Quercetin as a promising phytotherapeutic candidate in preeclampsia: a narrative review
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20261310Keywords:
Preeclampsia, Treatment, Management, QuercetinAbstract
Preeclampsia, a pregnancy specific hypertensive disorder, is one of the major cause of maternal and fetal morbidity and mortality globally. It occurs after 20 weeks of gestational period with high blood pressure and proteinuria, primarily caused by abnormal placental development with impaired endothelial function, and widespread inflammation. Current treatment strategies focus on the management of clinical symptoms of this disorder by using pharmaceutical agents like aspirin, Methyldopa, labetalol, hydralazine or nifedipine. But, these drugs cause various adverse effects on pregnancy due to which the researchers have started to explore the potential of several natural bioactive phytoconstituents to discover a safer and healthy alternative. One of these compounds is quercetin, a flavonol that exhibits significant antioxidant, anti-inflammatory, and immune-regulating properties. Preclinical studies have revealed that it helps in maintaining endothelial balance by regulating many inflammatory mediators. Different innovative delivery methods such as nanoparticles and liposomes are being developed to improve its efficacy as a natural therapeutic. The present review will provide insight into the immunology of preeclampsia along with its management by using a multi- targeted and safe natural therapeutic agent i.e. quercetin which in future may be used as an augmented therapy aimed at improving the both maternal and child health.
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References
Shamsi U, Saleem S, Nishter N, Ameen A. Epidemiology and risk factors of preeclampsia: an overview of observational studies. Al Ameen J Med Sci. 2013;6(4):292-300.
Michalczyk M, Celewicz A, Celewicz M, Woźniakowska Gondek P, Rzepka R. The role of inflammation in the pathogenesis of preeclampsia. Mediators Inflamm. 2020;2020:3864941. DOI: https://doi.org/10.1155/2020/3864941
Shandilya V, Sinha N, Rani S. Preeclampsia: prevalence, risk factors, and impact on mother and fetus. Indian J Cardiovasc Dis Women. 2023;8(3):193-9. DOI: https://doi.org/10.25259/IJCDW_32_2023
Harutyunyan A, Armenian H, Petrosyan V. Interbirth interval and history of previous preeclampsia: a case–control study among multiparous women. BMC Pregnancy Childbirth. 2013;13:244. DOI: https://doi.org/10.1186/1471-2393-13-244
Zhang Y, Diao Z, Su L, Sun H, Li R, Cui H, et al. MicroRNA-155 contributes to preeclampsia by down-regulating CYR61. Am J Obstet Gynecol. 2010;202(5):466.e1-e7. DOI: https://doi.org/10.1016/j.ajog.2010.01.057
Janani F, Changaee F. Seasonal variation in the prevalence of preeclampsia. J Family Med Prim Care. 2017;6(4):766-9. DOI: https://doi.org/10.4103/jfmpc.jfmpc_132_17
Peng X, Oluchi-Amaka IC, Kwak-Kim J, Yang X.A comprehensive review of the roles of T-cell immunity in preeclampsia. Front Immunol. 2025;16:1476123. DOI: https://doi.org/10.3389/fimmu.2025.1476123
Shahgheibi S, Rezaie M, Kamangar TM, Zarea S, Yousefi SR. The effect of season on the prevalence of preeclampsia. J Clin Gynecol Obstet. 2016;5(3):81-4. DOI: https://doi.org/10.14740/jcgo408w
Saito S, Shiozaki A, Nakashima A, Sakai M, Sasaki Y. The role of the immune system in preeclampsia. Mol Aspects Med. 2007;28(2):192-209. DOI: https://doi.org/10.1016/j.mam.2007.02.006
Orefice R. Immunology and the immunological response in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2021;76:3-12. DOI: https://doi.org/10.1016/j.bpobgyn.2020.07.013
Tranquilli AL, Dekker G, Magee L, Roberts J, Sibai BM, Steyn W, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP. Pregnancy Hypertens. 2014;4(2):97-104. DOI: https://doi.org/10.1016/j.preghy.2014.02.001
Wiciński M, Malinowski B, Puk O, Socha M, Słupski M. Methyldopa as an inductor of postpartum depression and maternal blues: a review. Biomed Pharmacother. 2020;127:110196. DOI: https://doi.org/10.1016/j.biopha.2020.110196
Xie J, Zhang AH, Sun H, Yan GL, Wang XJ. Recent advances and effective strategies in the discovery and applications of natural products. RSC Adv. 2018;8(2):812-24. DOI: https://doi.org/10.1039/C7RA09475B
Sugulle M, Fiska BS, Jacobsen DP, Fjeldstad HE, Staff AC. Placental senescence and the two-stage model of preeclampsia. Am J Reprod Immunol. 2024;92(1):e13904. DOI: https://doi.org/10.1111/aji.13904
Lesjak M, Beara I, Simin N, Pintać D, Majkić T, Bekvalac K, et al. Antioxidant and anti-inflammatory activities of quercetin and its derivatives. J Funct Foods. 2018;40:68-75. DOI: https://doi.org/10.1016/j.jff.2017.10.047
Li Q, Yin L, Si Y, Zhang C, Meng Y, Yang W. The bioflavonoid quercetin improves pathophysiology in a rat model of preeclampsia. Biomed Pharmacother. 2020;127:110122. DOI: https://doi.org/10.1016/j.biopha.2020.110122
Popiolek Kalisz J, Fornal E. The effects of quercetin supplementation on blood pressure—meta-analysis. Curr Probl Cardiol. 2022;47(11):101350. DOI: https://doi.org/10.1016/j.cpcardiol.2022.101350
Abbas M, Saeed F, Anjum FM, Afzaal M, Tufail T, Bashir MS, et al. Natural polyphenols: an overview. Int J Food Prop. 2017;20(8):1689-99. DOI: https://doi.org/10.1080/10942912.2016.1220393
Mlcek J, Jurikova T, Skrovankova S, Sochor J. Quercetin and its anti-allergic immune response. Molecules. 2016;21(5):623. DOI: https://doi.org/10.3390/molecules21050623
Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules. 2019;24(6):1123. DOI: https://doi.org/10.3390/molecules24061123
Huang H, Liao D, Dong Y, Pu R. Effect of quercetin supplementation on plasma lipid profiles, blood pressure, and glucose levels: a systematic review and meta-analysis. Nutr Rev. 2020;78(8):615-26. DOI: https://doi.org/10.1093/nutrit/nuz071
Comalada M, Camuesco D, Sierra S, Ballester I, Xaus J, Gálvez J, et al. In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-κB pathway. Eur J Immunol. 2005;35(2):584-92. DOI: https://doi.org/10.1002/eji.200425778
Chaouat G, Petitbarat M, Dubanchet S, Rahmati M, Ledée N. Tolerance to the foetal allograft? Am J Reprod Immunol. 2010;63(6):624-36. DOI: https://doi.org/10.1111/j.1600-0897.2010.00832.x
Aneman I, Pienaar D, Suvakov S, Simic TP, Garovic VD, McClements L. Mechanisms of key innate immune cells in early and late onset preeclampsia. Front Immunol. 2020;11:1864. DOI: https://doi.org/10.3389/fimmu.2020.01864
Chaparro A, Monckeberg M, Realini O, Hernández M, Param F, Albers D, et al. Gingival crevicular placental alkaline phosphatase is an early pregnancy biomarker for preeclampsia. Diagnostics. 2021;11(4):661. DOI: https://doi.org/10.3390/diagnostics11040661
Bonney EA. Alternative theories: pregnancy and immune tolerance. J Reprod Immunol. 2017;123:65-71. DOI: https://doi.org/10.1016/j.jri.2017.09.005
Vivier E, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, et al. Innate lymphoid cells: 10 years on. Cell. 2018;174(5):1054-66. DOI: https://doi.org/10.1016/j.cell.2018.07.017
Guerin LR, Moldenhauer LM, Prins JR, Bromfield JJ, Hayball JD, Robertson SA et al. Seminal fluid regulates accumulation of FOXP3+ regulatory T cells in the preimplantation mouse uterus. Biol Reprod. 2011;85(2):397-408. DOI: https://doi.org/10.1095/biolreprod.110.088591
Robertson SA, Care AS, Moldenhauer LM. Regulatory T cells in embryo implantation and the immune response to pregnancy. J Clin Invest. 2018;128(10):4224-35. DOI: https://doi.org/10.1172/JCI122182
Faas MM, de Vos P. Maternal monocytes in pregnancy and preeclampsia in humans and in rats. J Reprod Immunol. 2017;119:91-7. DOI: https://doi.org/10.1016/j.jri.2016.06.009
Abu-Raya B, Michalski C, Sadarangani M, Lavoie PM. Maternal immunological adaptation during normal pregnancy. Front Immunol. 2020;11:575197. DOI: https://doi.org/10.3389/fimmu.2020.575197
Redman CWG, Sargent IL. Placental stress and pre-eclampsia: a revised view. Placenta. 2009;30(A):S38-42. DOI: https://doi.org/10.1016/j.placenta.2008.11.021
Sah A, Naseef PP, Kuruniyan MS, Jain GK, Zakir F, Aggarwal G. A comprehensive study of therapeutic applications of chamomile. Pharmaceuticals (Basel). 2022;15(10):1284. DOI: https://doi.org/10.3390/ph15101284
Yao J, Long H, Zhao J, Zhong G, Li J. Nifedipine inhibits oxidative stress and ameliorates osteoarthritis. Life Sci. 2020;253:117292. DOI: https://doi.org/10.1016/j.lfs.2020.117292
Odigboegwu O, Pan LJ, Chatterjee P. Use of antihypertensive drugs during preeclampsia. Front Cardiovasc Med. 2018;5:50. DOI: https://doi.org/10.3389/fcvm.2018.00050
Rolnik DL, Nicolaides KH, Poon LC. Prevention of preeclampsia with aspirin. Am J Obstet Gynecol. 2022;226(2 Suppl):S1108-19. DOI: https://doi.org/10.1016/j.ajog.2020.08.045
Celec P. Nuclear factor kappa B—molecular biomedicine: the next generation. Biomed Pharmacother. 2004;58(6-7):365-71. DOI: https://doi.org/10.1016/j.biopha.2003.12.015
Atallah A, Lecarpentier E, Goffinet F, Doret-Dion M, Gaucherand P, Tsatsaris V. Aspirin for prevention of preeclampsia. Drugs. 2017;77(17):1819-31. DOI: https://doi.org/10.1007/s40265-017-0823-0
Yang S, Song L, Shi X, Zhao N, Ma Y. Ameliorative effects of preeclampsia by quercetin supplement to aspirin. Biomed Pharmacother. 2019;116:108969.
Ożarowski M, Mikołajczak PŁ, Kujawski R, Wielgus K, Klejewski A, Wolski H, et al. Pharmacological effect of quercetin in hypertension. Evid Based Complement Alternat Med. 2018;2018:7421489. DOI: https://doi.org/10.1155/2018/7421489
Bralewska M, Rybak-Krzyszkowska M, Grzesiak M, Pietrucha T. New ideas for the prevention and treatment of preeclampsia. Int J Mol Sci. 2023;24(15):12100. DOI: https://doi.org/10.3390/ijms241512100
Sánchez M, González-Burgos E, Iglesias I, Lozano R, Gómez-Serranillos MP. Pharmacological activity of Camellia sinensis. Biomolecules. 2020;10(4):603. DOI: https://doi.org/10.3390/biom10040603
Stainer AR, Sasikumar P, Bye AP, Unsworth AJ, Holbrook LM, Tindall M, et al. Metabolites of quercetin possess potent antithrombotic activity. TH Open. 2019;3(3):e244-58. DOI: https://doi.org/10.1055/s-0039-1694028
Widyaningrum SA, Wasita B, Nuhriawangsa AM. Levels of quercetin and antioxidant activity of Patikan Kebo leaves extract. In: Proc 4th Int Conf Soc Determinants Health. 2022;89-93. DOI: https://doi.org/10.5220/0011650500003608
Salvamani S, Gunasekaran B, Shaharuddin NA, Ahmad SA, Shukor MY. Antiartherosclerotic effects of plant flavonoids. Biomed Res Int. 2014;2014:480258. DOI: https://doi.org/10.1155/2014/480258
Sidor A, Gramza-Michałowska A. Elderberry health benefits. J Funct Foods. 2015;18:941-58. DOI: https://doi.org/10.1016/j.jff.2014.07.012
Kashyap P, Kumar S, Riar CS, Baniwal P, Guiné RP, Correia PM, et al. Advances in Moringa oleifera leaves bioactives. Antioxidants (Basel). 2022;11(2):402. DOI: https://doi.org/10.3390/antiox11020402
Michala AS, Pritsa A. Quercetin: biochemical and clinical value. Diseases. 2022;10(3):37. DOI: https://doi.org/10.3390/diseases10030037
Tain YL, Hsu CN. Maternal polyphenols and offspring health. Nutrients. 2024;16(18):3168. DOI: https://doi.org/10.3390/nu16183168
Cao L, Tan C, Meng F, Liu P, Reece EA, Zhao Z. Quercetin reduces neural tube defects. Sci Rep. 2016;6:21491. DOI: https://doi.org/10.1038/srep21491
Bolouki A, Zal F, Mostafavi Pour Z, Bakhtari A. Protective effects of quercetin in diabetic pregnancy. Taiwan J Obstet Gynecol. 2020;59(6):927-34. DOI: https://doi.org/10.1016/j.tjog.2020.09.038
David AVA, Arulmoli R, Parasuraman S. Biological importance of quercetin. Pharmacogn Rev. 2016;10(20):84-9. DOI: https://doi.org/10.4103/0973-7847.194044
Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, et al. Quercetin, inflammation and immunity. Nutrients. 2016;8(3):167. DOI: https://doi.org/10.3390/nu8030167
Hashemzaei M, Delarami Far A, Yari A, Heravi RE, Tabrizian K, Taghdisi SM, et al. Anticancer effects of quercetin. Oncol Rep. 2017;38(2):819-28. DOI: https://doi.org/10.3892/or.2017.5766
Costa PCT da, de Souza EL, Lacerda DC, Cruz Neto JP, Sales LC, Silva Luis CC, et al. Quercetin in cardiometabolic diseases in pregnancy. Foods. 2022;11(18):2772. DOI: https://doi.org/10.3390/foods11182772
Zhang W, Zheng Y, Yan F, Dong M, Ren Y. Research progress of quercetin in cardiovascular disease. Front Cardiovasc Med. 2023;10:1203713. DOI: https://doi.org/10.3389/fcvm.2023.1203713
Ansari P, Choudhury ST, Seidel V, Rahman AB, Aziz MA, Richi AE, et al. Therapeutic potential of quercetin in type 2 diabetes mellitus. Life. 2022;12(8):1146. DOI: https://doi.org/10.3390/life12081146
Meseret AA, Wondimagegne ZT. Predictive factors of undernutrition in diabetes. J Nutr Sci. 2025;14:e32. DOI: https://doi.org/10.1017/jns.2025.21
Jagru P, Natarajan SB, Shanmugam N, Perera T, Parameswaran SK. Phytochemicals in diabetic neuropathy. Int J Food Drug Cosmet. 2025;1(2):16-38.
Yang S, Song L, Shi X, Zhao N, Ma Y. Quercetin supplement to aspirin in preeclampsia. Biomed Pharmacother. 2019;116:108969. DOI: https://doi.org/10.1016/j.biopha.2019.108969
Vangrieken P, Al Nasiry S, Bast A, Leermakers PA, Tulen CB, Janssen GM, et al. Hypoxia-induced mitochondrial abnormalities in placenta. PLoS One. 2021;16(1):e0245155. DOI: https://doi.org/10.1371/journal.pone.0245155
Yang S, Zhang J, Chen D, Ding J, Zhang Y, Song L. Quercetin attenuates L-NAME-induced preeclampsia-like impairments. Drugs R D. 2022;22(4):271-9. DOI: https://doi.org/10.1007/s40268-022-00402-6
Yoshida K, Kusama K, Shinohara G, Sato S, Yoshie M, Tamura K . Quercetin stimulates trophoblast fusion. Sci Rep. 2024;14(1):287. DOI: https://doi.org/10.1038/s41598-023-50712-1
Ding J, Yang S, Chen D, Shi X, Zhang Y, Song L, et al. Protective effects of aspirin with quercetin. Physiol Res. 2024;73(1):37-45. DOI: https://doi.org/10.33549/physiolres.935196
Vangrieken P, Al Nasiry S, Remels AHV, Schiffers PM, Janssen E, Nass S, et al. Placental methylglyoxal in preeclampsia. Hypertension. 2024;81(7):1537-49. DOI: https://doi.org/10.1161/HYPERTENSIONAHA.123.22633
Shi M, Sun L, Wei J, Shen Y, Wang J, Zhang P, et al. Quercetin alleviates endothelial dysfunction. Commun Biol. 2025;8(1):90. DOI: https://doi.org/10.1038/s42003-025-07547-5
Nguyen PY, Sanderson B, Makama M, Mills K, Ammerdorffer A, Gülmezoglu AM, et al. Polyphenols for preeclampsia prevention. BJOG. 2025;132(7). DOI: https://doi.org/10.1111/1471-0528.18106
Ahnemaei FA, Fashami MA, Abdi F, Abbasi M. Factors preventing preeclampsia. Taiwan J Obstet Gynecol. 2020;59(2):173-82. DOI: https://doi.org/10.1016/j.tjog.2020.01.002
Ahn H, Park J, Gilman-Sachs A, Kwak-Kim J. Immunologic characteristics of preeclampsia. Am J Reprod Immunol. 2011;65(4):377-94. DOI: https://doi.org/10.1111/j.1600-0897.2010.00913.x
Brennan LJ, Morton JS, Davidge ST. Vascular dysfunction in preeclampsia. Microcirculation. 2014;21(1):4-14. DOI: https://doi.org/10.1111/micc.12079
Liu W, Zhang M, Feng J, Fan A, Zhou Y, Xu Y. Influence of quercetin on maternal immunity during gestation. Int J Environ Res Public Health. 2017;14(6):592. DOI: https://doi.org/10.3390/ijerph14060592