{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T04:45:25Z","timestamp":1782621925110,"version":"3.54.5"},"reference-count":48,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Ficus carica L. is traditionally used for diabetes management. This study evaluated the antihyperglycemic activity, safety, possible mechanisms, and phytochemical composition of its aqueous leaf extract (EAcFc). EAcFC activity was evaluated in streptozotocin\u2013nicotinamide-induced type 2 diabetic (ST2D) mice under acute and subchronic conditions. EAcFc showed low acute toxicity (LD50 &gt; 3000 mg\/kg). Acute and subchronic oral administration of EAcFc (300 mg\/kg) significantly reduced blood glucose levels in ST2D mice. Although sustained HbA1c reduction was not observed, EAcFc improved lipid profiles, notably reducing triglyceride concentrations in ST2D males (from 156 \u00b1 19.4 to 89.7 \u00b1 3.3 mg\/dL at week 4) and females (from 138 \u00b1 2.0 to 77 \u00b1 16.0 mg\/dL at week 4). In oral sucrose and lactose tolerance tests (3 g\/kg load), EAcFc (300 mg\/kg) significantly attenuated postprandial hyperglycemia at 30, 60, and 120 min, an effect comparable to acarbose (50 mg\/kg). No significant activity was observed during the oral glucose tolerance test (1.5 mg\/kg load), suggesting the effect is not mediated by SGLT-1 inhibition. Preparative TLC and NMR analysis identified narcissin, nicotiflorin, and \u03b2-sitosterol. Thus, EAcFc possesses antihyperglycemic and lipid-modulating properties partially associated with \u03b1-glucosidase inhibition and bioactive flavonoids and phytosterol.<\/jats:p>","DOI":"10.3390\/molecules31132207","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:11:49Z","timestamp":1782234709000},"page":"2207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterizing the Antihyperglycemic Activity and Underlying Mechanisms of the Aqueous Extract of the Leaves from Ficus carica L."],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1851-5988","authenticated-orcid":false,"given":"Fernando","family":"Calzada","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Farmacolog\u00eda, UMAE Hospital de Especialidades, 2\u00b0 Piso CORSE, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Mexico City 06725, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2673-4366","authenticated-orcid":false,"given":"Jesica","family":"Ram\u00edrez-Santos","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Farmacolog\u00eda, UMAE Hospital de Especialidades, 2\u00b0 Piso CORSE, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Mexico City 06725, Mexico"},{"name":"Instituto Polit\u00e9cnico Nacional, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n S\/N, Col. Casco de Santo Tom\u00e1s, Miguel Hidalgo, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannia","family":"P\u00e9rez-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Farmacolog\u00eda, UMAE Hospital de Especialidades, 2\u00b0 Piso CORSE, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Mexico City 06725, Mexico"},{"name":"Facultad de Medicina, Universidad Veracruzana, Agust\u00edn de Iturbide S\/N, Zona Centro, Veracruz 91700, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7401-303X","authenticated-orcid":false,"given":"Miguel","family":"Valdes","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Farmacolog\u00eda, UMAE Hospital de Especialidades, 2\u00b0 Piso CORSE, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Col. Doctores, Mexico City 06725, Mexico"},{"name":"Instituto Polit\u00e9cnico Nacional, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n S\/N, Col. Casco de Santo Tom\u00e1s, Miguel Hidalgo, Mexico City 11340, Mexico"},{"name":"Laboratorio de Inmunolog\u00eda, Departamento de Sistemas Biol\u00f3gicos, Universidad Aut\u00f3noma Metropolitana Unidad Xochimilco, Calz. del Hueso 1100, Coapa, Villa Quietud, Coyoac\u00e1n, Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7111-7922","authenticated-orcid":false,"given":"Elizabeth","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Instituto Polit\u00e9cnico Nacional, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n S\/N, Col. Casco de Santo Tom\u00e1s, Miguel Hidalgo, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0546-5969","authenticated-orcid":false,"given":"Claudia","family":"Vel\u00e1zquez","sequence":"additional","affiliation":[{"name":"\u00c1rea Acad\u00e9mica de Farmacia, Instituto de Ciencias de la Salud, Universidad Aut\u00f3noma del Estado de Hidalgo, Circuito ex Hacienda La Concepci\u00f3n S\/N, Carretera Pachuca-Atocpan, San Agustin Tlaxcala 42076, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2026, April 20). Available online: https:\/\/www.who.int\/es\/news-room\/fact-sheets\/detail\/diabetes."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.2337\/dc23-Sint","article-title":"Introduction and methodology: Standards of care in diabetes\u20142023","volume":"46","author":"ElSayed","year":"2022","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0140-6736(25)01079-7","article-title":"Worldwide trends in diabetes prevalence: The NCD-RisC study","volume":"406","author":"Boyko","year":"2025","journal-title":"Lancet"},{"key":"ref_4","unstructured":"International Diabetes Federation (2024). IDF Diabetes Atlas, International Diabetes Federation. [11th ed.]. Available online: https:\/\/diabetesatlas.org\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"725","DOI":"10.21149\/12842","article-title":"Prevalence of diabetes and glycemic control in Mexico: National results from 2018 and 2020","volume":"63","year":"2021","journal-title":"Salud P\u00fablica M\u00e9x."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15019","DOI":"10.1038\/nrdp.2015.19","article-title":"Type 2 diabetes mellitus","volume":"1","author":"DeFronzo","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K.B., and Mart\u00edn, C. (2020). Pathophysiology of type 2 diabetes mellitus. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176275"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1152\/physrev.00045.2011","article-title":"Mechanisms of diabetic complications","volume":"93","author":"Forbes","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.freeradbiomed.2022.03.019","article-title":"Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives","volume":"184","author":"Bhatti","year":"2022","journal-title":"Free Rad. Biol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"969080","DOI":"10.3389\/fendo.2022.969080","article-title":"The association between blood glucose levels and lipids or lipid ratios in type 2 diabetes patients: A cross-sectional study","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sharahili, A.Y., Mir, S.A., ALDosari, S., Manzar, M.D., Alshehri, B., Al Othaim, A., and Alotaibi, J.S. (2023). Correlation of HbA1c level with lipid profile in type 2 diabetes mellitus patients visiting a primary healthcare center in Jeddah City, Saudi Arabia: A retrospective cross-sectional study. Diseases, 11.","DOI":"10.3390\/diseases11040154"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"140","DOI":"10.2337\/dc14-2441","article-title":"Management of hyperglycemia in type 2 diabetes, 2015: A patient-centered approach: Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes","volume":"38","author":"Inzucchi","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1517\/14740338.2015.1006625","article-title":"Safety of dipeptidyl peptidase-4 inhibitors for treating type 2 diabetes","volume":"14","author":"Scheen","year":"2015","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.cmet.2014.08.005","article-title":"Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes","volume":"20","author":"Soccio","year":"2014","journal-title":"Cell Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1111\/dme.12144","article-title":"Pioglitazone and risk of bladder cancer: A meta-analysis of controlled studies","volume":"30","author":"Ferwana","year":"2013","journal-title":"Diabet. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"732","DOI":"10.3923\/ijp.2017.732.745","article-title":"Promising antidiabetic drugs, medicinal plants and herbs: An update","volume":"13","author":"Yatoo","year":"2017","journal-title":"Int. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3390\/ddc3010011","article-title":"Plant-derived natural products: A source for drug discovery and development","volume":"3","author":"Chaachouay","year":"2024","journal-title":"Drugs Drug Candidates"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jep.2017.12.045","article-title":"A role of Ficus species in the management of diabetes mellitus: A review","volume":"215","author":"Deepa","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6236","DOI":"10.62347\/MVBZ4789","article-title":"A review of Ficus L. genus (Moraceae): A source of bioactive compounds for health and disease. Part 1","volume":"16","year":"2024","journal-title":"Am. J. Transl. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rasool, I.F.U., Aziz, A., Khalid, W., Koraqi, H., Siddiqui, S.A., Al-Farga, A., and Ali, A. (2023). Industrial application and health prospective of fig (Ficus carica) by-products. Molecules, 28.","DOI":"10.3390\/molecules28030960"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"vvaf231","DOI":"10.1093\/ijfood\/vvaf231","article-title":"Fig (Ficus carica) as a source of bioactive compounds: Nutritional, medicinal, and food industry perspectives","volume":"60","author":"Khalid","year":"2025","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1016\/j.fct.2009.09.004","article-title":"Ficus carica L.: Metabolic and biological screening","volume":"47","author":"Oliveira","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"974256","DOI":"10.1155\/2013\/974256","article-title":"Ficus carica L. (Moraceae): Phytochemistry, traditional uses and biological activities","volume":"2013","author":"Mawa","year":"2013","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.3109\/13880209.2014.892515","article-title":"Traditional uses, phytochemistry and pharmacology of Ficus carica: A review","volume":"52","author":"Badgujar","year":"2014","journal-title":"Pharm. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.52711\/0974-360X.2021.00718","article-title":"Antihyperglycemic activity of Ficus carica leaves extracts on streptozotocin induced diabetic rats","volume":"14","author":"Roy","year":"2021","journal-title":"Res. J. Pharm. Technol."},{"key":"ref_26","unstructured":"OECD (2026, April 01). Guideline for Testing of Chemicals 423. Acute Oral Toxicity-Acute Toxic Class Method. Organizacion para la Cooperaci\u00f3n el Desarrollo Economicos, OECD\/OCDE. Available online: https:\/\/www.oecd.org\/content\/dam\/oecd\/en\/publications\/reports\/2002\/02\/test-no-423-acute-oral-toxicity-acute-toxic-class-method_g1gh294f\/9789264071001-en.pdf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16959","DOI":"10.3390\/molecules191016959","article-title":"Antioxidant, 5-lipoxygenase inhibitory and cytotoxic activities of compounds isolated from the Ferula lutea flowers","volume":"19","author":"Znati","year":"2014","journal-title":"Molecules"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1590\/S0102-695X2013005000061","article-title":"Flavonoids from leaves of Mauritia flexuosa","volume":"23","author":"Siqueira","year":"2013","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_29","first-page":"566","article-title":"Isolation, characterization, and docking studies of campesterol and \u03b2-sitosterol from Strychnos innocua (Delile) root bark","volume":"18","author":"Uttu","year":"2023","journal-title":"J. Taibah Univ. Med. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s40001-024-01739-1","article-title":"Advances in secondary prevention mechanisms of macrovascular complications in type 2 diabetes mellitus patients: A comprehensive review","volume":"29","author":"Guan","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_31","first-page":"113","article-title":"Antidiabetic potential of medicinal plants","volume":"67","author":"Malviya","year":"2010","journal-title":"Acta Pol. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"111393","DOI":"10.1016\/j.biopha.2021.111393","article-title":"A comprehensive review on phytochemistry, bioactivities, toxicity studies, and clinical studies on Ficus carica Linn. leaves","volume":"137","author":"Li","year":"2021","journal-title":"Biomed. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yan, L.J. (2022). The nicotinamide\/streptozotocin rodent model of type 2 diabetes: Renal pathophysiology and redox imbalance features. Biomolecules, 12.","DOI":"10.3390\/biom12091225"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez-Santos, J., Calzada, F., Mart\u00ednez-Rodr\u00edguez, J., Valdes, M., Barbosa, E., and Vel\u00e1zquez, C. (2025). Aqueous extracts and flavonoids obtained from Annona cherimola Miller as antidiabetic treatments alone and in combination with antidiabetic drugs: In vivo and in silico studies. Pharmaceuticals, 18.","DOI":"10.3390\/ph18111754"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"110237","DOI":"10.1016\/j.cbi.2022.110237","article-title":"Phytochemistry, biological activities, industrial and traditional uses of fig (Ficus carica): A review","volume":"368","author":"Hajam","year":"2022","journal-title":"Chem. Biol. Interact."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1080\/13880209.2017.1279671","article-title":"Protective effects of Ficus carica leaves on glucose and lipids levels, carbohydrate metabolism enzymes and \u03b2-cells in type 2 diabetic rats","volume":"55","author":"Christudas","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"979","DOI":"10.2147\/DMSO.S405150","article-title":"Chemical constituents and antidiabetic activity of dichloromethane extract from Ficus carica leaves","volume":"5","author":"Lin","year":"2023","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"97","DOI":"10.5114\/pedm.2025.153732","article-title":"Impact of fig leaf extract (Ficus carica L.) on GLUT-2 expression in pancreatic \u03b2 cells and hepatic cells of Wistar rats induced by streptozotocin-nicotinamide","volume":"31","author":"Ariyandy","year":"2025","journal-title":"Pediatr. Endocrinol. Diabetes Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/ptr.4994","article-title":"Ficus carica leaf extract modulates the lipid profile of rats fed with a high-fat diet through an increase of HDL-C","volume":"28","author":"Joerin","year":"2014","journal-title":"Phytother. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.2147\/VHRM.S3119","article-title":"Alpha-glucosidase inhibitors in the early treatment of type 2 diabetes","volume":"4","year":"2008","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.2337\/dc12-2391","article-title":"Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: Results of a randomized, placebo-controlled study","volume":"36","author":"Polidori","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Petruccelli, R., Giordano, C., Begh\u00e8, D., Arcidiaco, L., Bonetti, A., Ieri, F., and Ganino, T. (2025). Description of Ficus carica L. Italian Cultivars II: Genetic and Chemical Analysis. Plants, 14.","DOI":"10.3390\/plants14081238"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1080\/10408398.2011.561379","article-title":"Advance in dietary polyphenols as \u03b1-glucosidases inhibitors: A review on structure-activity relationship aspect","volume":"53","author":"Xiao","year":"2013","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_44","first-page":"1934578X1100600211","article-title":"\u03b1-Glucosidase inhibitory activity of kaempferol-3-O-rutinoside","volume":"6","author":"Habtemariam","year":"2011","journal-title":"Nat. Prod. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Prasad, M., Jayaraman, S., Eladl, M.A., El-Sherbiny, M., Abdelrahman, M.A.E., Veeraraghavan, V.P., and Rajagopal, P. (2022). A comprehensive review on therapeutic perspectives of phytosterols in insulin resistance: A mechanistic approach. Molecules, 27.","DOI":"10.3390\/molecules27051595"},{"key":"ref_46","unstructured":"Norma Oficial Mexicana (2026, April 05). NOM-062-ZOO-1999: Especificaciones T\u00e9cnicas Para la Producci\u00f3n, Cuidado y Uso de los Animales de Laboratorio. Available online: https:\/\/www.fmvz.unam.mx\/fmvz\/principal\/archivos\/062ZOO.PDF."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Sol\u00eds, J., Calzada, F., Barbosa, E., and Vald\u00e9s, M. (2021). Antihyperglycemic and antilipidemic properties of a tea infusion of the leaves from Annona cherimola miller on streptozotocin-induced type 2 diabetic mice. Molecules, 26.","DOI":"10.3390\/molecules26092408"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.jfda.2016.03.009","article-title":"Myrciaria cauliflora extract improves diabetic nephropathy via suppression of oxidative stress and inflammation in streptozotocin-nicotinamide mice","volume":"24","author":"Hsu","year":"2016","journal-title":"J. Food Drug Anal."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/13\/2207\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T04:10:19Z","timestamp":1782619819000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/13\/2207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":48,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["molecules31132207"],"URL":"https:\/\/doi.org\/10.3390\/molecules31132207","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]}}}