The Role of Quercetin for the Treatment of Endometriosis and Endometrial Cancer: A Comprehensive Review

Endometrial glands and stroma can be seen outside the uterine cavity in endometriosis, a gynecological disorder linked to estrogen dependency. Hormonal therapies, surgical excision, and non-steroidal anti-inflammatory drug therapy are among the traditional endometriosis treatments, however, various side effects limit their efficacy. Therefore, it is vital to research complementary and alternative therapeutic modalities to decrease the side effects of conventional therapies. While the search for the best endometriosis treatment continues, the focus is being paid to the assistance provided by polyphenols, notably quercetin. A broad spectrum of health-improving benefits of quercetin includes interactions with endometriosis-related molecular targets such as cell proliferation, apoptosis, invasiveness, inflammation, and oxidative stress. According to already-known research, medicines that mimic the physiological effects of quercetin are good candidates for creating novel endometriosis therapies. This review aims to comprehensively review quercetin's potential as a non-pharmacological treatment for endometriosis by interacting with several cellular and molecular targets.

Polyphenol, anti-inflammatory, antioxidant, endometriosis, quercetin, ROS. [1] Zondervan, K.T.; Becker, C.M.; Koga, K.; Missmer, S.A.; Taylor, R.N.; Viganò, P. Endometriosis. Nat. Rev. Dis. Primers, 2018, 4(1), 9. [http://dx.doi.org/10.1038/s41572-018-0008-5] [PMID: 30026507] [http://dx.doi.org/10.1038/s41572-018-0008-5] [PMID: 30026507] [2] Ulukus, M.; Cakmak, H.; Arici, A. The role of endometrium in endometriosis. J. Soc. Gynecol. Investig., 2006, 13(7), 467-476. [http://dx.doi.org/10.1016/j.jsgi.2006.07.005] [PMID: 16990031] [http://dx.doi.org/10.1016/j.jsgi.2006.07.005] [PMID: 16990031] [3] Dawson, A.; Llauradó, F.M.; Anglesio, M.; Yong, P.J.; Carey, M.S. Endometriosis and endometriosis-associated cancers: New insights into the molecular mechanisms of ovarian cancer development. Ecancermedicalscience, 2018, 12, 803. [http://dx.doi.org/10.3332/ecancer.2018.803] [PMID: 29456620] [http://dx.doi.org/10.3332/ecancer.2018.803] [PMID: 29456620] [4] Ruderman, R.; Pavone, M.E. Ovarian cancer in endometriosis: An update on the clinical and molecular aspects. Minerva Ginecol., 2017, 69(3), 286-294. [PMID: 28271698] [PMID: 28271698] [5] Missmer, S.A.; Tu, F.F.; Agarwal, S.K.; Chapron, C.; Soliman, A.M.; Chiuve, S.; Eichner, S.; Flores-Caldera, I.; Horne, A.W.; Kimball, A.B.; Laufer, M.R.; Leyland, N.; Singh, S.S.; Taylor, H.S.; As-Sanie, S. Impact of endometriosis on life-course potential: A narrative review. Int. J. Gen. Med., 2021, 14, 9-25. [http://dx.doi.org/10.2147/IJGM.S261139] [PMID: 33442286] [http://dx.doi.org/10.2147/IJGM.S261139] [PMID: 33442286] [6] Troìa, L.; Luisi, S. Sexual function and quality of life in women with endometriosis. Minerva Obstet. Gynecol., 2022, 74(3), 203-221. [http://dx.doi.org/10.23736/S2724-606X.22.05033-3] [PMID: 35420289] [http://dx.doi.org/10.23736/S2724-606X.22.05033-3] [PMID: 35420289] [7] Giudice, L.C.; Kao, L.C. Endometriosis. Lancet, 2004, 364(9447), 1789-1799. [http://dx.doi.org/10.1016/S0140-6736(04)17403-5] [PMID: 15541453] [http://dx.doi.org/10.1016/S0140-6736(04)17403-5] [PMID: 15541453] [8] Parasar, P.; Ozcan, P.; Terry, K.L. Endometriosis: Epidemiology, diagnosis and clinical management. Curr. Obstet. Gynecol. Rep., 2017, 6(1), 34-41. [http://dx.doi.org/10.1007/s13669-017-0187-1] [PMID: 29276652] [http://dx.doi.org/10.1007/s13669-017-0187-1] [PMID: 29276652] [9] Gupta, D.; Hull, M.L.; Fraser, I.; Miller, L.; Bossuyt, P.M.M.; Johnson, N.; Nisenblat, V. Endometrial biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Libr., 2016, 2016(4), CD012165. [http://dx.doi.org/10.1002/14651858.CD012165] [PMID: 27094925] [http://dx.doi.org/10.1002/14651858.CD012165] [PMID: 27094925] [10] Fischer, C.; Speth, V.; Fleig-Eberenz, S.; Neuhaus, G. Induction of zygotic polyembryos in wheat: Influence of auxin polar transport. Plant Cell, 1997, 9(10), 1767-1780. [http://dx.doi.org/10.2307/3870523] [PMID: 12237347] [http://dx.doi.org/10.2307/3870523] [PMID: 12237347] [11] Bishayee, K.; Ghosh, S.; Mukherjee, A.; Sadhukhan, R.; Mondal, J.; Khuda-Bukhsh, A.R. Quercetin induces cytochrome-c release and ROS accumulation to promote apoptosis and arrest the cell cycle in G2/M, in cervical carcinoma: signal cascade and drug-DNA interaction. Cell Prolif., 2013, 46(2), 153-163. [http://dx.doi.org/10.1111/cpr.12017] [PMID: 23510470] [http://dx.doi.org/10.1111/cpr.12017] [PMID: 23510470] [12] Vidya Priyadarsini, R.; Senthil Murugan, R.; Maitreyi, S.; Ramalingam, K.; Karunagaran, D.; Nagini, S. The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. Eur. J. Pharmacol., 2010, 649(1-3), 84-91. [http://dx.doi.org/10.1016/j.ejphar.2010.09.020] [PMID: 20858478] [http://dx.doi.org/10.1016/j.ejphar.2010.09.020] [PMID: 20858478] [13] Maciejczyk, A.; Surowiak, P. Quercetin inhibits proliferation and increases sensitivity of ovarian cancer cells to cisplatin and paclitaxel. Ginekol. Pol., 2013, 84(7), 590-595. [http://dx.doi.org/10.17772/gp/1609] [PMID: 24032269] [http://dx.doi.org/10.17772/gp/1609] [PMID: 24032269] [14] Pan, H.C.; Jiang, Q.; Yu, Y.; Mei, J.P.; Cui, Y.K.; Zhao, W.J. Quercetin promotes cell apoptosis and inhibits the expression of MMP-9 and fibronectin via the AKT and ERK signalling pathways in human glioma cells. Neurochem. Int., 2015, 80, 60-71. [http://dx.doi.org/10.1016/j.neuint.2014.12.001] [PMID: 25481090] [http://dx.doi.org/10.1016/j.neuint.2014.12.001] [PMID: 25481090] [15] Lou, M.; Zhang, L.; Ji, P.; Feng, F.; Liu, J.; Yang, C.; Li, B.; Wang, L. Quercetin nanoparticles induced autophagy and apoptosis through AKT/ERK/Caspase-3 signaling pathway in human neuroglioma cells: In vitro and in vivo. Biomed. Pharmacother., 2016, 84, 1-9. [http://dx.doi.org/10.1016/j.biopha.2016.08.055] [PMID: 27621033] [http://dx.doi.org/10.1016/j.biopha.2016.08.055] [PMID: 27621033] [16] Catanzaro, D.; Ragazzi, E.; Vianello, C.; Caparrotta, L.; Montopoli, M. Effect of quercetin on cell cycle and cyclin expression in ovarian carcinoma and osteosarcoma cell lines. Nat. Prod. Commun., 2015, 10(8), 1934578X1501000. [http://dx.doi.org/10.1177/1934578X1501000813] [PMID: 26434118] [http://dx.doi.org/10.1177/1934578X1501000813] [PMID: 26434118] [17] Suh, D.K.; Lee, E.J.; Kim, H.C.; Kim, J.H. Induction of G1/S phase arrest and apoptosis by quercetin in human osteosarcoma cells. Arch. Pharm. Res., 2010, 33(5), 781-785. [http://dx.doi.org/10.1007/s12272-010-0519-4] [PMID: 20512478] [http://dx.doi.org/10.1007/s12272-010-0519-4] [PMID: 20512478] [18] Caddeo, C.; Díez-Sales, O.; Pons, R.; Fernàndez-Busquets, X.; Fadda, A.M.; Manconi, M. Topical anti-inflammatory potential of quercetin in lipid-based nanosystems: in vivo and in vitro evaluation. Pharm. Res., 2014, 31(4), 959-968. [http://dx.doi.org/10.1007/s11095-013-1215-0] [PMID: 24297068] [http://dx.doi.org/10.1007/s11095-013-1215-0] [PMID: 24297068] [19] Castangia, I.; Nácher, A.; Caddeo, C.; Valenti, D.; Fadda, A.M.; Díez-Sales, O.; Ruiz-Saurí, A.; Manconi, M. Fabrication of quercetin and curcumin bionanovesicles for the prevention and rapid regeneration of full-thickness skin defects on mice. Acta Biomater., 2014, 10(3), 1292-1300. [http://dx.doi.org/10.1016/j.actbio.2013.11.005] [PMID: 24239901] [http://dx.doi.org/10.1016/j.actbio.2013.11.005] [PMID: 24239901] [20] Alım, Z.; Kılıç, D.; Demir, Y. Some indazoles reduced the activity of human serum paraoxonase 1, an antioxidant enzyme: In vitro inhibition and molecular modeling studies. Arch. Physiol. Biochem., 2019, 125(5), 387-395. [http://dx.doi.org/10.1080/13813455.2018.1470646] [PMID: 29741961] [http://dx.doi.org/10.1080/13813455.2018.1470646] [PMID: 29741961] [21] Demir, Y.; Ceylan, H.; Türkeş, C.; Beydemir, Ş. Molecular docking and inhibition studies of vulpinic, carnosic and usnic acids on polyol pathway enzymes. J. Biomol. Struct. Dyn., 2022, 40(22), 12008-12021. [http://dx.doi.org/10.1080/07391102.2021.1967195] [PMID: 34424822] [http://dx.doi.org/10.1080/07391102.2021.1967195] [PMID: 34424822] [22] Bayrak, S.; Öztürk, C.; Demir, Y.; Alım, Z.; Küfrevioglu, Ö.İ. Purification of polyphenol oxidase from potato and investigation of the inhibitory effects of phenolic acids on enzyme activity. Protein Pept. Lett., 2020, 27(3), 187-192. [http://dx.doi.org/10.2174/0929866526666191002142301] [PMID: 31577197] [http://dx.doi.org/10.2174/0929866526666191002142301] [PMID: 31577197] [23] Zondervan, K.T.; Becker, C.M.; Missmer, S.A. Endometriosis. N. Engl. J. Med., 2020, 382(13), 1244-1256. [http://dx.doi.org/10.1056/NEJMra1810764] [PMID: 32212520] [http://dx.doi.org/10.1056/NEJMra1810764] [PMID: 32212520] [24] Laganà, A.S.; Vitale, S.G.; Granese, R.; Palmara, V.; Ban Frangež, H.; Vrtačnik-Bokal, E.; Chiofalo, B.; Triolo, O. Clinical dynamics of dienogest for the treatment of endometriosis: From bench to bedside. Expert Opin. Drug Metab. Toxicol., 2017, 13(6), 593-596. [http://dx.doi.org/10.1080/17425255.2017.1297421] [PMID: 28537213] [http://dx.doi.org/10.1080/17425255.2017.1297421] [PMID: 28537213] [25] Chew, K.T.; Norsaadah, S.; Suraya, A.; Hing, E.Y.; Ani Amelia, Z.; Nor Azlin, M.I.; Nur Azurah, A.G. Primary umbilical endometriosis successfully treated with dienogest. Horm. Mol. Biol. Clin. Investig., 2017, 29(2), 67-69. [PMID: 27318657] [PMID: 27318657] [26] Raffaelli, R.; Garzon, S.; Baggio, S.; Genna, M.; Pomini, P.; Laganà, A.S.; Ghezzi, F.; Franchi, M. Mesenteric vascular and nerve sparing surgery in laparoscopic segmental intestinal resection for deep infiltrating endometriosis. Eur. J. Obstet. Gynecol. Reprod. Biol., 2018, 231, 214-219. [http://dx.doi.org/10.1016/j.ejogrb.2018.10.057] [PMID: 30415128] [http://dx.doi.org/10.1016/j.ejogrb.2018.10.057] [PMID: 30415128] [27] Kondo, W.; Ribeiro, R.; Zomer, M.T.; Hayashi, R. Laparoscopic double discoid resection with a circular stapler for bowel endometriosis. J. Minim. Invasive Gynecol., 2015, 22(6), 929-931. [http://dx.doi.org/10.1016/j.jmig.2015.04.021] [PMID: 25937595] [http://dx.doi.org/10.1016/j.jmig.2015.04.021] [PMID: 25937595] [28] Palabıyık, E.; Sulumer, A.N.; Uguz, H.; Avcı, B.; Askın, S.; Askın, H.; Demir, Y. Assessment of hypolipidemic and anti-inflammatory properties of walnut (Juglans regia) seed coat extract and modulates some metabolic enzymes activity in triton WR-1339-induced hyperlipidemia in rat kidney, liver, and heart. J. Mol. Recognit., 2023, 36(3), e3004. [http://dx.doi.org/10.1002/jmr.3004] [PMID: 36537558] [http://dx.doi.org/10.1002/jmr.3004] [PMID: 36537558] [29] Özaslan, M.S.; Sağlamtaş, R.; Demir, Y.; Genç, Y.; Saraçoğlu, İ.; Gülçin, İ. Isolation of some phenolic compounds from Plantago subulata L. and determination of their antidiabetic, anticholinesterase, antiepileptic and antioxidant activity. Chem. Biodivers., 2022, 19(8), e202200280. [http://dx.doi.org/10.1002/cbdv.202200280] [PMID: 35796520] [http://dx.doi.org/10.1002/cbdv.202200280] [PMID: 35796520] [30] Forster, R.; Sarginson, A.; Velichkova, A.; Hogg, C.; Dorning, A.; Horne, A.W.; Saunders, P.T.K.; Greaves, E. Macrophage-derived insulin-like growth factor-1 is a key neurotrophic and nerve-sensitizing factor in pain associated with endometriosis. FASEB J., 2019, 33(10), 11210-11222. [http://dx.doi.org/10.1096/fj.201900797R] [PMID: 31291762] [http://dx.doi.org/10.1096/fj.201900797R] [PMID: 31291762] [31] Yu, X.; Wang, Y.; Tan, X.; Li, M. Upregulation of fibroblast growth factor 2 contributes to endometriosis through SPRYs/DUSP6/ERK signaling pathway. Acta Histochem., 2021, 123(5), 151749. [http://dx.doi.org/10.1016/j.acthis.2021.151749] [PMID: 34224989] [http://dx.doi.org/10.1016/j.acthis.2021.151749] [PMID: 34224989] [32] Jeung, I.; Cheon, K.; Kim, M.R. Decreased cytotoxicity of peripheral and peritoneal natural killer cell in endometriosis. BioMed Res. Int., 2016, 2016, 1-6. [http://dx.doi.org/10.1155/2016/2916070] [PMID: 27294113] [http://dx.doi.org/10.1155/2016/2916070] [PMID: 27294113] [33] Malhotra, N.; Karmakar, D.; Tripathi, V.; Luthra, K.; Kumar, S. Correlation of angiogenic cytokines-leptin and IL-8 in stage, type and presentation of endometriosis. Gynecol. Endocrinol., 2012, 28(3), 224-227. [http://dx.doi.org/10.3109/09513590.2011.593664] [PMID: 21848410] [http://dx.doi.org/10.3109/09513590.2011.593664] [PMID: 21848410] [34] Anastasiu, C.V.; Moga, M.A.; Elena Neculau, A.; Bălan, A.; Scârneciu, I.; Dragomir, R.M.; Dull, A.M.; Chicea, L.M. Biomarkers for the noninvasive diagnosis of endometriosis: State of the art and future perspectives. Int. J. Mol. Sci., 2020, 21(5), 1750. [http://dx.doi.org/10.3390/ijms21051750] [PMID: 32143439] [http://dx.doi.org/10.3390/ijms21051750] [PMID: 32143439] [35] Nisenblat, V.; Bossuyt, P.M.M.; Shaikh, R.; Farquhar, C.; Jordan, V.; Scheffers, C.S.; Mol, B.W.J.; Johnson, N.; Hull, M.L. Blood biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Libr., 2016, 2016(5), CD012179. [http://dx.doi.org/10.1002/14651858.CD012179] [PMID: 27132058] [http://dx.doi.org/10.1002/14651858.CD012179] [PMID: 27132058] [36] Kapoor, R.; Sirohi, V.K.; Gupta, K.; Dwivedi, A. Naringenin ameliorates progression of endometriosis by modulating Nrf2/Keap1/HO1 axis and inducing apoptosis in rats. J. Nutr. Biochem., 2019, 70, 215-226. [http://dx.doi.org/10.1016/j.jnutbio.2019.05.003] [PMID: 31252288] [http://dx.doi.org/10.1016/j.jnutbio.2019.05.003] [PMID: 31252288] [37] Kobayashi, H.; Kimura, M.; Maruyama, S.; Nagayasu, M.; Imanaka, S. Revisiting estrogen-dependent signaling pathways in endometriosis: Potential targets for non-hormonal therapeutics. Eur. J. Obstet. Gynecol. Reprod. Biol., 2021, 258, 103-110. [http://dx.doi.org/10.1016/j.ejogrb.2020.12.044] [PMID: 33421806] [http://dx.doi.org/10.1016/j.ejogrb.2020.12.044] [PMID: 33421806] [38] Yang, H.; Hu, T.; Hu, P.; Qi, C.; Qian, L. miR-143-3p inhibits endometriotic stromal cell proliferation and invasion by inactivating autophagy in endometriosis. Mol. Med. Rep., 2021, 23(5), 356. [http://dx.doi.org/10.3892/mmr.2021.11995] [PMID: 33760149] [http://dx.doi.org/10.3892/mmr.2021.11995] [PMID: 33760149] [39] Abe, W.; Nasu, K.; Nakada, C.; Kawano, Y.; Moriyama, M.; Narahara, H. miR-196b targets c-myc and Bcl-2 expression, inhibits proliferation and induces apoptosis in endometriotic stromal cells. Hum. Reprod., 2013, 28(3), 750-761. [http://dx.doi.org/10.1093/humrep/des446] [PMID: 23293219] [http://dx.doi.org/10.1093/humrep/des446] [PMID: 23293219] [40] Orellana, R.; García-Solares, J.; Donnez, J.; van Kerk, O.; Dolmans, M.M.; Donnez, O. Important role of collective cell migration and nerve fiber density in the development of deep nodular endometriosis. Fertil. Steril., 2017, 107(4), 987-995.e5. [http://dx.doi.org/10.1016/j.fertnstert.2017.01.005] [PMID: 28238494] [http://dx.doi.org/10.1016/j.fertnstert.2017.01.005] [PMID: 28238494] [41] Donnez, O.; Soares, M.; Defrère, S.; Dehoux, J.P.; van Langendonckt, A.; Donnez, J.; Dolmans, M.M.; Colette, S. Nerve fiber density in deep nodular endometriotic lesions induced in a baboon experimental model. Fertil. Steril., 2013, 100(4), 1144-1150.e2. [http://dx.doi.org/10.1016/j.fertnstert.2013.06.014] [PMID: 23850304] [http://dx.doi.org/10.1016/j.fertnstert.2013.06.014] [PMID: 23850304] [42] Donnez, J.; Smoes, P.; Gillerot, S.; Casanas-Roux, F.; Nisolle, M. Vascular endothelial growth factor (VEGF) in endometriosis. Hum. Reprod., 1998, 13(6), 1686-1690. [http://dx.doi.org/10.1093/humrep/13.6.1686] [PMID: 9688413] [http://dx.doi.org/10.1093/humrep/13.6.1686] [PMID: 9688413] [43] Bourlev, V.; Volkov, N.; Pavlovitch, S.; Lets, N.; Larsson, A.; Olovsson, M. The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions. Reproduction, 2006, 132(3), 501-509. [http://dx.doi.org/10.1530/rep.1.01110] [PMID: 16940291] [http://dx.doi.org/10.1530/rep.1.01110] [PMID: 16940291] [44] Zhang, M.; Xu, T.; Tong, D.; Li, S.; Yu, X.; Liu, B.; Jiang, L.; Liu, K. Research advances in endometriosis-related signaling pathways: A review. Biomed. Pharmacother., 2023, 164, 114909. [http://dx.doi.org/10.1016/j.biopha.2023.114909] [PMID: 37210898] [http://dx.doi.org/10.1016/j.biopha.2023.114909] [PMID: 37210898] [45] Chen, L.H.; Lo, W.C.; Huang, H.Y.; Wu, H.M. A lifelong impact on endometriosis: Pathophysiology and pharmacological treatment. Int. J. Mol. Sci., 2023, 24(8), 7503. [http://dx.doi.org/10.3390/ijms24087503] [PMID: 37108664] [http://dx.doi.org/10.3390/ijms24087503] [PMID: 37108664] [46] Park, J.K.; Song, M.; Dominguez, C.E.; Walter, M.F.; Santanam, N.; Parthasarathy, S.; Murphy, A.A. Glycodelin mediates the increase in vascular endothelial growth factor in response to oxidative stress in the endometrium. Am. J. Obstet. Gynecol., 2006, 195(6), 1772-1777. [http://dx.doi.org/10.1016/j.ajog.2006.07.025] [PMID: 17132480] [http://dx.doi.org/10.1016/j.ajog.2006.07.025] [PMID: 17132480] [47] Brunty, S.; Santanam, N. Current assessment of the (dys)function of macrophages in endometriosis and its associated pain. Ann. Transl. Med., 2019, 7(S8), S381. [http://dx.doi.org/10.21037/atm.2019.12.119] [PMID: 32016099] [http://dx.doi.org/10.21037/atm.2019.12.119] [PMID: 32016099] [48] Gupta, S.; Agarwal, A.; Krajcir, N.; Alvarez, J.G. Role of oxidative stress in endometriosis. Reprod. Biomed. Online, 2006, 13(1), 126-134. [http://dx.doi.org/10.1016/S1472-6483(10)62026-3] [PMID: 16820124] [http://dx.doi.org/10.1016/S1472-6483(10)62026-3] [PMID: 16820124] [49] Agarwal, A.; Gupta, S.; Sharma, R.K. Role of oxidative stress in female reproduction. Reprod. Biol. Endocrinol., 2005, 3(1), 28. [http://dx.doi.org/10.1186/1477-7827-3-28] [PMID: 16018814] [http://dx.doi.org/10.1186/1477-7827-3-28] [PMID: 16018814] [50] Demir, Y. Naphthoquinones, benzoquinones, and anthraquinones: Molecular docking, ADME and inhibition studies on human serum paraoxonase-1 associated with cardiovascular diseases. Drug Dev. Res., 2020, 81(5), 628-636. [http://dx.doi.org/10.1002/ddr.21667] [PMID: 32232985] [http://dx.doi.org/10.1002/ddr.21667] [PMID: 32232985] [51] Beydemir, Ş.; Demir, Y. Antiepileptic drugs: Impacts on human serum paraoxonase-1. J. Biochem. Mol. Toxicol., 2017, 31(6), e21889. [http://dx.doi.org/10.1002/jbt.21889] [PMID: 28032682] [http://dx.doi.org/10.1002/jbt.21889] [PMID: 28032682] [52] Demir, Y. The behaviour of some antihypertension drugs on human serum paraoxonase-1: An important protector enzyme against atherosclerosis. J. Pharm. Pharmacol., 2019, 71(10), 1576-1583. [http://dx.doi.org/10.1111/jphp.13144] [PMID: 31347707] [http://dx.doi.org/10.1111/jphp.13144] [PMID: 31347707] [53] Türkeş, C.; Demir, Y.; Beydemir, Ş. Some calcium-channel blockers: Kinetic and in silico studies on paraoxonase-I. J. Biomol. Struct. Dyn., 2022, 40(1), 77-85. [http://dx.doi.org/10.1080/07391102.2020.1806927] [PMID: 32783605] [http://dx.doi.org/10.1080/07391102.2020.1806927] [PMID: 32783605] [54] Korkmaz, I.N.; Türkeş, C.; Demir, Y.; Öztekin, A.; Özdemir, H.; Beydemir, Ş. Biological evaluation and in silico study of benzohydrazide derivatives as paraoxonase 1 inhibitors. J. Biochem. Mol. Toxicol., 2022, 36(11), e23180. [http://dx.doi.org/10.1002/jbt.23180] [PMID: 35916346] [http://dx.doi.org/10.1002/jbt.23180] [PMID: 35916346] [55] Burton, G.J.; Jauniaux, E. Oxidative stress. Best Pract. Res. Clin. Obstet. Gynaecol., 2011, 25(3), 287-299. [http://dx.doi.org/10.1016/j.bpobgyn.2010.10.016] [PMID: 21130690] [http://dx.doi.org/10.1016/j.bpobgyn.2010.10.016] [PMID: 21130690] [56] Scutiero, G.; Iannone, P.; Bernardi, G.; Bonaccorsi, G.; Spadaro, S.; Volta, C.A.; Greco, P.; Nappi, L. Oxidative stress and endometriosis: A systematic review of the literature. Oxid. Med. Cell. Longev., 2017, 2017, 1-7. [http://dx.doi.org/10.1155/2017/7265238] [PMID: 29057034] [http://dx.doi.org/10.1155/2017/7265238] [PMID: 29057034] [57] Li, Y.; Cai, L.; Guo, N.; Liu, C.; Wang, M.; Zhu, L.; Li, F.; Jin, L.; Sui, C. Oviductal extracellular vesicles from women with endometriosis impair embryo development. Front. Endocrinol., 2023, 14, 1171778. [http://dx.doi.org/10.3389/fendo.2023.1171778] [PMID: 37409222] [http://dx.doi.org/10.3389/fendo.2023.1171778] [PMID: 37409222] [58] Zhang, M.; Liu, C.; Yuan, X.Q.; Cui, F.P.; Miao, Y.; Yao, W.; Qin, D.Y.; Deng, Y.L.; Chen, P.P.; Zeng, J.Y.; Liu, X.Y.; Wu, Y.; Li, C.R.; Lu, W.Q.; Li, Y.F.; Zeng, Q. Oxidatively generated DNA damage mediates the associations of exposure to phthalates with uterine fibroids and endometriosis: Findings from TREE cohort. Free Radic. Biol. Med., 2023, 205, 69-76. [http://dx.doi.org/10.1016/j.freeradbiomed.2023.05.029] [PMID: 37279842] [http://dx.doi.org/10.1016/j.freeradbiomed.2023.05.029] [PMID: 37279842] [59] Wingfield, M.; Macpherson, A.; Healy, D.L.; Rogers, P.A.W. Cell proliferation is increased in the endometrium of women with endometriosis. Fertil. Steril., 1995, 64(2), 340-346. [http://dx.doi.org/10.1016/S0015-0282(16)57733-4] [PMID: 7542208] [http://dx.doi.org/10.1016/S0015-0282(16)57733-4] [PMID: 7542208] [60] Jürgensen, A.; Mettler, L.; Volkov, N.I.; Parwaresch, R. Proliferative activity of the endometrium throughout the menstrual cycle in infertile women with and without endometriosis. Fertil. Steril., 1996, 66(3), 369-375. [http://dx.doi.org/10.1016/S0015-0282(16)58502-1] [PMID: 8751731] [http://dx.doi.org/10.1016/S0015-0282(16)58502-1] [PMID: 8751731] [61] Nasiri, N.; Moini, A.; Eftekhari-Yazdi, P.; Karimian, L.; Salman-Yazdi, R.; Arabipoor, A. Oxidative stress statues in serum and follicular fluid of women with endometriosis. Cell J., 2017, 18(4), 582-587. [PMID: 28042542] [PMID: 28042542] [62] Várnagy, Á.; Kőszegi, T.; Györgyi, E.; Szegedi, S.; Sulyok, E.; Prémusz, V.; Bódis, J. Levels of total antioxidant capacity and 8-hydroxy-2′-deoxyguanosine of serum and follicular fluid in women undergoing in vitro fertilization: Focusing on endometriosis. Hum. Fertil., 2020, 23(3), 200-208. [http://dx.doi.org/10.1080/14647273.2018.1535719] [PMID: 30422732] [http://dx.doi.org/10.1080/14647273.2018.1535719] [PMID: 30422732] [63] Mori, M.; Ito, F.; Shi, L.; Wang, Y.; Ishida, C.; Hattori, Y.; Niwa, M.; Hirayama, T.; Nagasawa, H.; Iwase, A.; Kikkawa, F.; Toyokuni, S. Ovarian endometriosis-associated stromal cells reveal persistently high affinity for iron. Redox Biol., 2015, 6, 578-586. [http://dx.doi.org/10.1016/j.redox.2015.10.001] [PMID: 26498255] [http://dx.doi.org/10.1016/j.redox.2015.10.001] [PMID: 26498255] [64] Woo, J.H.; Choi, Y.S.; Choi, J.H. Iron-storage protein ferritin is upregulated in endometriosis and iron overload contributes to a migratory phenotype. Biomedicines, 2020, 8(11), 454. [http://dx.doi.org/10.3390/biomedicines8110454] [PMID: 33121166] [http://dx.doi.org/10.3390/biomedicines8110454] [PMID: 33121166] [65] Ng, S.W.; Norwitz, S.G.; Taylor, H.S.; Norwitz, E.R. Endometriosis: The role of iron overload and ferroptosis. Reprod. Sci., 2020, 27(7), 1383-1390. [http://dx.doi.org/10.1007/s43032-020-00164-z] [PMID: 32077077] [http://dx.doi.org/10.1007/s43032-020-00164-z] [PMID: 32077077] [66] Pirdel, L.; Pirdel, M. Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis. Reproduction, 2014, 147(6), R199-R207. [http://dx.doi.org/10.1530/REP-13-0552] [PMID: 24599836] [http://dx.doi.org/10.1530/REP-13-0552] [PMID: 24599836] [67] Nanda, A.; K, T.; Banerjee, P.; Dutta, M.; Wangdi, T.; Sharma, P.; Chaudhury, K.; Jana, S.K. Cytokines, angiogenesis, and extracellular matrix degradation are augmented by oxidative stress in endometriosis. Ann. Lab. Med., 2020, 40(5), 390-397. [http://dx.doi.org/10.3343/alm.2020.40.5.390] [PMID: 32311852] [http://dx.doi.org/10.3343/alm.2020.40.5.390] [PMID: 32311852] [68] Huang, F.; Cao, J.; Liu, Q.; Zou, Y.; Li, H.; Yin, T. MAPK/ERK signal pathway involved expression of COX-2 and VEGF by IL-1β induced in human endometriosis stromal cells in vitro. Int. J. Clin. Exp. Pathol., 2013, 6(10), 2129-2136. [PMID: 24133591] [PMID: 24133591] [69] Qiu, X.M.; Lai, Z.Z.; Ha, S.Y.; Yang, H.L.; Liu, L.B.; Wang, Y.; Shi, J.W.; Ruan, L.Y.; Ye, J.F.; Wu, J.N.; Fu, Q.; Yi, X.F.; Chang, K.K.; Li, M.Q. IL-2 and IL-27 synergistically promote growth and invasion of endometriotic stromal cells by maintaining the balance of IFN-γ and IL-10 in endometriosis. Reproduction, 2020, 159(3), 251-260. [http://dx.doi.org/10.1530/REP-19-0411] [PMID: 31869309] [http://dx.doi.org/10.1530/REP-19-0411] [PMID: 31869309] [70] González-Ramos, R.; Defrère, S.; Devoto, L. Nuclear factor–kappaB: A main regulator of inflammation and cell survival in endometriosis pathophysiology. Fertil. Steril., 2012, 98(3), 520-528. [http://dx.doi.org/10.1016/j.fertnstert.2012.06.021] [PMID: 22771029] [http://dx.doi.org/10.1016/j.fertnstert.2012.06.021] [PMID: 22771029] [71] González-Ramos, R.; Rocco, J.; Rojas, C.; Sovino, H.; Poch, A.; Kohen, P.; Alvarado-Díaz, C.; Devoto, L. Physiologic activation of nuclear factor kappa-B in the endometrium during the menstrual cycle is altered in endometriosis patients. Fertil. Steril., 2012, 97(3), 645-651. [http://dx.doi.org/10.1016/j.fertnstert.2011.12.006] [PMID: 22196717] [http://dx.doi.org/10.1016/j.fertnstert.2011.12.006] [PMID: 22196717] [72] Giordano, A.; Tommonaro, G. Curcumin and cancer. Nutrients, 2019, 11(10), 2376. [http://dx.doi.org/10.3390/nu11102376] [PMID: 31590362] [http://dx.doi.org/10.3390/nu11102376] [PMID: 31590362] [73] Shakeri, A.; Ward, N.; Panahi, Y.; Sahebkar, A. Anti-angiogenic activity of curcumin in cancer therapy: A narrative review. Curr. Vasc. Pharmacol., 2019, 17(3), 262-269. [http://dx.doi.org/10.2174/1570161116666180209113014] [PMID: 29424316] [http://dx.doi.org/10.2174/1570161116666180209113014] [PMID: 29424316] [74] Wei, X.; Shao, X. Nobiletin alleviates endometriosis via down-regulating NF-κB activity in endometriosis mouse model. Biosci. Rep., 2018, 38(3), BSR20180470. [http://dx.doi.org/10.1042/BSR20180470] [http://dx.doi.org/10.1042/BSR20180470] [75] Kumar, P.; Amreen, S.; Gupta, P.; Rao, P. Evaluation of oxidative stress and severity of endometriosis. J. Hum. Reprod. Sci., 2019, 12(1), 40-46. [http://dx.doi.org/10.4103/jhrs.JHRS_27_17] [PMID: 31007466] [http://dx.doi.org/10.4103/jhrs.JHRS_27_17] [PMID: 31007466] [76] Szczepańska, M.; Koźlik, J.; Skrzypczak, J.; Mikołajczyk, M. Oxidative stress may be a piece in the endometriosis puzzle. Fertil. Steril., 2003, 79(6), 1288-1293. [http://dx.doi.org/10.1016/S0015-0282(03)00266-8] [PMID: 12798872] [http://dx.doi.org/10.1016/S0015-0282(03)00266-8] [PMID: 12798872] [77] Jamali, N.; Zal, F.; Mostafavi-Pour, Z.; Samare-Najaf, M.; Poordast, T.; Dehghanian, A. Ameliorative effects of quercetin and metformin and their combination against experimental endometriosis in rats. Reprod. Sci., 2021, 28(3), 683-692. [http://dx.doi.org/10.1007/s43032-020-00377-2] [PMID: 33141412] [http://dx.doi.org/10.1007/s43032-020-00377-2] [PMID: 33141412] [78] Fadin, M.; Nicoletti, M.C.; Pellizzato, M.; Accardi, M.; Baietti, M.G.; Fratter, A. Effectiveness of the integration of quercetin, turmeric, and N-acetylcysteine in reducing inflammation and pain associated with endometriosis. In vitro and in vivo studies. Minerva Ginecol., 2020, 72(5), 285-291. [http://dx.doi.org/10.23736/S0026-4784.20.04615-8] [PMID: 32921020] [http://dx.doi.org/10.23736/S0026-4784.20.04615-8] [PMID: 32921020] [79] Park, S.; Lim, W.; Bazer, F.W.; Whang, K.Y.; Song, G. Quercetin inhibits proliferation of endometriosis regulating cyclin D1 and its target microRNAs in vitro and in vivo. J. Nutr. Biochem., 2019, 63, 87-100. [http://dx.doi.org/10.1016/j.jnutbio.2018.09.024] [PMID: 30359864] [http://dx.doi.org/10.1016/j.jnutbio.2018.09.024] [PMID: 30359864] [80] Signorile, P.G.; Viceconte, R.; Baldi, A. Novel dietary supplement association reduces symptoms in endometriosis patients. J. Cell. Physiol., 2018, 233(8), 5920-5925. [http://dx.doi.org/10.1002/jcp.26401] [PMID: 29243819] [http://dx.doi.org/10.1002/jcp.26401] [PMID: 29243819] [81] Cao, Y.; Zhuang, M.; Yang, Y.; Xie, S.; Cui, J.; Cao, L.; Zhang, T.; Zhu, Y. Preliminary study of quercetin affecting the hypothalamic-pituitary-gonadal axis on rat endometriosis model. Evid. Based Complement. Alternat. Med., 2014, 2014, 1-12. [http://dx.doi.org/10.1155/2014/781684] [PMID: 25530789] [http://dx.doi.org/10.1155/2014/781684] [PMID: 25530789] [82] Zhang, X; Wang, X; Wang, HJ; Yang, Q; Qie, MR Inhibition effect and mechanisms of quercetin on surgically induced endometriosis. Sichuan Da Xue Xue Bao Yi Xue Ban., 2009, 40(2), 228-31, 244. [83] Ilhan, M.; Ali, Z.; Khan, I.A.; Taştan, H.; Küpeli Akkol, E. The regression of endometriosis with glycosylated flavonoids isolated from Melilotus officinalis (L.) Pall. in an endometriosis rat model. Taiwan. J. Obstet. Gynecol., 2020, 59(2), 211-219. [http://dx.doi.org/10.1016/j.tjog.2020.01.008] [PMID: 32127140] [http://dx.doi.org/10.1016/j.tjog.2020.01.008] [PMID: 32127140] [84] Li, X.; Zhu, Q.; Ma, M.; Guo, H. Quercetin inhibits the progression of endometrial HEC-1-A cells by regulating ferroptosis-a preliminary study. Eur. J. Med. Res., 2022, 27(1), 292. [http://dx.doi.org/10.1186/s40001-022-00934-2] [PMID: 36522794] [http://dx.doi.org/10.1186/s40001-022-00934-2] [PMID: 36522794] [85] Cebecioglu, R.; Yildirim, M.; Akagunduz, D.; Korkmaz, I.; Tekin, H.O.; Atasever-Arslan, B.; Catal, T. Synergistic effects of quercetin and selenium on oxidative stress in endometrial adenocarcinoma cells. Bratisl. Med. J., 2019, 120(6), 449-455. [http://dx.doi.org/10.4149/BLL_2019_072] [PMID: 31223026] [http://dx.doi.org/10.4149/BLL_2019_072] [PMID: 31223026] [86] Scambia, G.; Ranelletti, F.O.; Panici, P.B.; Piantelli, M.; Bonanno, G.; De Vincenzo, R.; Ferrandina, G.; Maggiano, N.; Capelli, A.; Mancuso, S. Inhibitory effect of quercetin on primary ovarian and endometrial cancers and synergistic activity with cis-diamminedichloroplatinum(II). Gynecol. Oncol., 1992, 45(1), 13-19. [http://dx.doi.org/10.1016/0090-8258(92)90484-Z] [PMID: 1601330] [http://dx.doi.org/10.1016/0090-8258(92)90484-Z] [PMID: 1601330] 63 2