{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T01:22:57Z","timestamp":1775179377856,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["122020900136\u20134"],"award-info":[{"award-number":["122020900136\u20134"]}]},{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["ED431C2018\/05"],"award-info":[{"award-number":["ED431C2018\/05"]}]},{"name":"Institute of Immunology and Physiology UB Russian Academy of Science (IIP UB RAS)","award":["122020900136\u20134"],"award-info":[{"award-number":["122020900136\u20134"]}]},{"name":"Institute of Immunology and Physiology UB Russian Academy of Science (IIP UB RAS)","award":["ED431C2018\/05"],"award-info":[{"award-number":["ED431C2018\/05"]}]},{"name":"European Regional European Funds","award":["122020900136\u20134"],"award-info":[{"award-number":["122020900136\u20134"]}]},{"name":"European Regional European Funds","award":["ED431C2018\/05"],"award-info":[{"award-number":["ED431C2018\/05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 2 diabetes is characterized by hyperglycemia and a relative loss of \u03b2\u2013cell function. Our research investigated the antidiabetic potential of betulin, a pentacyclic triterpenoid found primarily in birch bark and, intriguingly, in a few marine organisms. Betulin has been shown to possess diverse biological activities, including antioxidant and antidiabetic activities; however, no studies have fully explored the effects of betulin on the pancreas and pancreatic islets. In this study, we investigated the effect of betulin on streptozotocin\u2013nicotinamide (STZ)-induced diabetes in female Wistar rats. Betulin was prepared as an emulsion, and intragastric treatments were administered at doses of 20 and 50 mg\/kg for 28 days. The effect of treatment was assessed by analyzing glucose parameters such as fasting blood glucose, hemoglobin A1C, and glucose tolerance; hepatic and renal biomarkers; lipid peroxidation; antioxidant enzymes; immunohistochemical analysis; and hematological indices. Administration of betulin improved the glycemic response and decreased \u03b1\u2013amylase activity in diabetic rats, although insulin levels and homeostatic model assessment for insulin resistance (HOMA\u2013IR) scores remained unchanged. Furthermore, betulin lowered the levels of hepatic biomarkers (aspartate aminotransferase, alanine aminotransferase, and alpha-amylase activities) and renal biomarkers (urea and creatine), in addition to improving glutathione levels and preventing the elevation of lipid peroxidation in diabetic animals. We also found that betulin promoted the regeneration of \u03b2\u2013cells in a dose-dependent manner but did not have toxic effects on the pancreas. In conclusion, betulin at a dose of 50 mg\/kg exerts a pronounced protective effect against cytolysis, diabetic nephropathy, and damage to the acinar pancreas and may be a potential treatment option for diabetes.<\/jats:p>","DOI":"10.3390\/ijms25042166","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T04:47:45Z","timestamp":1707713265000},"page":"2166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Protective Effect of Betulin on Streptozotocin\u2013Nicotinamide-Induced Diabetes in Female Rats"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-0825","authenticated-orcid":false,"given":"Feyisayo O.","family":"Adepoju","sequence":"first","affiliation":[{"name":"Department of Technology for Organic Synthesis, Institute of Chemical Technology, Ural Federal University, Mira 19, 620002 Yekaterinburg, Russia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7024-4110","authenticated-orcid":false,"given":"Ksenia V.","family":"Sokolova","sequence":"additional","affiliation":[{"name":"Department of Technology for Organic Synthesis, Institute of Chemical Technology, Ural Federal University, Mira 19, 620002 Yekaterinburg, Russia"},{"name":"Institute of Immunology and Physiology, Russian Academy of Sciences, 620049 Yekaterinburg, Russia"}]},{"given":"Irina F.","family":"Gette","sequence":"additional","affiliation":[{"name":"Department of Technology for Organic Synthesis, Institute of Chemical Technology, Ural Federal University, Mira 19, 620002 Yekaterinburg, Russia"},{"name":"Institute of Immunology and Physiology, Russian Academy of Sciences, 620049 Yekaterinburg, Russia"}]},{"given":"Irina G.","family":"Danilova","sequence":"additional","affiliation":[{"name":"Department of Technology for Organic Synthesis, Institute of Chemical Technology, Ural Federal University, Mira 19, 620002 Yekaterinburg, Russia"},{"name":"Institute of Immunology and Physiology, Russian Academy of Sciences, 620049 Yekaterinburg, Russia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-3890","authenticated-orcid":false,"given":"Mikhail V.","family":"Tsurkan","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Polymer Research, 01069 Dresden, Germany"}]},{"given":"Alicia C.","family":"Mondragon","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Anal\u00edtica, Nutrici\u00f3n y Bromatolog\u00eda, Campus Terra, Universidade da Santiago de Compostela, 27002 Lugo, Spain"}]},{"given":"Elena G.","family":"Kovaleva","sequence":"additional","affiliation":[{"name":"Department of Technology for Organic Synthesis, Institute of Chemical Technology, Ural Federal University, Mira 19, 620002 Yekaterinburg, Russia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7992-1491","authenticated-orcid":false,"given":"Jose Manuel","family":"Miranda","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Anal\u00edtica, Nutrici\u00f3n y Bromatolog\u00eda, Campus Terra, Universidade da Santiago de Compostela, 27002 Lugo, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,10]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Federation (2021). IDF Diabetes Atlas 2021, IDF Diabetes Atlas."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1258\/ebm.2012.011372","article-title":"Streptozotocin-Nicotinamide-Induced Diabetes in the Rat. Characteristics of the Experimental Model","volume":"237","author":"Szkudelski","year":"2012","journal-title":"Exp. Biol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1590\/s2175-97902018000217171","article-title":"Anti-Diabetic Effect of Betulinic Acid on Streptozotocin- Nicotinamide Induced Diabetic Male Mouse Model","volume":"54","author":"Birgani","year":"2018","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"103922","DOI":"10.1016\/j.jff.2020.103922","article-title":"Anti-Diabetic Effect of Isoflavone Rich Kudzu Root Extract in Experimentally Induced Diabetic Rats","volume":"68","author":"Duru","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Najafian, M. The Effects of Curcumin on Alpha Amylase in Diabetics Rats. Zahedan J. Res. Med. Sci., 2015. in press.","DOI":"10.17795\/zjrms-5198"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s11101-014-9369-x","article-title":"The Role of Triterpenes in the Management of Diabetes Mellitus and Its Complications","volume":"14","author":"Nazaruk","year":"2015","journal-title":"Phytochem. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.chembiol.2008.01.013","article-title":"Antidiabetic Activities of Triterpenoids Isolated from Bitter Melon Associated with Activation of the AMPK Pathway","volume":"15","author":"Tan","year":"2008","journal-title":"Chem. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.sajb.2023.10.067","article-title":"In Vitro Evaluation of the Anticancer Potential of Betulin, Isolated from the Seaweed Sargassum Ilicifolium, against Hep-2, THP-1 and HeLa Cell Lines","volume":"163","author":"Perumal","year":"2023","journal-title":"S. Afr. J. Bot."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"34","DOI":"10.7324\/JAPS.2016.60306","article-title":"Bioactive Betulin Produced by Marine Paecilomyces WE3-F","volume":"6","author":"Barakat","year":"2016","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Adepoju, F.O., Duru, K.C., Li, E., Kovaleva, E.G., and Tsurkan, M.V. (2023). Pharmacological Potential of Betulin as a Multitarget Compound. Biomolecules, 13.","DOI":"10.3390\/biom13071105"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1007\/s10753-020-01405-8","article-title":"Betulin Alleviates Myocardial Ischemia\u2013Reperfusion Injury in Rats via Regulating the Siti1\/NLRP3\/NF-\u03baB Signaling Pathway","volume":"44","author":"Yu","year":"2021","journal-title":"Inflammation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"106653","DOI":"10.1016\/j.intimp.2020.106653","article-title":"Betulin Alleviates on Myocardial Inflammation in Diabetes Mice via Regulating Siti1\/NLRP3\/NF-\u03baB Pathway","volume":"85","author":"Wen","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"54","DOI":"10.32792\/utq\/utjsci\/v6i1.45","article-title":"Hussien. Isolation, Purification and Identification of Active Chemical Compound Lup-20(29)-Ene-3, 28-Diol (Betulin) from Tetradium Daniellii Leaves and Study the Hypoglycemic Effect on Rabbits","volume":"6","author":"Alsaadi","year":"2016","journal-title":"Univ. Thi-Qar J. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.cmet.2010.12.004","article-title":"Inhibition of SREBP by a Small Molecule, Betulin, Improves Hyperlipidemia and Insulin Resistance and Reduces Atherosclerotic Plaques","volume":"13","author":"Tang","year":"2011","journal-title":"Cell Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s13340-015-0212-4","article-title":"Glucose Area under the Curve during Oral Glucose Tolerance Test as an Index of Glucose Intolerance","volume":"7","author":"Sakaguchi","year":"2016","journal-title":"Diabetol. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"224","DOI":"10.2337\/diab.47.2.224","article-title":"Experimental NIDDM: Development of a New Model in Adult Rats Administered Streptozotocin and Nicotinamide","volume":"47","author":"Masiello","year":"1998","journal-title":"Diabetes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/jcla.1860070510","article-title":"Review of Diabetes: Identification of Markers for Early Detection, Glycemic Control, and Monitoring Clinical Complications","volume":"7","author":"Wu","year":"1993","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Poovitha, S., and Parani, M. (2016). In Vitro and in Vivo \u03b1-Amylase and \u03b1-Glucosidase Inhibiting Activities of the Protein Extracts from Two Varieties of Bitter Gourd (Momordica charantia L.). BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1085-1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7836823","DOI":"10.1155\/2016\/7836823","article-title":"A 70% Ethanol Extract of Mistletoe Rich in Betulin, Betulinic Acid, and Oleanolic Acid Potentiated \u03b2-Cell Function and Mass and Enhanced Hepatic Insulin Sensitivity","volume":"2016","author":"Ko","year":"2016","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3109\/10717544.2014.881438","article-title":"Preparation and Characterization of Betulin Nanoparticles for Oral Hypoglycemic Drug by Antisolvent Precipitation","volume":"21","author":"Zhao","year":"2014","journal-title":"Drug Deliv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.neuro.2016.09.009","article-title":"Protective Effect of Betulin on Cognitive Decline in Streptozotocin (STZ)-Induced Diabetic Rats","volume":"57","author":"Ma","year":"2016","journal-title":"Neurotoxicology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ratna Wulan, D., Priyo Utomo, E., and Mahdi, C. (2015). Antidiabetic Activity of Ruellia tuberosa L., Role of \u03b1-Amylase Inhibitor: In Silico, In Vitro, and In Vivo Approaches. Biochem. Res. Int., 2015.","DOI":"10.1155\/2015\/349261"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2337\/diaclin.23.3.115","article-title":"Elevated Liver Function Tests in Type 2 Diabetes","volume":"23","author":"Harris","year":"2005","journal-title":"Clin. Diabetes"},{"key":"ref_24","first-page":"e3626","article-title":"Elevated Liver Enzymes in Patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease","volume":"10","author":"Mandal","year":"2018","journal-title":"Cureus"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"142","DOI":"10.4103\/1735-5362.223796","article-title":"The Effect of Betulinic Acid on Leptin, Adiponectin, Hepatic Enzyme Levels and Lipid Profiles in Streptozotocin-Nicotinamide-Induced Diabetic Mice","volume":"13","author":"Ahangarpour","year":"2018","journal-title":"Res. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"F518","DOI":"10.1152\/ajprenal.00656.2020","article-title":"A Plasma Creatinine- And Urea-Based Equation to Estimate Glomerular Filtration Rate in Rats","volume":"320","author":"Besseling","year":"2021","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez, F. (2021). Glycolysis and Gluconeogenesis: A Teaching View. J. Biol. Chem., 296.","DOI":"10.1016\/j.jbc.2020.100016"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"881231","DOI":"10.3389\/fphar.2022.881231","article-title":"Hepatoprotective Effects of Glycyrrhetinic Acid on Lithocholic Acid-Induced Cholestatic Liver Injury Through Choleretic and Anti-Inflammatory Mechanisms","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3390\/biom5010194","article-title":"Advanced Glycation End Products and Oxidative Stress in Type 2 Diabetes Mellitus","volume":"5","author":"Nowotny","year":"2015","journal-title":"Biomolecules"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"959011","DOI":"10.3389\/fendo.2022.959011","article-title":"Latent Autoimmune Diabetes in Adults: A Focus on \u03b2-Cell Protection and Therapy","volume":"13","author":"Yin","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1111\/jdi.13576","article-title":"\u03b2-Cell Failure in Diabetes: Common Susceptibility and Mechanisms Shared between Type 1 and Type 2 Diabetes","volume":"12","author":"Ikegami","year":"2021","journal-title":"J. Diabetes Investig."},{"key":"ref_32","first-page":"110","article-title":"Islet Pathology and the Pathogenesis of Type 1 and Type 2 Diabetes Mellitus Revisited","volume":"4","author":"Habich","year":"1985","journal-title":"Surv. Synth. Pathol. Res."},{"key":"ref_33","first-page":"203","article-title":"Betulinic Acid Reduces the Complications of Autoimmune Diabetes on the Body and Kidney through Effecting on Inflammatory Cytokines in C57BL\/6 Mice","volume":"12","author":"Khataylou","year":"2021","journal-title":"Vet. Res. Forum"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.lfs.2015.12.003","article-title":"Betulin Attenuates Kidney Injury in Septic Rats through Inhibiting TLR4\/NF-\u03baB Signaling Pathway","volume":"144","author":"Zhao","year":"2016","journal-title":"Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"841818","DOI":"10.3389\/fphar.2022.841818","article-title":"Antioxidant and Anti-Inflammatory Properties of Resveratrol in Diabetic Nephropathy: A Systematic Review and Meta-Analysis of Animal Studies","volume":"13","author":"Hu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1111\/1750-3841.14505","article-title":"Lycopene Ameliorated Oxidative Stress and Inflammation in Type 2 Diabetic Rats","volume":"84","author":"Zheng","year":"2019","journal-title":"J. Food Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1556\/2060.106.2019.26","article-title":"Betulin Attenuated Liver Damage by Prevention of Hepatic Mitochondrial Dysfunction in Rats with Alcoholic Steatohepatitis","volume":"106","author":"Buko","year":"2019","journal-title":"Physiol. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1093\/jpp\/rgab015","article-title":"Triterpenoid Compound Betulin Attenuates Allergic Airway Inflammation by Modulating Antioxidants, Inflammatory Cytokines and Tissue Transglutaminase in Ovalbumin-Induced Asthma Mice Model","volume":"73","author":"Kamaraj","year":"2021","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kruszniewska-Rajs, C., Strza\u0142ka-Mrozik, B., Kimsa-Dudek, M., Synowiec-Wojtarowicz, A., Chrobak, E., B\u0119benek, E., Boryczka, S., G\u0142uszek, S., and Gola, J.M. (2022). The Influence of Betulin and Its Derivatives EB5 and ECH147 on the Antioxidant Status of Human Renal Proximal Tubule Epithelial Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052524"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhang, W., Jiang, H., Yang, J., Jin, M., Du, Y., Sun, Q., Cao, L., and Xu, H. (2019). Safety Assessment and Antioxidant Evaluation of Betulin by LC-MS Combined with Free Radical Assays. Anal. Biochem., 587.","DOI":"10.1016\/j.ab.2019.113460"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Arkew, M., Yemane, T., Mengistu, Y., Gemechu, K., and Tesfaye, G. (2021). Hematological Parameters of Type 2 Diabetic Adult Patients at Debre Berhan Referral Hospital, Northeast Ethiopia: A Comparative Cross-Sectional Study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0253286"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"62","DOI":"10.2174\/1573399814666180119143026","article-title":"Correlation Between White Blood Cell Count and Insulin Resistance in Type 2 Diabetes","volume":"15","author":"Mahdiani","year":"2018","journal-title":"Curr. Diabetes Rev."},{"key":"ref_43","unstructured":"Shin, A., Connolly, S., and Kabytaev, K. (2023). Advances in Clinical Chemistry, Elsevier."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"276","DOI":"10.2337\/dc11-2298","article-title":"White Blood Cells Count and Incidence of Type 2 Diabetes in Young Men","volume":"36","author":"Twig","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1590\/S1519-69842009000200026","article-title":"Biological Indicators of Stress in Pacu (Piaractus mesopotamicus) after Capture","volume":"69","author":"Abreu","year":"2009","journal-title":"Braz. J. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0165-1781(98)00059-6","article-title":"Influence of Academic Examination Stress on Hematological Measurements in Subjectively Healthy Volunteers","volume":"80","author":"Maes","year":"1998","journal-title":"Psychiatry Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"G\u00fcnther, A., Makuch, E., Nowak, A., Duchnik, W., Kucharski, \u0141., Pe\u0142ech, R., and Klimowicz, A. (2021). Enhancement of the Antioxidant and Skin Permeation Properties of Betulin and Its Derivatives. Molecules, 26.","DOI":"10.3390\/molecules26113435"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5065","DOI":"10.1016\/j.bmcl.2017.09.027","article-title":"sheng Pentacyclic Triterpenes as \u03b1-Glucosidase and \u03b1-Amylase Inhibitors: Structure-Activity Relationships and the Synergism with Acarbose","volume":"27","author":"Zhang","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Amiri, S., Dastghaib, S., Ahmadi, M., Mehrbod, P., Khadem, F., Behrouj, H., Aghanoori, M.R., Machaj, F., Ghamsari, M., and Rosik, J. (2020). Betulin and Its Derivatives as Novel Compounds with Different Pharmacological Effects. Biotechnol. Adv., 38.","DOI":"10.1016\/j.biotechadv.2019.06.008"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"082017","DOI":"10.1088\/1755-1315\/548\/8\/082017","article-title":"Betulin Nanosuspension as a Promising Raw Material for the Production of Long-Term Storage Bread","volume":"548","author":"Zavorokhina","year":"2020","journal-title":"IOP Conf. Ser. Earth Environ. Sci."},{"key":"ref_51","unstructured":"(2023, December 09). EUR-Lex-32010L006-EN -EUR-Lex. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=celex%3A32010L0063."},{"key":"ref_52","first-page":"795","article-title":"Hypoglycemic Effect of Betulin in Rats with Experimental Diabetes","volume":"80","author":"Zakrzeska","year":"2023","journal-title":"Acta Pol. Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.biopha.2017.07.117","article-title":"Partial Recovery from Alloxan-Induced Diabetes by Sodium Phthalhydrazide in Rats","volume":"95","author":"Danilova","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1111\/cen.13443","article-title":"Area under the Curve during OGTT in First-Degree Relatives of Diabetic Patients as an Efficient Indicator of Future Risk of Type 2 Diabetes and Prediabetes","volume":"87","author":"Feizi","year":"2017","journal-title":"Clin. Endocrinol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis Model Assessment: Insulin Resistance and \u03b2-Cell Function from Fasting Plasma Glucose and Insulin Concentrations in Man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/BF02894268","article-title":"Superoxide Dismutase and Catalase Activities and Their Correlation with Malondialdehyde in Schizophrenic Patients","volume":"19","author":"Rukmini","year":"2004","journal-title":"Indian J. Clin. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/0003-2697(71)90370-8","article-title":"Superoxide Dismutase: Improved Assays and an Assay Applicable to Acrylamide Gels","volume":"44","author":"Beauchamp","year":"1971","journal-title":"Anal. Biochem."},{"key":"ref_58","first-page":"223","article-title":"Colorimetric Method for Determining SH Groups and SS Bonds in Proteins Using 5, 5-Dithiobis (2-Nitrobenzoic) Acid","volume":"1","author":"Verevkina","year":"1977","journal-title":"Mod. Methods Biochem.\u2013M. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/cbdd.13909","article-title":"Alpha-Amylase as Molecular Target for Treatment of Diabetes Mellitus: A Comprehensive Review","volume":"98","author":"Kaur","year":"2021","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Antony Samy, J.V.R., Kumar, N., Singaravel, S., Krishnamoorthy, R., Alshuniaber, M.A., Gatasheh, M.K., Venkatesan, A., Natesan, V., and Kim, S.J. (2023). Effect of Prunetin on Streptozotocin-Induced Diabetic Nephropathy in Rats\u2014A Biochemical and Molecular Approach. Biomol. Ther., 31.","DOI":"10.4062\/biomolther.2023.068"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/4\/2166\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:58:26Z","timestamp":1760104706000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/4\/2166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,10]]},"references-count":61,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25042166"],"URL":"https:\/\/doi.org\/10.3390\/ijms25042166","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,10]]}}}