Research Progress on Oxidative Stress Mechanisms and Antioxidant Therapy in Endometriosis

doi:10.12280/gjfckx.20250980

Abstract

Abstract:

Endometriosis is a common and complex gynecological disease, closely associated with chronic pelvic pain and infertility. Oxidative stress plays an important role in the pathogenesis of endometriosis. It promotes the progression of endometriotic lesions through mechanisms such as generating excessive reactive oxygen species, triggering inflammation, and inducing iron overload. Antioxidants including vitamin C, vitamin E, melatonin, Lycium barbarum polysaccharide, curcumin, resveratrol, and baicalein can inhibit the progression of endometriosis, alleviate pain symptoms, and improve fertility by scavenging reactive oxygen species, suppressing oxidative stress and inflammatory responses, and regulating apoptosis. By summarizing the relevant research progress, this review aims to deepen the understanding of the mechanisms of endometriosis to guide individualized treatment, promote the application of novel antioxidants in the treatment of endometriosis, and provide evidence-based support for clinical practice.

Key words: Endometriosis, Oxidative stress, Antioxidants, Inflammation, Ferroptosis

HAN Zhao-xun, ZHOU Ye. Research Progress on Oxidative Stress Mechanisms and Antioxidant Therapy in Endometriosis[J]. Journal of International Obstetrics and Gynecology, 2026, 53(2): 125-130.

References 40

[1]	Giudice LC, Horne AW, Missmer SA. Time for global health policy and research leaders to prioritize endometriosis[J]. Nat Commun, 2023, 14(1):8028. doi: 10.1038/s41467-023-43913-9. pmid: 38049392
[2]	Gao Q, Wang M, Cao WJ, et al. Salusin α counteracts salusin β to attenuate artery medial calcification through the inhibition of oxidative stress and extracellular signal-regulated protein kinases signaling pathway in rats with chronic kidney disease[J]. J Pharmacol Exp Ther, 2025, 393(1):103793. doi: 10.1016/j.jpet.2025.103793.
[3]	苏吾德, 王雁, 赵勇. 抗氧化剂在糖尿病视网膜病变中的机制研究与治疗潜力探讨[J]. 中国现代医生, 2025, 63(33):125-127,132. doi: 10.3969/j.issn.1673-9701.2025.33.026.
[4]	Li S, Fan Y, Shu C, et al. Methyl 3,4-dihydroxybenzoate alleviates oxidative damage in granulosa cells by activating Nrf2 antioxidant pathway[J]. J Ovarian Res, 2024, 17(1):87. doi: 10.1186/s13048-024-01412-5. pmid: 38664755
[5]	Amreen S, Kumar P, Gupta P, et al. Evaluation of Oxidative Stress and Severity of Endometriosis[J]. J Hum Reprod Sci, 2019, 12(1):40-46. doi: 10.4103/jhrs.JHRS_27_17. pmid: 31007466
[6]	Guo F, Zong S, Zhang X, et al. Ferroptosis and metastasis: molecular checkpoints, microenvironmental dynamics, and therapeutic opportunities[J]. Mol Cancer, 2026, 25(1):45. doi: 10.1186/s12943-025-02544-y.
[7]	Tan H, Ji Y, Cheng X, et al. Chlorogenic acid alleviates chronic restraint stress-induced liver injury potentially via Nrf2-mediated inhibition of ferroptosis and mitochondrial apoptosis[J]. Food Funct, 2026, 17(2):1061-1073. doi: 10.1039/d5fo04627k.
[8]	Ni C, Li D. Ferroptosis and oxidative stress in endometriosis: A systematic review of the literature[J]. Medicine(Baltimore), 2024, 103(11):e37421. doi: 10.1097/MD.0000000000037421.
[9]	Ni Z, Li Y, Song D, et al. Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity[J]. Cell Death Dis, 2022, 13(7):579. doi: 10.1038/s41419-022-05037-8. pmid: 35787614
[10]	Neri M, Sanna E, Ferrari PA, et al. Divergent Immune-Metabolic Profiles in Endometriosis and Ovarian Cancer: A Cross-Sectional Analysis[J]. Cancers(Basel), 2025, 17(14):2325. doi: 10.3390/cancers17142325.
[11]	Luo Y, Li L, Hu Q, et al. Iron overload increases the sensitivity of endometriosis stromal cells to ferroptosis via a PRC2-independent function of EZH2[J]. Int J Biochem Cell Biol, 2024, 169:106553. doi: 10.1016/j.biocel.2024.106553.
[12]	Yang F, Liu D, Hu L, et al. EGR1 promotes ferroptosis in endometriosis through transcriptional activation of HMOX1[J]. Mol Cell Endocrinol, 2026, 613:112721. doi: 10.1016/j.mce.2025.112721.
[13]	Li S, Zhou Y, Huang Q, et al. Iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by HMOX1[J]. Cell Death Discov, 2021, 7(1):355. doi: 10.1038/s41420-021-00751-2. pmid: 34782602
[14]	Lv H, Liu B, Dai Y, et al. TET3-overexpressing macrophages promote endometriosis[J]. J Clin Invest, 2024, 134(21):e181839. doi: 10.1172/JCI181839.
[15]	Woo JH, Yang YI, Ahn JH, et al. Interleukin 6 secretion from alternatively activated macrophages promotes the migration of endometriotic epithelial cells[J]. Biol Reprod, 2017, 97(5):660-670. doi: 10.1093/biolre/iox118.
[16]	Burdan O, Picheta N, Piekarz J, et al. Mechanistic Insights into the Anti-Inflammatory and Anti-Proliferative Effects of Selected Medicinal Plants in Endometriosis[J]. Int J Mol Sci, 2025, 26(22):10947. doi: 10.3390/ijms262210947.
[17]	Timoshnikov VA, Kobzeva TV, Polyakov NE, et al. Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone[J]. Int J Mol Sci, 2020, 21(11):3967. doi: 10.3390/ijms21113967.
[18]	Jiang Q. Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy[J]. Free Radic Biol Med, 2014, 72:76-90. doi: 10.1016/j.freeradbiomed.2014.03.035.
[19]	Tao R, Zhang Q, Duan J, et al. Construction and evaluation of an antioxidant synergistic system containing vitamin C and vitamin E[J]. J Microencapsul, 2023, 40(3):157-170. doi: 10.1080/02652048.2023.2183276.
[20]	Luo H, Li X, Lao T, et al. Inverse association between dietary antioxidant intake and endometriosis among US women: A cross-sectional NHANES study[J]. Eur J Obstet Gynecol Reprod Biol, 2025, 312:114535. doi: 10.1016/j.ejogrb.2025.114535.
[21]	Bayu P, Wibisono JJ. Vitamin C and E antioxidant supplementation may significantly reduce pain symptoms in endometriosis: A systematic review and meta-analysis of randomized controlled trials[J]. PLoS One, 2024, 19(5):e0301867. doi: 10.1371/journal.pone.0301867.
[22]	Hosseinzadeh A, Alinaghian N, Sheibani M, et al. Melatonin: Current evidence on protective and therapeutic roles in gynecological diseases[J]. Life Sci, 2024, 344:122557. doi: 10.1016/j.lfs.2024.122557.
[23]	王剑, 杨佳澄, 高丽娜, 等. 褪黑素通过NF-κB/NLRP3信号抑制子宫内膜异位症的进展机制研究[J]. 实用妇产科杂志, 2024, 40(4):310-315.
[24]	Ge L, Yang Y, Gao Y, et al. Ovarian Endometrioma Disrupts Oocyte-Cumulus Communication and Mitochondrial Function, With Melatonin Mitigating the Effects[J]. Cell Prolif, 2025, 58(4):e13800. doi: 10.1111/cpr.13800.
[25]	Qi S, Yan L, Liu Z, et al. Melatonin inhibits 17β-estradiol-induced migration, invasion and epithelial-mesenchymal transition in normal and endometriotic endometrial epithelial cells[J]. Reprod Biol Endocrinol, 2018, 16(1):62. doi: 10.1186/s12958-018-0375-5.
[26]	Wang J, Li S, Zhang H, et al. A review of Lycium barbarum polysaccharides: Extraction, purification, structural-property relationships, and bioactive molecular mechanisms[J]. Carbohydr Res, 2024, 544:109230. doi: 10.1016/j.carres.2024.109230.
[27]	Xu L, Liu H, Rang Y, et al. Lycium barbarum polysaccharides attenuate nonylphenol and octylphenol-induced oxidative stress and neurotransmitter disorders in PC-12 cells[J]. Toxicology, 2024, 505:153808. doi: 10.1016/j.tox.2024.153808.
[28]	Jiang SJ, Xiao X, Li J, et al. Lycium barbarum polysaccharide-glycoprotein ameliorates ionizing radiation-induced epithelial injury by regulating oxidative stress and ferroptosis via the Nrf2 pathway[J]. Free Radic Biol Med, 2023, 204:84-94. doi: 10.1016/j.freeradbiomed.2023.04.020.
[29]	Yang Y, Yu L, Zhu T, et al. Neuroprotective effects of Lycium barbarum polysaccharide on light-induced oxidative stress and mitochondrial damage via the Nrf2/HO-1 pathway in mouse hippocampal neurons[J]. Int J Biol Macromol, 2023, 251:126315. doi: 10.1016/j.ijbiomac.2023.126315.
[30]	Wang Z, Sun Q, Fang J, et al. The anti-aging activity of Lycium barbarum polysaccharide extracted by yeast fermentation: In vivo and in vitro studies[J]. Int J Biol Macromol, 2022, 209(Pt B):2032-2041. doi: 10.1016/j.ijbiomac.2022.04.184. pmid: 35500780
[31]	刘莉, 杨红萍, 尹建雯, 等. 姜黄素通过PI3K/AKT信号通路减轻幽门螺杆菌感染小鼠胃黏膜炎症反应及氧化应激[J]. 解剖科学进展, 2024, 30(3):279-282. doi: 10.16695/j.cnki.1006-2947.2024.03.015.
[32]	Ding J, Mei S, Wang K, et al. Curcumin modulates oxidative stress to inhibit pyroptosis and improve the inflammatory microenvironment to treat endometriosis[J]. Genes Dis, 2024, 11(3):101053. doi: 10.1016/j.gendis.2023.06.022.
[33]	Wei H, Fang G, Song W, et al. Resveratrol's bibliometric and visual analysis from 2014 to 2023[J]. Front Plant Sci, 2024, 15:1423323. doi: 10.3389/fpls.2024.1423323.
[34]	Wątroba M, Szukiewicz D. Anti-Inflammatory Properties of Resveratrol[J]. Int J Mol Sci, 2025, 26(23):11710. doi: 10.3390/ijms262311710.
[35]	Gołąbek-Grenda A, Kaczmarek M, Juzwa W, et al. Natural resveratrol analogs differentially target endometriotic cells into apoptosis pathways[J]. Sci Rep, 2023, 13(1):11468. doi: 10.1038/s41598-023-38692-8. pmid: 37454164
[36]	Chen Z, Wang C, Lin C, et al. Lipidomic Alterations and PPARα Activation Induced by Resveratrol Lead to Reduction in Lesion Size in Endometriosis Models[J]. Oxid Med Cell Longev, 2021, 2021:9979953. doi: 10.1155/2021/9979953.
[37]	Cao Y, Tan YJ, Huang D. Molecular Mechanism of 5,6-Dihydroxyflavone in Suppressing LPS-Induced Inflammation and Oxidative Stress[J]. Int J Mol Sci, 2024, 25(19):10694. doi: 10.3390/ijms251910694.
[38]	Yi ZH, Li SQ, Ke JY, et al. Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis[J]. Curr Issues Mol Biol, 2022, 44(12):6189-6204. doi: 10.3390/cimb44120422.
[39]	Ferella L, Bastón JI, Bilotas MA, et al. Active compounds present in Rosmarinus officinalis leaves and Scutellaria baicalensis root evaluated as new therapeutic agents for endometriosis[J]. Reprod Biomed Online, 2018, 37(6):769-782. doi: 10.1016/j.rbmo.2018.09.018.
[40]	Park W, Jang H, Kim HS, et al. Therapeutic efficacy and anti-inflammatory mechanism of baicalein on endometriosis progression in patient-derived cell line and mouse model[J]. Phytomedicine, 2024, 130:155469. doi: 10.1016/j.phymed.2024.155469.