{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:39:07Z","timestamp":1785800347824,"version":"3.56.0"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We aimed to investigate the potential antidiabetic effects of an ethanol extract derived from the fruit of Malus floribunda (MF) on insulin resistance, oxidative stress, inflammation, and apoptosis associated with diabetes. In our study, diabetes was induced through the administration of a 10% fructose solution and 40 mg\/kg Streptozotocin (STZ). Once diabetes had been induced, metformin (Met) 300 mg\/kg and the MF extract (250 mg\/kg and 500 mg\/kg) were administered orally once daily for 30 days. At the end of the experiment, markers of insulin resistance, oxidative stress, inflammation and apoptosis were evaluated in the serum, muscle and liver tissues of the different groups. The MF extract significantly improved the levels of HOMA-IR, insulin receptor (InR), insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT4)\u2014key components of peripheral insulin resistance associated with type 2 diabetes. Fructose\/streptozotocin induced oxidative stress, inflammation, and apoptosis were mitigated by increasing Nuclear factor erythroid 2-related factor 2 (NRF2) expression, which restored antioxidant levels (Superoxide dismutase (SOD) and Glutathione (GSH)), significantly improved cytokine levels (Tumor necrosis factor alpha (TNF-\u03b1) and Interleukin-1 beta (IL-1\u03b2)), and downregulated apoptotic proteins (caspase-3 and caspase-9). We demonstrated the antidiabetic effect of MF extract using a fructose\/streptozotocin-induced type 2 diabetes model. MF extract shows promise for future use in herbal medicine.<\/jats:p>","DOI":"10.3390\/ijms27125520","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:37:42Z","timestamp":1781879862000},"page":"5520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Malus floribunda Siebold ex Van Houtte Fruit Extract Mitigates Fructose\/Streptozotocin Induced Type 2 Diabetes in Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0659-3084","authenticated-orcid":false,"given":"Muhammed","family":"Yayla","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Selcuk University, Konya 42100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damla","family":"Binnetoglu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Kafkas University, Kars 36100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erdem","family":"Toktay","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Kafkas University, Kars 36100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huseyin Fatih","family":"Gul","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Kafkas University, Kars 36100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakir","family":"Akgun","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Kafkas University, Kars 36100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0735-4229","authenticated-orcid":false,"given":"Sefa","family":"Gozcu","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Erzincan Binali Yildirim University, Erzincan 24100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugur","family":"Ermis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Kafkas University, Kars 36100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengul","family":"Ozdemir Sarikaya","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Kafkas University, Kars 36100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6856-4002","authenticated-orcid":false,"given":"Merve Dolunay","family":"Uyanik","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Kafkas University, Kars 36100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","unstructured":"Freeman, A.M., Acevedo, L.A., and Pennings, N. (2026). Insulin Resistance. StatPearls, StatPearls Publishing."},{"key":"ref_2","unstructured":"Magliano, D.J., and Boyko, E.J. (2021). IDF Diabetes Atlas, International Diabetes Federation. [10th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice, and Erratum, C. (2024). 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024. Diabetes Care, 47, S158\u2013S178 1238.","DOI":"10.2337\/dc24-S009"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"s349","DOI":"10.5530\/ijper.51.3s.45","article-title":"The Investigation of Phytochemical Contains, Antioxidant and Antimicrobial Activities of Malus floribunda Siebold ex Van Houtte From Eastern Turkey","volume":"51","year":"2017","journal-title":"Indian J. Pharm. Educ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"47","DOI":"10.24326\/asphc.2018.5.5","article-title":"Organ\u0131c ac\u0131ds, sugars, phenol\u0131c compounds and ant\u0131ox\u0131dant act\u0131v\u0131ty of malus flor\u0131bunda cocc\u0131nella fru\u0131t, peel and flesh","volume":"17","author":"Coklar","year":"2018","journal-title":"Acta Sci. Pol. Hortorum Cultus"},{"key":"ref_6","unstructured":"Zaimo\u011flu, S. (2004). Inhibitory Effects of Plant Originated Extracts on Bovine Lens Aldose Reductase, ODTU."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sola, I., Poljuha, D., Mikulic-Petkovsek, M., Davosir, D., Pinteric, M., Bilic, J., Veberic, R., Hudina, M., and Rusak, G. (2022). Biopotential of Underutilized Rosaceae Inflorescences: LC-DAD-MS Phytochemical Profiles Associated with Antioxidant, Antidiabetic, Anti-Inflammatory and Antiproliferative Activity In Vitro. Plants, 11.","DOI":"10.3390\/plants11030271"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5198","DOI":"10.1007\/s12010-023-04826-x","article-title":"Phytochemical Content of Malus floribunda: In Vitro and Molecular Docking Studies","volume":"196","author":"Coteli","year":"2024","journal-title":"Appl. Biochem Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wong, K.C., Cao, S., Dong, X., Law, M.C., Chan, T.H., and Wong, M.S. (2017). (-)-Epiafzelechin Protects against Ovariectomy-induced Bone Loss in Adult Mice and Modulate Osteoblastic and Osteoclastic Functions In Vitro. Nutrients, 9.","DOI":"10.3390\/nu9050530"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"112744","DOI":"10.1016\/j.jep.2020.112744","article-title":"Dacryodes edulis (G. Don) H.J. Lam modulates glucose metabolism, cholinergic activities and Nrf2 expression, while suppressing oxidative stress and dyslipidemia in diabetic rats","volume":"255","author":"Erukainure","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1080\/13813455.2021.1921811","article-title":"Securidaca inappendiculata stem extract confers robust antioxidant and antidiabetic effects against high fructose\/streptozotocin induced type 2 diabetes in rats. Exploration of bioactive compounds using UHPLC-ESI-QTOF-MS","volume":"129","author":"Olatunji","year":"2023","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s00418-022-02131-y","article-title":"Combined resveratrol and vitamin D treatment ameliorate inflammation-related liver fibrosis, ER stress, and apoptosis in a high-fructose diet\/streptozotocin-induced T2DM model","volume":"158","author":"Anapali","year":"2022","journal-title":"Histochem Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ulusan, M., Erdogan, M.A., Simsek, O., Gunes, V., and Erbas, O. (2024). Saccharomyces boulardii Mitigates Fructose-Induced Non-Alcoholic Fatty Liver in Rats. Medicina, 60.","DOI":"10.3390\/medicina60101713"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pengnet, S., Sumarithum, P., Phongnu, N., Prommaouan, S., Kantip, N., Phoungpetchara, I., and Malakul, W. (2022). Naringin attenuates fructose-induced NAFLD progression in rats through reducing endogenous triglyceride synthesis and activating the Nrf2\/HO-1 pathway. Front Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1049818"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12924","DOI":"10.1038\/s41598-021-92345-2","article-title":"High fructose and streptozotocin induced diabetic impairments are mitigated by Indirubin-3-hydrazone via downregulation of PKR pathway in Wistar rats","volume":"11","author":"Udumula","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jep.2009.02.039","article-title":"Momordica charantia extract on insulin resistance and the skeletal muscle GLUT4 protein in fructose-fed rats","volume":"123","author":"Shih","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1055\/s-2008-1073162","article-title":"A high-fructose diet impairs Akt and PKCzeta phosphorylation and GLUT4 translocation in rat skeletal muscle","volume":"40","author":"Li","year":"2008","journal-title":"Horm. Metab. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Roy, J.R., Janaki, C.S., Jayaraman, S., Periyasamy, V., Balaji, T., Vijayamalathi, M., and Veeraraghavan, V.P. (2022). Carica papaya Reduces Muscle Insulin Resistance via IR\/GLUT4 Mediated Signaling Mechanisms in High Fat Diet and Streptozotocin-Induced Type-2 Diabetic Rats. Antioxidants, 11.","DOI":"10.3390\/antiox11102081"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e32718","DOI":"10.1371\/journal.pone.0032718","article-title":"Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: A contributor to the beneficial effects of coffee on diabetes","volume":"7","author":"Ong","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/s11655-025-3934-6","article-title":"Isoquercitrin Improves Insulin Resistance by Inhibiting PTP1B-Regulated IRS\/PI3K\/AKT Signaling Pathway","volume":"32","author":"Liu","year":"2026","journal-title":"Chin. J. Integr. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1007\/s10495-015-1128-y","article-title":"Fructose induces mitochondrial dysfunction and triggers apoptosis in skeletal muscle cells by provoking oxidative stress","volume":"20","author":"Jaiswal","year":"2015","journal-title":"Apoptosis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103577","DOI":"10.1016\/j.etap.2020.103577","article-title":"Protocatechuic acid improves hepatic insulin resistance and restores vascular oxidative status in type-2 diabetic rats","volume":"83","author":"Abdelmageed","year":"2021","journal-title":"Env. Toxicol. Pharmacol."},{"key":"ref_23","first-page":"e14142","article-title":"Geraniol ameliorates the progression of high fat-diet\/streptozotocin-induced type 2 diabetes mellitus in rats via regulation of caspase-3, Bcl-2, and Bax expression","volume":"46","author":"Mostafa","year":"2022","journal-title":"J. Food Biochem"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Alshareef, N.S., AlSedairy, S.A., Al-Harbi, L.N., Alshammari, G.M., and Yahya, M.A. (2024). Carthamus tinctorius L. (Safflower) Flower Extract Attenuates Hepatic Injury and Steatosis in a Rat Model of Type 2 Diabetes Mellitus via Nrf2-Dependent Hypoglycemic, Antioxidant, and Hypolipidemic Effects. Antioxidants, 13.","DOI":"10.3390\/antiox13091098"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"114779","DOI":"10.1016\/j.biopha.2023.114779","article-title":"The ameliorative effect of zinc acetate with caffeic acid in the animal model of type 2 diabetes","volume":"163","author":"Matowane","year":"2023","journal-title":"BioMed Pharmacother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"33353","DOI":"10.1021\/acsomega.5c03465","article-title":"Distachionate and Its Nanocomposites Modulate Oxidative Stress, Inflammation, and Diabetes-Related Genes in High-Fructose\/Streptozotocin Model","volume":"10","author":"Raza","year":"2025","journal-title":"ACS Omega"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1007\/s11033-024-09434-4","article-title":"Resveratrol relieves HFD-induced insulin resistance in skeletal muscle tissue through antioxidant capacity enhancement and the Nrf2-Keap1 signaling pathway","volume":"51","author":"Shabani","year":"2024","journal-title":"Mol. Biol. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"94","DOI":"10.4239\/wjd.v3.i5.94","article-title":"Curcumin attenuates Nrf2 signaling defect, oxidative stress in muscle and glucose intolerance in high fat diet-fed mice","volume":"3","author":"He","year":"2012","journal-title":"World J. Diabetes"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1016\/j.yexcr.2013.07.015","article-title":"Nrf2 modulates contractile and metabolic properties of skeletal muscle in streptozotocin-induced diabetic atrophy","volume":"319","author":"Whitman","year":"2013","journal-title":"Exp. Cell Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"18460","DOI":"10.1038\/s41598-025-03526-2","article-title":"MOTS-c mimics exercise to combat diabetic liver fibrosis by targeting Keap1-Nrf2-Smad2\/3","volume":"15","author":"Chen","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e23357","DOI":"10.1002\/jbt.23357","article-title":"Dimethyl fumarate-mediated Nrf2\/ARE pathway activation and glibenclamide-mediated NLRP3 inflammasome cascade inhibition alleviate type II diabetes-associated fatty liver in rats by mitigating oxidative stress and inflammation","volume":"37","author":"Dwivedi","year":"2023","journal-title":"J. Biochem Mol. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s00210-019-01773-5","article-title":"NLRP3 inhibitor glibenclamide attenuates high-fat diet and streptozotocin-induced non-alcoholic fatty liver disease in rat: Studies on oxidative stress, inflammation, DNA damage and insulin signalling pathway","volume":"393","author":"Dwivedi","year":"2020","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2147\/JIR.S110873","article-title":"Curcumin prevents muscle damage by regulating NF-kappaB and Nrf2 pathways and improves performance: An in vivo model","volume":"9","author":"Sahin","year":"2016","journal-title":"J. Inflamm. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1002\/fsn3.3227","article-title":"Alleviative effects of alpha-lipoic acid on muscle atrophy via the modulation of TNF-alpha\/JNK and PI3K\/AKT pathways in high-fat diet and streptozotocin-induced type 2 diabetic rats","volume":"11","author":"Ko","year":"2023","journal-title":"Food Sci. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9340637","DOI":"10.1155\/2016\/9340637","article-title":"Therapeutic Effects of Quercetin on Inflammation, Obesity, and Type 2 Diabetes","volume":"2016","author":"Chen","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ejphar.2015.12.021","article-title":"Rutin ameliorates diabetic neuropathy by lowering plasma glucose and decreasing oxidative stress via Nrf2 signaling pathway in rats","volume":"771","author":"Tian","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2630460","DOI":"10.1080\/10717544.2026.2630460","article-title":"ROS-triggerable dual nanocoated probiotics for inflammatory bowel disease treatment","volume":"33","author":"Sang","year":"2026","journal-title":"Drug Deliv."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Saad, K.M., Elmasry, K., Baban, B., Livingston, M.J., Dong, Z., Abdelmageed, M.E., Abdelaziz, R.R., Suddek, G.M., and Elmarakby, A.A. (2025). Protocatechuic Acid Ameliorates Cisplatin-Induced Inflammation and Apoptosis in Mouse Proximal Tubular Cells. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26094115"},{"key":"ref_39","first-page":"1611","article-title":"Research progress of chlorogenic acid in improving inflammatory diseases","volume":"48","author":"Ling","year":"2023","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4103\/0973-7847.194044","article-title":"Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid","volume":"10","author":"Arulmoli","year":"2016","journal-title":"Pharmacogn. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bernatoniene, J., and Kopustinskiene, D.M. (2018). The Role of Catechins in Cellular Responses to Oxidative Stress. Molecules, 23.","DOI":"10.3390\/molecules23040965"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Saha, S., Buttari, B., Panieri, E., Profumo, E., and Saso, L. (2020). An Overview of Nrf2 Signaling Pathway and Its Role in Inflammation. Molecules, 25.","DOI":"10.3390\/molecules25225474"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s11033-024-09805-x","article-title":"Hepatoprotective potential of taxifolin in type 2 diabetic rats: Modulation of oxidative stress and Bcl2\/Bax\/Caspase-3 signaling pathway","volume":"51","author":"Khadrawy","year":"2024","journal-title":"Mol. Biol. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s40200-025-01723-4","article-title":"A comparative study to assess two doses of a novel aldose reductase inhibitor (ARI)\/Antioxidant drug candidate Cemtirestat, the current ARI drug Epalrestat, and the antioxidant Stobadine on Fructose- and Streptozotocin-Induced hepatic and pancreatic stress responses in rats","volume":"24","author":"Dagistanli","year":"2025","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"103982","DOI":"10.1016\/j.etap.2022.103982","article-title":"Antioxidant and antiapoptotic effects of quercetin against ochratoxin A-induced nephrotoxicity in broiler chickens","volume":"96","author":"Abdelrahman","year":"2022","journal-title":"Env. Toxicol. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s00403-019-01898-w","article-title":"Rutin and ascorbic acid cooperation in antioxidant and antiapoptotic effect on human skin keratinocytes and fibroblasts exposed to UVA and UVB radiation","volume":"311","author":"Gegotek","year":"2019","journal-title":"Arch. Dermatol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Albrakati, A. (2025). Protective effects of shikimic acid against thioacetamide-induced hepatic fibrosis: Role of Nrf2\/NF-kappaB signaling pathways. Front Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1609711"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e70067","DOI":"10.1111\/1440-1681.70067","article-title":"Chlorogenic Acid Improves Salicylic Acid-Induced Cochlear Injury by Reducing Oxidative Stress and Inflammatory Response Through TLR4\/NF-kappaB Signalling Pathway","volume":"52","author":"Lin","year":"2025","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.2337\/db10-1461","article-title":"Cyanidin-3-O-beta-glucoside and protocatechuic acid exert insulin-like effects by upregulating PPARgamma activity in human omental adipocytes","volume":"60","author":"Scazzocchio","year":"2011","journal-title":"Diabetes"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1039\/C9FO02398D","article-title":"Protective effect of ferulic acid on STZ-induced diabetic nephropathy in rats","volume":"11","author":"Qi","year":"2020","journal-title":"Food Funct."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/13813455.2021.1988981","article-title":"Vanillin improves glucose homeostasis and modulates metabolic activities linked to type 2 diabetes in fructose-streptozotocin induced diabetic rats","volume":"130","author":"Salau","year":"2024","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1016\/j.ijbiomac.2019.10.270","article-title":"Synergistic effect of novel chitosan combined metformin drug on streptozotocin-induced diabetes mellitus rat","volume":"153","author":"Arun","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_53","first-page":"1715","article-title":"Comparison of the therapeutic effects of sacubitril and valsartan combination versus metformin in experimentally induced polycystic ovary syndrome in rats","volume":"28","author":"Yayla","year":"2025","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_56","first-page":"315","article-title":"The effect of specific therapeutic agents on inflammation in sepsis-induced neonatal rats","volume":"45","author":"Ilhan","year":"2020","journal-title":"Turk. Biyokim Derg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"632","DOI":"10.17826\/cumj.871862","article-title":"Neuroprotective effects of phloretin and phloridzin on paclitaxel-induced neuronal damage in primary neuron cells","volume":"46","author":"Yayla","year":"2021","journal-title":"Cukurova Med. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"106050","DOI":"10.1016\/j.tiv.2025.106050","article-title":"Effect of serotonin 7 receptors and transcript variants on RIN-5F pancreatic beta cell line","volume":"106","author":"Yayla","year":"2025","journal-title":"Toxicol. Vitr."},{"key":"ref_59","first-page":"508","article-title":"Effects of fisetin to letrozole-induced polycystic ovary syndrome in rats","volume":"2","author":"Toktay","year":"2021","journal-title":"Cukurova Med. J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5520\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:39:36Z","timestamp":1781879976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5520"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":59,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125520"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125520","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]}}}