biomedicine & Pharmacotherapy 2022; 155, 113721.

A Haseeb, NM Khan, OS Ashruf and TM Haqqi. A polyphenol‐rich pomegranate fruit extract suppresses NF‐κB and IL‐6 expression by blocking the activation of IKKβ and NIK in primary human chondrocytes. Phytotherapy Research 2017; 31(5), 778-782.

JY Jang, D Kim, E Im and ND Kim. Therapeutic potential of pomegranate extract for women’s reproductive health and breast cancer. Life 2024; 14(10), 1264.

N Maphetu, JO Unuofin, NP Masuku, C Olisah and SL Lebelo. Medicinal uses, pharmacological activities, phytochemistry, and the molecular mechanisms of Punica granatum L. (pomegranate) plant extracts: A review. Biomedicine and Pharmacotherapy 2022; 153, 113256.

Z Yisimayili and Z Chao. A review on phytochemicals, metabolic profiles and pharmacokinetics studies of the different parts (juice, seeds, peel, flowers, leaves and bark) of pomegranate (Punica granatum L.). Food Chemistry 2022; 395, 133600.

Z Yisimayili, R Abdulla, Q Tian, Y Wang, M Chen, Z Sun, Z Li, F Liu, HA Aisa and C Huang. A comprehensive study of pomegranate flowers polyphenols and metabolites in rat biological samples by high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Journal of Chromatography A 2019; 1604, 460472.

K Matsubara, T Higaki, Y Matsubara and A Nawa. Nitric oxide and reactive oxygen species in the pathogenesis of preeclampsia. International Journal of Molecular Sciences 2015; 16(3), 4600-4614.

J Kornacki, P Gutaj, A Kalantarova, R Sibiak, M Jankowski and E Wender-Ozegowska. Endothelial dysfunction in pregnancy complications. Biomedicines 2021; 9(12), 1756.

M Moradnia, N Mohammadkhani, B Azizi, M Mohammadi, S Ebrahimpour, O Tabatabaei-Malazy, S Mirsadeghi and M Ale-Ebrahim. The power of punica granatum: A natural remedy for oxidative stress and inflammation; a narrative review. Journal of Ethnopharmacology 2024; 330, 118243.

J Lo, CC Liu, YS Li, PY Lee, PL Liu, PC Wu, TC Lin, CS Chen, CC Chiu, YH Lai, YC Chang, HE Wu, YR Chen, YK Huang, SP Huang, SC Wang and CY Li. Punicalagin attenuates LPS-induced inflammation and ROS production in microglia by inhibiting the MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation. Journal of Inflammation Research 2022; 15, 5347-5359.

Fitriana, S Sulistyowati, D Indarto, S Soetrisno, I Nurwati and V Widyaningsih. Effect of kopyor coconut water on early-onset preeclampsia-like impairments in rats induced by L-nitro-arginine methyl ester. Pharmacia 2024; 71, 127575.

MH Schoots, SJ Gordijn, SA Scherjon, HV Goor and JL Hillebrands. Oxidative stress in placental pathology. Placenta 2018; 69, 153-161.

H Wang, M Li, P Chen and X Shi. Anti-inflammatory and antioxidant effects of pyrroloquinoline quinone in L-NAME-induced preeclampsia-like rat model. Reproductive Sciences 2022; 29, 578-585.

HR Puneeth and SPS Chandra. A review on potential therapeutic properties of Pomegranate (Punica granatum L.). Plant Science Today 2020; 7(1), 9-16.

Aditiawarman, MP Wardhana, LEP Sari and HT Joewono. The effect of l-arginine on diameter of spiral artery and fetal weight between normal pregnant mice and preeclampsia mouse models. International Journal of Pharmaceutical Research 2020; 12(4), 1413-1417.

CX Shi, QH Qi, J Xu and WW Zhao. Protective effect of magnesium sulfate on cranial nerves in preeclampsia rats through the NF-κB/ICAM-1 pathway. European Review for Medical and Pharmacological Sciences 2020; 24(6), 2785-2794.

W Sun, C Yan, B Frost, X Wang, C Hou, M Zeng, H Gao, Y Kang and J Liu. Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats. Scientific Reports 2016; 6, 34246.

A Radajewska, J Szyller, J Niewiadomska, A Noszczyk-Nowak and I Bil-Lula. Punica granatum L. polyphenolic extract as an antioxidant to prevent kidney injury in metabolic syndrome rats. Oxidative Medicine and Cellular Longevity 2023; 2023, 6144967.

F Fitriana, Soetrisno, S Sulistyowati and D Indarto. Evaluation of placental bed uterine in L-NAME-induced early-onset preeclampsia (EO-PE) like the rat model. Turkish Journal of Obstetrics and Gynecology 2024; 21(3), 180-189.

Z Pánczél, Z Kukor, D Supák, B Kovács, A Kecskeméti, R Czizel, M Djurecz, B Alasztics, KB Csomó, A Hrabák and S Valent. Pravastatin induces NO synthesis by enhancing microsomal arginine uptake in healthy and preeclamptic placentas. BMC Pregnancy Childbirth 2019; 19, 426.

ES Wahyuni, Soetrisno, B Purwanto, B Wasita, V Widyaningsih, R Cilmiaty and P Dirgahayu. Pomegranate extract as a natural therapy for preeclampsia: Enhancing endothelial function, modulating inflammation, and boosting antioxidant activity. Trends in Sciences 2026; 23(5), 12241.

SL Finn-Sell, EC Cottrell, SL Greenwood, MR Dilworth, EJ Cowley, CP Sibley and M Wareing. Pomegranate juice supplementation alters utero-placental vascular function and fetal growth in the eNOS-/- mouse model of fetal growth restriction. Frontiers in Physiology 2018; 9, 1145.

Downloads

Published

2026-05-10

How to Cite

Wahyuni, E. S., Soetrisno, S., Purwanto, B., Wasita, B., Widyaningsih, V., Cilmiaty, R., & Dirgahayu, P. (2026). Effect of Pomegranate (Punica Granatum L.) Extract on Endothelial Dysfunction, Vascular, and Renal Damage in a Rat Model of Preeclampsia. Trends in Sciences, 23(10), 13261. https://doi.org/10.48048/tis.2026.13261

Most read articles by the same author(s)

1 2 > >>