{"paper_id":"a5c5353c-bcdb-442d-98d2-62a6c5003391","body_text":"Abstract\nWe studied the effect nanomicelle curcumin on oxidative stress markers, pro-inflammatory cytokines, and assisted reproductive techniques (ART) outcomes in endometriosis cases. This randomized controlled trial was conducted on 50 women with endometriosis at the age of 25–35 candidate for ART referred to Roya Infertility Center in Qom, Iran, 2022. The participants were allocated to intervention (n = 25) and control (n = 25) groups by the blocked randomization method. Nanomicelle curcumin with a dose of 120 mg per day was given to the intervention group twice a day for 10 weeks, and the placebo with the same dose was given to the control group. Follicular fluid (FF) samples were collected from women with endometriosis stage III/IV undergoing ART. Antioxidant enzyme (MDA, SOD, CAT, and TAC) and pro-inflammatory cytokines (IL-8 and TNF-a) were tested. ART results such as (number of oocyte received, high-quality embryo, and pregnancy outcomes) were compared between two groups. Increased serum levels of TAC, CAT, and SOD were observed after nanomicelle curcumin treatment. Furthermore, FF levels of MDA, IL-8, and TNF-a reduced significantly after treatment in nanomicelle curcumin. Nanomicelle curcumin supplementation led to an improved number of oocytes retrieved, number of mature (MII) oocytes, fertilization, cleavage, and high-quality embryos. Nanomicelle curcumin treatment can modulate stress oxidative and inflammation in endometriosis-induced infertile patients. ART outcomes also improved after nanomicelle curcumin therapy. Our results suggest that nanomicelle curcumin can be a therapeutic target for infertile patients with endometriosis.\nSimilar content being viewed by others\nData availability\nAll source data for this work (or generated in this study) are available upon reasonable request.\nCode availability\nNot applicable.\nReferences\nAftab N, Vieira A (2010) Antioxidant activities of curcumin and combinations of this curcuminoid with other phytochemicals. Phytother Res 24(4):500–502\nAggarwal BB, Gupta SC, Sung B (2013) Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers. Br J Pharmacol 169(8):1672–1692\nAlabdali A et al (2021) Antioxidant activity of Curcumin. Res J Pharm Technol 14(12):6741–6746\nAlaee S et al (2024) Curcumin mitigates acrylamide-induced ovarian antioxidant disruption and apoptosis in female Balb/c mice: A comprehensive study on gene and protein expressions. Food Sci Nutr 12(6):4160–4172\nAltun T et al (2011) Low follicular fluid IL-6 levels in IVF patients are associated with increased likelihood of clinical pregnancy. J Assist Reprod Genet 28:245–251\nAnjum S et al (2021) Emerging applications of nanotechnology in healthcare systems: Grand challenges and perspectives. Pharmaceuticals 14(8):707\nArafah M, Rashid S, Akhtar M (2021) Endometriosis: a comprehensive review. Adv Anat Pathol 28(1):30–43\nBaboo KD, Chen Z-Y, Zhang X-M (2019) Role of oxidative stress and antioxidant therapies in endometriosis. Reprod Dev Med 3(03):170–176\nBedaiwy M et al (2007) Differential expression of follicular fluid cytokines: relationship to subsequent pregnancy in IVF cycles. Reprod Biomed Online 15(3):321–325\nCai L et al (2020) Accurate detection of β-hCG in women’s serum and cervical secretions for predicting early pregnancy viability based on time-resolved luminescent lanthanide nanoprobes. Nanoscale 12(12):6729–6735\nCanis M et al (1997) Revised american society for reproductive medicine classification of endometriosis: 1996. Fertil Steril 67(5):817–821\nDa Broi M et al (2018) Influence of follicular fluid and cumulus cells on oocyte quality: clinical implications. J Assist Reprod Genet 35:735–751\nDonnez J, Cacciottola L (2022) Endometriosis: an inflammatory disease that requires new therapeutic options. Int J Mol Sci 23(3):1518. https://doi.org/10.3390/ijms23031518\nFernández-Lázaro D et al (2020) Modulation of exercise-induced muscle damage, inflammation, and oxidative markers by curcumin supplementation in a physically active population: a systematic review. Nutrients 12(2):501\nFu Y-S et al (2021) Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential. Biomed Pharmacother 141:111888\nFuloria S et al (2022) A comprehensive review on the therapeutic potential of Curcuma longa Linn. in relation to its major active constituent curcumin. Front Pharmacol 13:820806\nGarzon S et al (2021) Novel drug delivery methods for improving efficacy of endometriosis treatments. Expert Opin Drug Deliv 18(3):355–367\nGhanbarzadeh-Ghashti N et al (2023) The effect of Curcumin on metabolic parameters and androgen level in women with polycystic ovary syndrome: a randomized controlled trial. BMC Endocr Disord 23(1):40\nGudarzi R et al (2024) Effect of curcumin on painful symptoms of endometriosis: A triple-blind randomized controlled trial. Phytother Res 38(1):147–155\nGupta S, Harlev A, Agarwal A (2015) Endometriosis: a comprehensive update. vol 285. Springer, Cham\nHaleem A et al (2023) Applications of nanotechnology in medical field: a brief review. Glob Health J 7(2):70–77\nHeshmati J et al (2021) Effects of curcumin supplementation on blood glucose, insulin resistance and androgens in patients with polycystic ovary syndrome: A randomized double-blind placebo-controlled clinical trial. Phytomedicine 80:153395\nJamilian M et al (2020) Effects of curcumin on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Clin Nutr ESPEN 36:128–133\nJana SK et al (2010) Upper control limit of reactive oxygen species in follicular fluid beyond which viable embryo formation is not favorable. Reprod Toxicol 29(4):447–451\nJyotirmayee B, Mahalik G (2022) A review on selected pharmacological activities of Curcuma longa L. Int J Food Prop 25(1):1377–1398\nKajihara H et al (2011) New insights into the pathophysiology of endometriosis: from chronic inflammation to danger signal. Gynecol Endocrinol 27(2):73–79\nKalaitzopoulos DR et al (2021) Treatment of endometriosis: a review with comparison of 8 guidelines. BMC Womens Health 21:1–9\nKumar A et al (2021) Current clinical developments in curcumin-based therapeutics for cancer and chronic diseases. Phytother Res 35(12):6768–6801\nLee KS et al (2000) Relationships between concentrations of tumor necrosis factor-α and nitric oxide in follicular fluid and oocyte quality. J Assist Reprod Genet 17:222–228\nLee S-B et al (2018) Kaempferol 7-O-β-D-glucoside isolated from the leaves of Cudrania tricuspidata inhibits LPS-induced expression of pro-inflammatory mediators through inactivation of NF-κB, AP-1, and JAK-STAT in RAW 264.7 macrophages. Chem Biol Interact 284:101–111\nLin Y-H et al (2018) Chronic niche inflammation in endometriosis-associated infertility: current understanding and future therapeutic strategies. Int J Mol Sci 19(8):2385\nMáté G, Bernstein LR, Török AL (2018) Endometriosis is a cause of infertility. Does reactive oxygen damage to gametes and embryos play a key role in the pathogenesis of infertility caused by endometriosis? Front Endocrinol 9:419855\nPanieri E et al (2020) Potential applications of NRF2 modulators in cancer therapy. Antioxidants 9(3):193\nPasqualotto EB et al (2004) Effect of oxidative stress in follicular fluid on the outcome of assisted reproductive procedures. Fertil Steril 81(4):973–976\nRestrepo-Osorio J et al (2020) Determination of nutritional value of turmeric flour and the antioxidant activity of Curcuma longa rhizome extracts from agroecological and conventional crops of Valle del Cauca-Colombia. Rev Colomb Quím 49(1):26–32\nRobertson SA et al (2018) Embryotoxic cytokines—potential roles in embryo loss and fetal programming. J Reprod Immunol 125:80–88\nScazzocchio B, Minghetti L, D’Archivio M (2020) Interaction between gut microbiota and curcumin: a new key of understanding for the health effects of curcumin. Nutrients 12(9):2499\nScott L et al (2000) The morphology of human pronuclear embryos is positively related to blastocyst development and implantation. Hum Reprod 15(11):2394–2403\nSingh AK et al (2013) Markers of oxidative stress in follicular fluid of women with endometriosis and tubal infertility undergoing IVF. Reprod Toxicol 42:116–124\nSingh A et al (2022) Therapeutic potential of curcumin in endometrial disorders: Current status and future perspectives. Drug Discov Today 27(3):900–911\nSrushti S et al (2023) Role of activator protein-1 transcription factor in oral cancer. Curr Cancer Ther Rev 19(2):103–116\nTalib WH et al (2022) Combination anticancer therapies using selected phytochemicals. Molecules 27(17):5452\nTaylor HS, Kotlyar AM, Flores VA (2021) Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet 397(10276):839–852\nUllah A et al (2023) CXC chemokines influence immune surveillance in immunological disorders: Polycystic ovary syndrome and endometriosis. Biochim Biophys Acta (BBA) Mol Basis Dis, pp 166704\nVahid F et al (2023) Pro-and antioxidant effect of food items and matrices during simulated in vitro digestion. Foods 12(8):1719\nVallée A, Lecarpentier Y (2020) Curcumin and endometriosis. Int J Mol Sci 21(7):2440. https://doi.org/10.3390/ijms21072440\nVasanthkumar T, Hanumanthappa M, Lakshminarayana R (2019) Curcumin and capsaicin modulates LPS induced expression of COX-2, IL-6 and TGF-β in human peripheral blood mononuclear cells. Cytotechnology 71:963–976\nXu Y, Liu L (2017) Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF-κB signaling pathway. Influenza Other Respir Viruses 11(5):457–463\nYland J et al (2020) Endometrioma, the follicular fluid inflammatory network and its association with oocyte and embryo characteristics. Reprod Biomed Online 40(3):399–408\nAcknowledgements\nThis study was supported by IVF Unit of Infertility, and Research Center of the ACECR, Qom.\nFunding\nNo funding.\nAuthor information\nAuthors and Affiliations\nContributions\nR. Jannatifar, E, Cheraghi, and A. Verdi, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing – original draft. E. Asa: Data curation, and Writing –editing. The authors declare that all data were generated in-house and that no paper mill was used.\nCorresponding author\nEthics declarations\nHuman ethics\nIR.ACECR.JDM.REC.1400.081 and IRCT20170923036334N4\nConsent to participate\nNot applicable.\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nAdditional information\nPublisher's Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nJannatifar, R., Asa, E., Cheraghi, E. et al. Nanomicelle curcumin improves oxidative stress, inflammatory markers, and assisted reproductive techniques outcomes in endometriosis cases: a randomized clinical trial. Naunyn-Schmiedeberg's Arch Pharmacol 398, 11933–11941 (2025). https://doi.org/10.1007/s00210-025-03958-7\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s00210-025-03958-7","source_license":"CC0","license_restricted":false}