{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T20:30:14Z","timestamp":1787689814961,"version":"build-2784847793"},"reference-count":29,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Federal University of Technology, Akure, Nigeria"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Studies utilizing cell-based systems to investigate plant-based diets for diabetes management are gaining attention due to the adverse effects associated with commercially available drugs. However, the molecular mechanisms underlying the anti-diabetic effects of specific plant-derived products remain inadequately explored. The major aim of our study was to elucidate the molecular mechanisms by which bioactive compounds in the fruit of Solanum spp. influence key proteins associated with type 2 diabetes. The expressions of genes such as glucose transporter protein 4 (GLUT4), myocyte enhancer factor-2 (MEF-2A), and nuclear respiratory factor-1 (NRF-1) were investigated in a palmitate-induced C2C12 cell model of type 2 diabetes mellitus. The structures of these proteins were retrieved from the protein database, while bioactive compounds previously identified in Solanum spp. were obtained from PubChem site. Drug-likeness properties of these compounds (ligands) were assessed. The docked protein-ligand complexes were further analyzed using the Protein-Ligand Profiler web server. Our results showed that the studied compounds from Solanum spp. profoundly upregulated GLUT4 expression (9\u201319-fold increase) in the C2C12 cell line, thus surpassing the effects of the standard anti-diabetic drug metformin. Additionally, activities of antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase were elevated. Molecular docking showed that rutin, an abundant flavonoid from Solanum spp., had the highest binding affinity for the active sites of the target proteins. These findings provide new mechanistic insight into the anti-diabetic effects of Solanum spp., primarily due to its high rutin content, which plays a major role in the plant\u2019s glucose-regulating and antioxidant actions. Our findings underscore the potential use of Solanum spp. as an affordable functional food for managing type 2 diabetes, especially in developing countries with limited resources for purchasing drugs. Although promising, our findings should be further validated by clinical studies.<\/jats:p>","DOI":"10.3390\/ijms26167762","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T14:32:36Z","timestamp":1754922756000},"page":"7762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Eggplant (Solanum spp.) Fruits Dietary Polyphenols Upregulate the Expression of Glucose Transporter Protein in Palmitate-Induced Diabetic Cell Line C2C12"],"prefix":"10.3390","volume":"26","author":[{"given":"Esther E.","family":"Nwanna","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Federal University of Technology, P.M.B. 704, Akure 340252, Nigeria"},{"name":"Veterinary Medicine Teaching and Research Center, School of Veterinary Medicine, University of California, Davis, Tulare, CA 93274, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8800-955X","authenticated-orcid":false,"given":"Emmanuel","family":"Mukwevho","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Northwest University, Private Bag X2046, Mmabatho 2735, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1746-8385","authenticated-orcid":false,"given":"Emmanuel","family":"Okello","sequence":"additional","affiliation":[{"name":"Veterinary Medicine Teaching and Research Center, School of Veterinary Medicine, University of California, Davis, Tulare, CA 93274, USA"},{"name":"Department of Population Health & Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-6881","authenticated-orcid":false,"given":"Ademola O.","family":"Ayeleso","sequence":"additional","affiliation":[{"name":"Biochemistry Programme, Bowen University, P.M.B. 284, Iwo 220103, Nigeria"},{"name":"Department of Life and Consumer Sciences, University of South Africa, Florida Park, Roodeport 1709, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel O.","family":"Ibukun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Federal University of Technology, P.M.B. 704, Akure 340252, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganiyu","family":"Oboh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Federal University of Technology, P.M.B. 704, Akure 340252, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nwanna, E.E., Ibukun, E.O., and Oboh, G. (2019). Eggplant (Solanum spp.) supplemented fruits diet modulated the activities of ectonucleoside triphosphate diphosphohydrolase (ENTPdase), monoamine oxidase (MAO), and cholinesterases (AChE\/BChE) in the brain of diabetic Wistar male rats. J. Food Biochem., 43.","DOI":"10.1111\/jfbc.12910"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rana, J.N., and Mumtaz, S. (2025). Prunin: An Emerging Anticancer Flavonoid. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062678"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"186","DOI":"10.3390\/diabetology4020019","article-title":"Diabetes Mellitus Management: An Extensive Review of 37 Medicinal Plants","volume":"4","author":"Zanzabil","year":"2023","journal-title":"Diabetology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"E582","DOI":"10.1152\/ajpendo.00312.2007","article-title":"Caffeine induces hyperacetylation of histones at the MEF2 site on the Glut4 promoter and increases MEF2A binding to the site via a CaMK-dependent mechanism","volume":"294","author":"Mukwevho","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e074068","DOI":"10.1136\/bmj-2022-074068","article-title":"Benefits and harms of drug treatment for type 2 diabetes: Systematic review and network meta-analysis of randomised controlled trials","volume":"381","author":"Shi","year":"2023","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sharma, M., and Kaushik, P. (2021). Biochemical Composition of Eggplant Fruits: A Review. Appl. Sci., 11.","DOI":"10.3390\/app11157078"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kole, C. (2023). Eggplant (Solanum melongena L.) Nutritional and Health Promoting Phytochemicals. Compendium of Crop Genome Designing for Nutraceuticals, Springer.","DOI":"10.1007\/978-981-19-4169-6"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.1038\/s41467-022-30235-5","article-title":"Cryo-EM structure of human glucose transporter GLUT4","volume":"13","author":"Yuan","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5378","DOI":"10.1093\/nar\/gks189","article-title":"Inhibition of the function of class IIa HDACs by blocking their interaction with MEF2","volume":"40","author":"Jayathilaka","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/cmdc.201300525","article-title":"Binding Mode and Structure\u2013Activity Relationships around Direct Inhibitors of the Nrf2\u2013Keap1 Complex","volume":"9","author":"Jnoff","year":"2014","journal-title":"ChemMedChem"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nwanna, E., Ojo, R., Shafiq, N., Ali, A., Okello, E., and Oboh, G. (2024). An in Silico In Vitro and In Vivo Study on the Influence of an Eggplant Fruit (Solanum anguivi Lam) Diet on Metabolic Dysfunction in the Sucrose-Induced Diabetic-like Fruit Fly (Drosophila melanogaster). Foods, 13.","DOI":"10.3390\/foods13040559"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ayeleso, T.B., Matumba, M.G., and Mukwevho, E. (2017). Oleanolic Acid and Its Derivatives: Biological Activities and Therapeutic Potential in Chronic Diseases. Molecules, 22.","DOI":"10.3390\/molecules22111915"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.phymed.2013.03.018","article-title":"Amelioration of palmitate-induced insulin resistance in C2C12 muscle cells by Rooibos (Aspalathus lineraris)","volume":"20","author":"Mazibuko","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1042\/BJ20060244","article-title":"Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells","volume":"399","author":"Dimopoulos","year":"2006","journal-title":"Biochem. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1210\/er.2009-0027","article-title":"The role of mitochondria in the pathogenesis of type 2 diabetes","volume":"31","author":"Patti","year":"2010","journal-title":"Endocr. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jsps.2016.04.025","article-title":"The Pharmacological Potential of Rutin","volume":"25","author":"Ganeshpurkar","year":"2017","journal-title":"Saudi Pharm. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"615","DOI":"10.2337\/diab.45.5.615","article-title":"Mechanisms Behind Insulin Resistance in Rat Skeletal Muscle After Oophorectomy and Additional Testosterone Treatment","volume":"45","author":"Rincon","year":"1996","journal-title":"Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng1180","article-title":"PGC-1\u03b1-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes","volume":"34","author":"Mootha","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jep.2012.07.004","article-title":"Pomegranate peel and fruit extracts: A review of potential anti-inflammatory and anti-infective effects","volume":"143","author":"Ismail","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_20","first-page":"43","article-title":"In vitro evaluation of antioxidant, antiproliferative potentials of bioactive extract-cum-rutin compound Isolated from Memecylon edule leaves and its molecular docking study","volume":"6","author":"Srinivasan","year":"2016","journal-title":"J. Biol. Act. Prod. Nat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/biof.5520260405","article-title":"Anti-adipogenic activity of rutin in 3T3-L1 cells and mice fed with high-fat diet","volume":"26","author":"Choi","year":"2006","journal-title":"BioFactors"},{"key":"ref_22","first-page":"98","article-title":"Phytochemical screening and extraction: A review","volume":"1","author":"Tiwari","year":"2011","journal-title":"Int. Pharm. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"251","DOI":"10.5455\/OVJ.2021.v11.i2.9","article-title":"The MTT assay application to measure the viability of spermatozoa: A variety of the assay protocols","volume":"11","author":"Buranaamnuay","year":"2021","journal-title":"Open Vet. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0891-5849(98)00315-3","article-title":"Antioxidant activity applying an improved ABTS radical cation decolorization assay","volume":"26","author":"Re","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1006\/abio.1996.0292","article-title":"The Ferric Reducing Ability of Plasma (FRAP) as a Measure of \u201cAntioxidant Power\u201d: The FRAP Assay","volume":"239","author":"Benzie","year":"1996","journal-title":"Anal. Biochem."},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1038\/nprot.2006.378","article-title":"Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method","volume":"1","author":"Rahman","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hadwan, M.H., Hussein, M.J., Mohammed, R.M., Hadwan, A.M., Al-Kawaz, H.S., Al-Obaidy, S.S.M., and Al Talebi, Z.A. (2024). An improved method for measuring catalase activity in biological samples. Biol. Methods Protoc., 9.","DOI":"10.1093\/biomethods\/bpae015"},{"key":"ref_29","unstructured":"Zar, J.H. (1998). Biostatistical Analysis, Prentice Hall. [4th ed.]."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/7762\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:25:02Z","timestamp":1760034302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/7762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":29,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26167762"],"URL":"https:\/\/doi.org\/10.3390\/ijms26167762","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,11]]}}}