REVIEW Overview of biological effects of Quercetin on ovary Zahra Rashidi 1 | Zahra Khosravizadeh 2 | Ali Talebi 3,4 | Kajal Khodamoradi 2 | Reyhane Ebrahimi 5,6 | Fardin Amidi 2,4,7 1 Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran 2 Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 3 School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran 4 Sexual Health and Fertility Research Center, Shahroud University of Medical Sciences, Shahroud, Iran 5 Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 6 Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran 7 Department of Infertility, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Correspondence Fardin Amidi, Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Pour Sina St, Tehran, 1417613151, Iran; Department of Infertility, Shariati Hospital, Tehran University of Medical Sciences, Tehran, 1411713135, Iran. Email: famidi@sina.tums.ac.ir, famidi@tums. ac.ir Over the last few decades, using natural products has been increased to treat differ- ent diseases. Today, great attention has been pointed toward the usage of natural products such as flavonoids, especially Quercetin (QUR), in the treatment of diseases. QUR as a natural antioxidant has been traditionally used to prevent or treat a variety of diseases such as cancer, cardiovascular disease, polycystic ovary syndrome (PCOS), obesity, chronic inflammation, and reproductive system dysfunction. Several studies demonstrated that QUR acts as an anti-inflammatory, anti-apoptotic, antioxi- dant, and anticancer agent. With this in view, in this study, we intended to describe an overview of the biological effects of QUR on the ovary. QUR improves the quality of oocytes and embryos. It affects the proliferation and apoptosis and decreases the oxidative stress in granulosa cells (GCs). Furthermore, QUR can be used as a comple- mentary and alternative therapy in ovarian cancer and it has beneficial effects in the treatment of PCOS patients. It seems that QUR as a supplementary factor has differ- ent activities for the treatment of different disorders and it also has bidirectional activities. However, further investigations are needed for understanding the efficacy of QUR in the treatment and improvement of gynecological patients. KEYWORDS Granulosa cell, oocyte, ovarian cancer, polycystic ovary syndrome, quercetin Abbreviations: 17β-HSD1, 17 β-hydroxysteroid dehydrogenase type 1; 2008/C13, human ovarian carcinoma; 3 0 UTR, 3 0 untranslated region; A2780/CP70, human ovarian cancer cell line; AKT, protein kinase B; AP-1, activator protein-1; Bax, Bcl-2-Associated X Protein; Bcl-2, B-cell lymphoma 2; BLF, Chinese Bayberry leave flavonoids; C13, CDDP-resistant variant; C13*, human epithelial ovarian cancer; cAMP, cyclic adenosine monophosphate; CHOP, CCAAT-enhancer-binding protein homologous protein; circRNAs, circular RNAs; COX, cyclooxygenase; CRP, C-reactive proteins; DBP, diastolic blood pressure; EDs, endocrine disruptors; ER α, estrogen receptors alpha; ERK, extracellular signal-related kinase; ERS, endoplasmic reticulum stress; FSH, follicle-stimulating hormone; FTIs, farnesyltransferase inhibitors; G0, Gap0; G1, Gap1; GCs, granulosa cells; GnRH, gonadotropin-releasing hormone; GPx, glutathione peroxidase; GSH, glutamate-stimulating hormones; GSS, glutathione synthetase; GST, glutathione S-transferase; HSP70, heat shock protein 70; ICAM-1, intercellular adhesion molecule 1; IGF-1, insulin-like growth factor 1; IMA, ischemia modified albumin; IUPAC, International Union of Pure and Applied Chemistry; IVM, in vitro maturation; JNK, c-Jun NH2-terminal kinase; Keap1, Kelch-like Ech-associated protein 1; LH, luteinizing hormone; LH4, the monofunctional platinum tris (benzimidazole) monochloroplatinum (II) chloride; LH6, the monofunctional platinum complex tris (imidazo(1,2-Α)pyridine) chloroplatinum(II) chloride; lncRNAs, long noncoding RNAs; LPS, lipopolysaccharide; M, mitosis; MPEG-PCL, monomethoxy poly(ethylene glycol)-poly(epsilon- caprolactone); MPF, maturation promoting factor; NF-κB, nuclear factor-κB; NO, nitric oxide; NQO1, NAD(P)H, quinone oxidoreductase 1; Nrf2-ARE, nuclear factor (erythroid-derived 2)-like 2/antioxidant response element; PCNA, proliferating cell nuclear antigen; PCOS, polycystic ovary syndrome; PPARγ, peroxisome proliferator-activated receptor c; PR, progesterone receptor; P-ris, primary cancer cells; QUR, Quercetin; RCTs, randomized controlled trials; ROS/RNS, reactive oxygen/nitrogen species; SBP, systolic blood pressure; SKOV3/CDDP, ovarian carcinoma (SKOV3)/cisplatin (CDDP)-resistant counterparts (SKOV3/CDDP); SOD, superoxide dismutase; STAT3, signal transducer and activator of transcription 3; TAS, total antioxidant status; TGF β1, transforming growth factor; TNF-R, tumor necrosis factor receptors; Topo I and Topo II, topoisomerases I and II; TRAIL, tumor necrosis factor related apoptosis-inducing ligand; Trx, thioredoxin; type II EBS, type II estrogen binding site; VCAM-1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor. Received: 19 December 2019 Revised: 14 April 2020 Accepted: 13 May 2020 DOI: 10.1002/ptr.6750 Phytotherapy Research. 2020;1–17. wileyonlinelibrary.com/journal/ptr © 2020 John Wiley & Sons, Ltd. 1