{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:02:54Z","timestamp":1787058174596,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005719","name":"Dicle University Project Research Platform (DUBAP)","doi-asserted-by":"publisher","award":["TIP.22.011"],"award-info":[{"award-number":["TIP.22.011"]}],"id":[{"id":"10.13039\/501100005719","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Objectives: Endometriosis (EM) is the presence of endometrial tissue outside the uterus. This study aimed to examine the effects of quince gel and hesperidin treatment on uterine tissue in an experimental endometriosis model. Materials and Methods: Thirty-two rats were categorized into four groups as sham, EM, EM+quince gel (QG), and EM+QG+Hesperidin (HES). The endometriosis (EM) model was induced with surgical intervention. Estradiol benzoate (EB) was used to induce endometrial hyperplasia. In the EM group, EB was given to rats for 7 days. The EM+QG group received 2 cc QG for 21 days. HES treatment was given for 21 days after EM induction. At the end of the experiment, blood was taken from the animals and the serum total antioxidant status (TAS) and total oxidant status (TOS) values were studied. Uterine tissues were dissected and processed for histological paraffin embedding. Tissues were fixed in 4% glutaraldehyde solution and processed for ultrastructural analysis. Results: After EM, QG and HES treatment significantly increased the TAS and decreased the TOS value. EM caused epithelial and glandular degeneration, thinning of the basal membranes, and vascular dilatation with increased fibrosis and edema. QG+HES restored the pathology and showed protective effects in uterine tissues. Caspase-3 expression was increased in the epithelium, glands, and muscle layers of the EM group. In EM+QG+HES, hesperidin protected cell survival and decreased Caspase-3 expression in uterine tissues. TNF-\u03b1 expression was intense in inflammatory cells and the muscle layer in the EM group. HES reduced inflammation by decreasing the TNF-\u03b1 expression. MAPK expression was increased after EM induction in epithelial, glandular, and inflammatory cells in the EM group. After HES treatment, MAPK expression was mainly negative in cells of uterine tissue in the EM+QG+HES group. Ultrastructurally, in the EM group, organelles were disrupted and dilated and degenerated after EM induction. QG and HES treatment improved cellular organelles. Conclusion: Local vaginal applications can be an alternative treatment method in the endometriosis model via QG+HES treatment promoting cell proliferation and angiogenesis and preventing cell death.<\/jats:p>","DOI":"10.3390\/molecules28165945","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:45:53Z","timestamp":1691498753000},"page":"5945","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Effects of Quince Gel and Hesperidin Mixture on Experimental Endometriosis"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9714-4670","authenticated-orcid":false,"given":"I\u015f\u0131lay Sezen","family":"Ermi\u015f","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Medical Faculty, Harran University, \u015eanl\u0131urfa 63050, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2353-1184","authenticated-orcid":false,"given":"Engin","family":"Deveci","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Dicle University, Diyarbak\u0131r 21280, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6384-9146","authenticated-orcid":false,"given":"F\u0131rat","family":"A\u015f\u0131r","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical Faculty, Dicle University, Diyarbak\u0131r 21280, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"ref_1","first-page":"e28864","article-title":"Endometriosis: A Review of Clinical Diagnosis, Treatment, and Pathogenesis","volume":"14","author":"Chauhan","year":"2022","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s13669-017-0187-1","article-title":"Endometriosis: Epidemiology, Diagnosis and Clinical Management","volume":"6","author":"Parasar","year":"2017","journal-title":"Curr. Obs. Gynecol. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"179515","DOI":"10.1155\/2014\/179515","article-title":"Theories on the pathogenesis of endometriosis","volume":"2014","author":"Sourial","year":"2014","journal-title":"Int. J. Reprod. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"D\u2019Hooghe, T. (2017). Biomarkers for Endometriosis: State of the Art, Springer International Publishing.","DOI":"10.1007\/978-3-319-59856-7"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0301-2115(00)00405-X","article-title":"Theories of endometriosis","volume":"96","author":"Vinatier","year":"2001","journal-title":"Eur. J. Obs. Gynecol. Reprod. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s11154-021-09666-w","article-title":"Hormonal treatments for endometriosis: The endocrine background","volume":"23","author":"Vannuccini","year":"2022","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chantalat, E., Valera, M.C., Vaysse, C., Noirrit, E., Rusidze, M., Weyl, A., Vergriete, K., Buscail, E., Lluel, P., and Fontaine, C. (2020). Estrogen Receptors and Endometriosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082815"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.1021\/jf0502000","article-title":"Antioxidant Activity of the Flavonoid Hesperidin in Chemical and Biological Systems","volume":"53","author":"Wilmsen","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pyrzynska, K. (2022). Hesperidin: A Review on Extraction Methods, Stability and Biological Activities. Nutrients, 14.","DOI":"10.3390\/nu14122387"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/ptr.5256","article-title":"Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: An updated review of their molecular mechanisms and experimental models","volume":"29","author":"Parhiz","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"369","DOI":"10.5115\/acb.19.119","article-title":"Benefits of hesperidin in central nervous system disorders: A review","volume":"52","author":"Kim","year":"2019","journal-title":"Anat. Cell Biol."},{"key":"ref_12","first-page":"399","article-title":"Hesperidin May Protect Gastric Tissue Against Immobilization Stress","volume":"43","author":"Beskisiz","year":"2021","journal-title":"Anal. Quant. Cytopathol. Histopathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1021\/jf040057v","article-title":"Quince (Cydonia oblonga Miller) fruit (pulp, peel, and seed) and Jam: Antioxidant activity","volume":"52","author":"Silva","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1016\/j.fct.2009.03.017","article-title":"Protective effect of quince (Cydonia oblonga Miller) fruit against oxidative hemolysis of human erythrocytes","volume":"47","author":"Silva","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.3390\/molecules28073066","article-title":"Changes in Physicochemical and Bioactive Properties of Quince (Cydonia oblonga Mill.) and Its Products","volume":"28","author":"Najman","year":"2023","journal-title":"Molecules"},{"key":"ref_16","first-page":"1","article-title":"Nutritional Composition, Phytochemistry and Medicinal Use of Quince (Cydonia oblonga Miller) with Emphasis on its Processed and Fortified Food Products","volume":"11","author":"Hanan","year":"2020","journal-title":"J. Food Process. Technol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1021\/jf0203139","article-title":"Phenolic profile of quince fruit (Cydonia oblonga Miller) (pulp and peel)","volume":"50","author":"Silva","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1021\/jf030564x","article-title":"Free amino acid composition of quince (Cydonia oblonga Miller) fruit (pulp and peel) and jam","volume":"52","author":"Silva","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","first-page":"29","article-title":"A review of nutritional value and putative health-effects of quince (Cydonia oblonga Mill.) fruit","volume":"19","author":"Papp","year":"2013","journal-title":"J. Hortic. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1007\/s10600-012-0310-5","article-title":"A new chromone from seeds of Cydonia oblonga","volume":"48","author":"Ghopur","year":"2012","journal-title":"Chem. Nat. Compd."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.ijsu.2014.06.016","article-title":"Wound healing properties of quince seed mucilage: In vivo evaluation in rabbit full-thickness wound model","volume":"12","author":"Tamri","year":"2014","journal-title":"Int. J. Surg."},{"key":"ref_22","first-page":"303","article-title":"Detection of compounds and antibacterial effect of quince (Cydonia oblonga Miller) extracts in vitro and in vivo","volume":"3","author":"Alizadeh","year":"2013","journal-title":"J. Biol. Act. Prod. Nat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.ijbiomac.2019.10.008","article-title":"Quince seed mucilage-based scaffold as a smart biological substrate to mimic mechanobiological behavior of skin and promote fibroblasts proliferation and h-ASCs differentiation into keratinocytes","volume":"142","author":"Sefat","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.foodchem.2017.05.002","article-title":"Structure characterization and antioxidant activity of polysaccharides from Chinese quince seed meal","volume":"234","author":"Wang","year":"2017","journal-title":"Food Chem."},{"key":"ref_25","first-page":"352","article-title":"Antifungal activities of quince seed mucilage hydrogel decorated with essential oils of Nigella sativa, Citrus sinensis and Cinnamon verum","volume":"13","author":"Mirzaii","year":"2021","journal-title":"Iran. J. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Smolarz, B., Szy\u0142\u0142o, K., and Romanowicz, H. (2021). Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature). Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910554"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.1021\/ja00090a032","article-title":"Flavonoids as Antioxidants","volume":"116","author":"Jovanovic","year":"1994","journal-title":"J. Am. Chem. Soc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.3892\/mmr.2020.11561","article-title":"Hesperidin ameliorates liver ischemia\/reperfusion injury via activation of the Akt pathway","volume":"22","author":"Li","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"928","DOI":"10.5114\/aoms.2015.47697","article-title":"Protective effects of hesperidin in experimental testicular ischemia\/reperfusion injury in rats","volume":"12","author":"Celik","year":"2016","journal-title":"Arch. Med. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1093\/humrep\/dei135","article-title":"ESHRE guideline for the diagnosis and treatment of endometriosis","volume":"20","author":"Kennedy","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"151458","DOI":"10.1016\/j.anndiagpath.2019.151458","article-title":"Endometriosis: Three-year histopathological perspective from the largest hospital in Africa","volume":"45","author":"Mashele","year":"2020","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","article-title":"Emerging roles of caspase-3 in apoptosis","volume":"6","author":"Porter","year":"1999","journal-title":"Cell Death Differ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/35037710","article-title":"The biochemistry of apoptosis","volume":"407","author":"Hengartner","year":"2000","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0306-4522(00)00173-1","article-title":"Functional role and therapeutic implications of neuronal caspase-1 and-3 in a mouse model of traumatic spinal cord injury","volume":"99","author":"Li","year":"2000","journal-title":"Neuroscience"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.bbrc.2003.08.045","article-title":"Role of apoptosis-inducing factor in myocardial cell death by ischemia-reperfusion","volume":"309","author":"Kim","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1159\/000489494","article-title":"The Role of Serum Caspase 3 Levels in Prediction of Endometriosis Severity","volume":"83","author":"Kaya","year":"2018","journal-title":"Gynecol. Obs. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1053\/j.gastro.2013.01.056","article-title":"Transforming growth factor-\u03b2 signaling in hepatocytes promotes hepatic fibrosis and carcinogenesis in mice with hepatocyte-specific deletion of TAK1","volume":"144","author":"Yang","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1073\/pnas.0909781107","article-title":"Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis","volume":"107","author":"Inokuchi","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","first-page":"286","article-title":"TNF-alpha serum levels in women with endometriosis: Prospective clinical study","volume":"70","author":"Galo","year":"2005","journal-title":"Ceska Gynekol."},{"key":"ref_40","first-page":"CD008088","article-title":"Anti-TNF-\u03b1 treatment for pelvic pain associated with endometriosis","volume":"28","author":"Lu","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_41","first-page":"153","article-title":"Mitogen-activated protein (MAP) kinase pathways: Regulation and physiological functions","volume":"22","author":"Pearson","year":"2001","journal-title":"Endocr. Rev."},{"key":"ref_42","first-page":"183","article-title":"The Mitogen-Activated Protein Kinase (MAPK) Pathway: Role in Immune Evasion by Trypanosomatids","volume":"7","author":"Diniz","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.3389\/fpls.2018.01387","article-title":"Mitogen-Activated Protein Kinase Cascades in Plant Hormone Signaling","volume":"9","author":"Jagodzik","year":"2018","journal-title":"Front. Plant. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"106","DOI":"10.2174\/1573404813666170306163448","article-title":"Molecular and Cellular Pathogenesis of Endometriosis","volume":"14","author":"Klemmt","year":"2018","journal-title":"Curr. Womens Health Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1159\/000052856","article-title":"Pathogenesis of endometriosis: The role of peritoneal fluid","volume":"47","author":"Koninckx","year":"1999","journal-title":"Gynecol. Obs. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0015-0282(02)03318-6","article-title":"Peritoneal fluid-mediated enhancement of eutopic and ectopic endometrial cell proliferation is dependent on tumor necrosis factor-alpha in women with endometriosis","volume":"78","author":"Braun","year":"2002","journal-title":"Fertil. Steril."},{"key":"ref_47","first-page":"824","article-title":"Tumor necrosis factor-\u03b1 promotes proliferation of endometriotic stromal cells by inducing interleukin-8 gene and protein expression","volume":"85","author":"Iwabe","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/S0015-0282(16)48988-0","article-title":"Studies on the surgical induction of endometriosis in the rat","volume":"44","author":"Vernon","year":"1985","journal-title":"Fertil. Steril."},{"key":"ref_49","first-page":"1487","article-title":"Daidzein alleviated the pathologies in intestinal tissue against ischemia-reperfusion","volume":"27","author":"Durgun","year":"2023","journal-title":"Eur. Rev. Med. Pharm. Sci."},{"key":"ref_50","first-page":"8209","article-title":"Effect of ellagic acid on damage caused by hepatic ischemia reperfusion in rats","volume":"26","author":"Durgun","year":"2022","journal-title":"Eur. Rev. Med. Pharm. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e3465","DOI":"10.21769\/BioProtoc.3465","article-title":"Semi-quantitative Determination of Protein Expression using Immunohistochemistry Staining and Analysis: An Integrated Protocol","volume":"9","author":"Crowe","year":"2019","journal-title":"Bio-Protocol"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/16\/5945\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:28:01Z","timestamp":1760128081000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/16\/5945"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,8]]},"references-count":51,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["molecules28165945"],"URL":"https:\/\/doi.org\/10.3390\/molecules28165945","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,8]]}}}