{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T23:28:18Z","timestamp":1786663698513,"version":"build-2736575974"},"reference-count":80,"publisher":"Georg Thieme Verlag KG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"abstract":"<jats:p>Diabetes mellitus (DM) is a chronic metabolic disorder that continues to pose\n                        a major healthcare challenge worldwide. Despite the availability of several\n                        therapeutic options, achieving sustained glycaemic control and preventing\n                        long-term complications remain difficult in many patients. Walnut\n                            (Juglans regia L.) has gained attention as a potential\n                        complementary approach because of its diverse bioactive constituents and\n                        reported metabolic benefits. This review discusses the mechanistic,\n                        preclinical, and clinical evidence supporting the role of J. regia in\n                        diabetes management. The available studies indicate that walnut contains\n                        several phytochemicals, including juglone, flavonoids, polyphenols, and\n                        polyunsaturated fatty acids, which may contribute to antioxidant,\n                        anti-inflammatory, and insulin-sensitizing activities. Experimental findings\n                        suggest that these constituents help improve glucose homeostasis, protect\n                        pancreatic \u03b2-cells, and regulate insulin-signalling pathways. Preclinical\n                        studies consistently demonstrate beneficial effects on glycaemic parameters\n                        and pancreatic function, while clinical investigations report modest\n                        improvements in fasting blood glucose, HbA1c, and lipid profiles with good\n                        tolerability. However, differences in extract preparation, dosage, study\n                        design, and duration limit direct comparison among studies and highlight the\n                        need for further standardization. Future research should focus on\n                        well-designed clinical trials, optimized dosing strategies, and the\n                        evaluation of walnut preparations as adjuncts to conventional antidiabetic\n                        therapy. Overall, the current evidence supports J. regia as a\n                        promising complementary candidate for diabetes management and provides a\n                        basis for its further clinical development.<\/jats:p>","DOI":"10.1055\/a-2926-6431","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T23:01:23Z","timestamp":1786662083000},"source":"Crossref","is-referenced-by-count":0,"title":["Walnut (Juglans regia L.) as a Promising Antidiabetic Agent:\n                    Mechanistic, Preclinical, and Clinical Evidence"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0127-2123","authenticated-orcid":false,"given":"Deepshikha","family":"Patle","sequence":"additional","affiliation":[{"name":"Lovely Professional University, Punjab, India","place":["Phagwara"],"department":["Pharmaceutical Chemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Husam Najm A.","family":"Fazea","sequence":"additional","affiliation":[{"name":"Lovely Professional University, Punjab, India","place":["Phagwara"],"department":["Pharmaceutical Chemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1-10\ufeff2281","DOI":"10.4081\/hls.2024.12233","article-title":"The consumption of walnuts has an impact on decreasing fasting blood\n                    glucose levels in individuals with concurrent hyperglycemia and hyperlipidemia:\n                    A randomized control trial","volume":"12","author":"I Sukmawati","year":"2024","journal-title":"Healthc Low Resour Settings"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"102954","DOI":"10.1016\/j.fbio.2023.102954","article-title":"Activity, Structural Features and in Silico Digestion of Antidiabetic\n                    Peptides","volume":"55","author":"C Berraquero-Garc\u00eda","year":"2023","journal-title":"Food Biosc"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF diabetes atlas: Global, regional and country-level diabetes prevalence\n                    estimates for 2021 and projections for 2045","volume":"183","author":"H Sun","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"issue":"10","key":"ref4","doi-asserted-by":"crossref","first-page":"e1576","DOI":"10.1016\/S2214-109X(23)00348-0","article-title":"Diabetes risk and provision of diabetes prevention activities in 44 low-income\n                    and middle-income countries: A cross-sectional analysis of nationally\n                    representative, individual-level survey data","volume":"11","author":"N E Rahim","year":"2023","journal-title":"Lancet Global 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Forouhi","year":"2014","journal-title":"Medicine"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"100350","DOI":"10.1016\/j.bcdf.2023.100350","article-title":"Antidiabetic activity of polysaccharide from hypsizygus ulmarius in\n                    streptozotocin-nicotinamide induced diabetic rats","volume":"29","author":"S Govindan","year":"2023","journal-title":"Bioact Carbohydr Diet Fibre"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"103885","DOI":"10.1016\/j.fbio.2024.103885","article-title":"Comparative UHPLC-MS\/MS-based untargeted metabolomics analysis, antioxidant, and\n                    anti-diabetic activities of six walnut cultivars","volume":"59","author":"A Zeb","year":"2024","journal-title":"Food Biosci"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"134861","DOI":"10.1016\/j.molstruc.2022.134861","article-title":"Design, synthesis, and biological evaluation of coixol-based derivatives as\n                    potential antidiabetic agents","volume":"1277","author":"D Patle","year":"2023","journal-title":"J Mol Struct"},{"issue":"03","key":"ref11","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural products as sources of new drugs over the nearly four decades from\n                    01\/1981 to 09\/2019","volume":"83","author":"D J Newman","year":"2020","journal-title":"J Nat Prod"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"127","DOI":"10.21276\/apjhs.2022.9.4S1.22","article-title":"Identification of novel coixol-based derivatives as the potential anti-diabetic\n                    agents through molecular docking studies","volume":"9","author":"D Patle","year":"2022","journal-title":"Asian Pac J Health Sci"},{"issue":"02","key":"ref13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.31183\/imcp.2023.00079","article-title":"In vivo assessment of antidiabetic activity and safety of polyherbal teas from\n                    selected Cameroonian medicinal plants: Persea americana, Ageratum conyzoides and\n                    Mangifera indica","volume":"6","author":"D Zofou","year":"2023","journal-title":"Investig Med Chem Pharmacol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3389\/fphar.2013.00177","article-title":"The growing use of herbal medicines: Issues relating to adverse reactions and\n                    challenges in monitoring safety","volume":"4","author":"M Ekor","year":"2014","journal-title":"Front Pharmacol"},{"issue":"01","key":"ref15","first-page":"15","article-title":"Potential effects of curry (Murraya koenigii) and walnut leaves (Juglans regia)\n                    on diabetic rats induced by alloxan","volume":"33","author":"M Mahran","year":"2023","journal-title":"J Home Econ Menofia Univ"},{"key":"ref16","first-page":"2867","article-title":"A review on walnut: Its pharmacological properties and role in human\n                    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Mate\u0219","year":"2023","journal-title":"Antioxidants"},{"issue":"02","key":"ref20","doi-asserted-by":"publisher","first-page":"258","DOI":"10.3390\/nu15020258","article-title":"Adding walnuts to the usual diet can improve diet quality in the United States:\n                    Diet modeling study based on NHANES 2015\u20132018","volume":"15","author":"L A Spence","year":"2023","journal-title":"Nutrients"},{"issue":"12","key":"ref21","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.2337\/diacare.27.12.2777","article-title":"Including walnuts in a low-fat\/modified-fat diet improves HDL\n                    cholesterol-to-total cholesterol ratios in patients with type 2 diabetes","volume":"27","author":"L C Tapsell","year":"2004","journal-title":"Diabetes Care"},{"issue":"03","key":"ref22","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00125-022-05857-5","article-title":"Cardiovascular outcomes in type 1 and type 2 diabetes","volume":"66","author":"A Rosengren","year":"2023","journal-title":"Diabetologia"},{"issue":"01","key":"ref23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.36877\/pmmb.a0000325","article-title":"Bioactivity of walnut: Investigating\n                    the triterpenoid saponin extracts of juglans regia kernels for antioxidant,\n                    anti-diabetic, and antimicrobial properties","volume":"6","author":"Y Elouafy","year":"2023","journal-title":"Prog Microbes Mol\n                    Biol"},{"issue":"01","key":"ref24","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.fct.2009.10.043","article-title":"Human cancer cell antiproliferative and antioxidant activities of juglans regia\n                    L","volume":"48","author":"M Carvalho","year":"2010","journal-title":"Food Chem Toxicol"},{"issue":"03","key":"ref25","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1002\/jsfa.8542","article-title":"Kernel oil content and oil composition in walnut (Juglans regia L.) accessions\n                    from north-eastern Italy","volume":"98","author":"L Poggetti","year":"2018","journal-title":"J Sci Food Agric"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"100142","DOI":"10.1016\/j.obmed.2019.100142","article-title":"A review of phytochemistry and pharmacology profile of Juglans regia","volume":"16","author":"A Gupta","year":"2019","journal-title":"Obes Med"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1101\/2023.06.15.545164","article-title":"Exploring phytoconstituents of Juglans regia to treat cervical cancer\n                    using integrative","volume":"11","author":"R Dua","year":"2023","journal-title":"Bioinformatics"},{"key":"ref28","first-page":"1","article-title":"The phytochemical profiles for walnuts (J. Regia and J. Sigillata) from china\n                    with protected geographical indications","volume":"2061","author":"R Wang","year":"2020","journal-title":"Food Sci Technol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"27519","DOI":"10.1007\/s13399-022-03633-4","article-title":"Chemical constituents of green peel of Persian walnut (Juglans regia\n                    L.) fruit","volume":"14","author":"E ZamaniBahramabadi","year":"2022","journal-title":"Biomass Convers Biorefin"},{"issue":"11","key":"ref30","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.2522\/ptj.20080008","article-title":"Diabetes-related microvascular and macrovascular diseases in the physical\n                    therapy setting","volume":"88","author":"W T Cade","year":"2008","journal-title":"Phys Ther"},{"issue":"09","key":"ref31","first-page":"e45835","article-title":"Cardiovascular complications of diabetes: From microvascular to macrovascular\n                    pathways","volume":"15","author":"M Zakir","year":"2023","journal-title":"Cureus"},{"issue":"08","key":"ref32","doi-asserted-by":"publisher","first-page":"107613","DOI":"10.1016\/j.jdiacomp.2020.107613","article-title":"Molecular complexities underlying the vascular complications of diabetes\n                    mellitus\u2014A comprehensive review","volume":"34","author":"S Paul","year":"2020","journal-title":"J Diabetes Complications"},{"issue":"08","key":"ref33","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.3390\/cells11081312","article-title":"Advanced glycation end-products (AGEs): Formation, chemistry, classification,\n                    receptors, and diseases related to AGEs","volume":"11","author":"A Twarda-Clapa","year":"2022","journal-title":"Cells"},{"issue":"03","key":"ref34","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.cmet.2018.08.014","article-title":"The role of advanced glycation end products in aging and metabolic diseases:\n                    Bridging association and causality","volume":"28","author":"J Chaudhuri","year":"2018","journal-title":"Cell Metab"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fendo.2013.00068","article-title":"Diabetes alters activation and repression of pro- and anti-inflammatory\n                    signaling pathways in the vasculature","volume":"4","author":"E Di Marco","year":"2013","journal-title":"Front Endocrinol"},{"key":"ref36","first-page":"103","article-title":"Juglans regia in Europe: Distribution, habitat, usage and threats","volume":"8","author":"D D Rigo","year":"2016","journal-title":"Eur Atlas Forest Tree Species"},{"issue":"04","key":"ref37","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1007\/s43538-022-00119-9","article-title":"A comprehensive review on ethnobotanical, medicinal and nutritional potential of\n                    walnut (Juglans regia L.)","volume":"88","author":"M Sharma","year":"2022","journal-title":"Proce Indian Natl Sci Acad"},{"key":"ref38","first-page":"2278","article-title":"Juglans Regia\u2014a Review","volume":"5","author":"M S Wani","year":"2016","journal-title":"Int J Latest Res Sci Technol"},{"issue":"01","key":"ref39","doi-asserted-by":"publisher","first-page":"e34726","DOI":"10.5812\/ijem.34726.Research","article-title":"Chemical composition and the effect of walnut hydrosol on glycemic control of\n                    patients with type 1 diabetes","volume":"14","author":"H Moravej","year":"2016","journal-title":"Int J Endocrinol Metab"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1055\/s-0035-1546131","article-title":"Natural products for the treatment of type 2 diabetes mellitus","volume":"81","author":"J L Rios","year":"2015","journal-title":"Planta Med"},{"issue":"19","key":"ref41","doi-asserted-by":"publisher","first-page":"10323","DOI":"10.3390\/ijms251910323","article-title":"A comprehensive review of molecular mechanisms, pharmacokinetics, toxicology and\n                    plant sources of juglanin: Current landscape and future perspectives","volume":"25","author":"M Rutkowska","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"469","DOI":"10.3390\/toxins10110469","article-title":"Natural products to fight cancer: A focus on juglans regia","volume":"10","author":"E Catanzaro","year":"2018","journal-title":"Toxins"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"12","DOI":"10.5281\/zenodo.10257429","article-title":"Current aspects of the medical application of walnut (Juglans regia l.) and\n                    black walnut (Juglans nigra l.) (review)","volume":"6","author":"I Mozhaiev","year":"2023","journal-title":"Ann Mechnikov\u2019s Inst"},{"issue":"05","key":"ref44","doi-asserted-by":"crossref","first-page":"998","DOI":"10.5530\/pj.2024.16.161","article-title":"Juglans regia L.: Source of bioactive compounds with potential anticancer\n                    activity","volume":"16","author":"C Y Requejo-Rodr\u00edguez","year":"2024","journal-title":"Pharmacogn J"},{"issue":"01","key":"ref45","first-page":"26","article-title":"A review of the effect of walnuts (Juglans regia) supplementation on type 2\n                    diabetes mellitus","volume":"7","author":"C C Ofor","year":"2024","journal-title":"Asian J Res Rep Endocrinol"},{"issue":"11","key":"ref46","doi-asserted-by":"crossref","first-page":"988","DOI":"10.3390\/f10110988","article-title":"Polyphenolic profile and antioxidant activity of Juglans regia L. leaves and\n                    husk extracts","volume":"10","author":"A Masek","year":"2019","journal-title":"Forests"},{"key":"ref47","first-page":"304","article-title":"Hepatic mechanisms of the walnut antidiabetic effect in mice","volume":"5","author":"H Kamyab","year":"2010","journal-title":"Cent Eur J Biol"},{"issue":"01","key":"ref48","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/2008-2231-22-19","article-title":"The hypoglycemic effect of juglans regia leaves aqueous extract in diabetic\n                    patients: A first human trial","volume":"22","author":"S Hosseini","year":"2014","journal-title":"Daru J Pharm Sci"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.3390\/nu11071699","article-title":"N-3 polyunsaturated fatty acids decrease long-term diabetic risk of offspring of\n                    gestational diabetes rats by postponing shortening of hepatic telomeres and\n                    modulating liver metabolism","volume":"11","author":"J Gao","year":"2019","journal-title":"Nutrients"},{"issue":"04","key":"ref50","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1007\/s00394-017-1552-6","article-title":"Antidiabetic plant-derived nutraceuticals: A critical review","volume":"57","author":"J Naveen","year":"2018","journal-title":"Eur J Nutr"},{"key":"ref51","first-page":"1","article-title":"Beneficial effects of walnut (Juglans Regia L.) oil-derived polyunsaturated\n                    fatty acid prevents a prooxidant status and hyperlipidemia in pregnant rats with\n                    diabetes","volume":"17","author":"B Sun","year":"2020","journal-title":"Nutr Metab"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"112659","DOI":"10.1016\/j.jep.2020.112659","article-title":"Identifying potential active components of walnut leaf that action diabetes\n                    mellitus through integration of UHPLC-Q-Orbitrap HRMS and network pharmacology\n                    analysis","volume":"253","author":"R Liu","year":"2020","journal-title":"J Ethnopharmacol"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic\n                    reviews","volume":"372","author":"M J Page","year":"2021","journal-title":"BMJ"},{"issue":"03","key":"ref54","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.aimed.2017.10.001","article-title":"Anti-hyperglycemic effect of aqueous extract of juglans regia L. 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Fruit, stem and leaf.\u201d","volume":"50","author":"X Wang","year":"2015","journal-title":"Int J Food Sci Technol"},{"issue":"04","key":"ref56","first-page":"685","article-title":"Anti-diabetic effects of an alcoholic extract of Juglans regia in an animal\n                    model","volume":"41","author":"J Mohammadi","year":"2011","journal-title":"Turk J Med Sci"},{"issue":"24","key":"ref57","first-page":"2655","article-title":"Anti-diabetic effects of walnut oil on alloxan-induced diabetic rats","volume":"5","author":"P Rahimi","year":"2011","journal-title":"Afr J Pharm Pharmacol"},{"issue":"04","key":"ref58","doi-asserted-by":"crossref","first-page":"102018","DOI":"10.1016\/j.jksus.2022.102018","article-title":"A vegetable oil blend administration mitigates the hyperglycemia-induced redox\n                    imbalance, renal histopathology, and function in diabetic nephropathy","volume":"34","author":"S Anwar","year":"2022","journal-title":"J King Saud Univ 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Physiol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"8982676","DOI":"10.1155\/2020\/8982676","article-title":"Prevention of diabetic complications by walnut leaf extract via\n                    changing aldose reductase activity: An experiment in diabetic rat\n                    tissue","volume":"2020","author":"Z Abbasi","year":"2020","journal-title":"J Diabetes Res"},{"issue":"06","key":"ref66","doi-asserted-by":"crossref","first-page":"5538","DOI":"10.1039\/D0FO00670J","article-title":"Glycolipid Metabolism and liver transcriptomic analysis of the therapeutic\n                    effects of pressed degreased walnut meal extracts on type 2 diabetes mellitus\n                    rats","volume":"11","author":"Y Li","year":"2020","journal-title":"Food Funct"},{"issue":"01","key":"ref67","doi-asserted-by":"crossref","first-page":"e14348","DOI":"10.14814\/phy2.14348","article-title":"Cyclohexane extract of walnut leaves improves indices of oxidative stress, total\n        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Res"},{"issue":"02","key":"ref70","first-page":"135","article-title":"Tetracarpidium conophorum (African walnut) seeds protects against\n                    diabetes-induced liver damage in rats treated with streptozotocin","volume":"27","author":"B S Ajilore","year":"2020","journal-title":"Rom J Diabetes Nutr Metab Dis"},{"key":"ref71","first-page":"124974","article-title":"Antihyperglycaemic effect of tetracarpidium conophorum nuts in alloxan induced\n                    diabetic female albino rats","volume":"2014","author":"D O Onwuli","year":"2014","journal-title":"Int Sch Res Notices"},{"issue":"01","key":"ref72","first-page":"10","article-title":"Effect of aqueous extract of walnut septum on blood glucose and pancreatic\n                    structure in streptozotocin-induced diabetic mouse","volume":"11","author":"F Dehghani","year":"2012","journal-title":"Iran J Pharmacol 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