{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:53:26Z","timestamp":1791971606259,"version":"4.3.4"},"reference-count":55,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007846","name":"Yunnan Provincial Department of Education","doi-asserted-by":"publisher","award":["(C615300504054)"],"award-info":[{"award-number":["(C615300504054)"]}],"id":[{"id":"10.13039\/501100007846","id-type":"DOI","asserted-by":"publisher"}]},{"award":["(C615300504054)"],"award-info":[{"award-number":["(C615300504054)"]}],"id":[{"id":"https:\/\/ror.org\/02yrxdp92","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Diabetes mellitus (DM), a chronic metabolic disease that leads to damage to multiple organ systems, needs to be investigated in natural ways. The present experiment was performed to determine the anti-hyperglycaemic, nephroprotective and hepatoprotective potential of the methanolic extract of Wrightia tinctoria (W. tinctoria) seeds, and Enterococcus ratti (E. ratti), in alloxan-induced hyperglycaemic mice (150 mg\/kg body weight). W. tinctoria and E. ratti were screened out from different locally medicinally important plants and bacterial strains by different in vitro tests. W. tinctoria seeds showed \u03b1-amylase inhibition through the starch\u2013iodine test (88.64% at 100 mg\/mL), inhibition of glycosylation of haemoglobin (88.34% at 3.56 mg\/mL), and an inhibitory effect on glucose uptake by yeast cells (91.62% at 500 \u00b5g\/mL). Among various bacterial strains used for in vitro screening, E. ratti exhibited the most effective glucose adsorption capacity (26.2% at colony-forming unit (CFU) 1011). High-performance liquid chromatography (HPLC) and Fourier-transformed infrared (FT-IR) spectroscopy analyses provided preliminary information on the phytochemical composition of the extract. In vivo administration of W. tinctoria (200, 400 mg\/kg body weight), E. ratti (60 \u00b5L at a CFU 1011) alone and their combination produced significant dose-dependent improvements in treatment groups, with the combination demonstrating enhanced efficacy compared to individual treatments. Future research should focus on detailed mechanisms underlying these protective effects using transcriptomic and proteomic approaches and developing standardized formulation strategies for translation into clinical applications.<\/jats:p>","DOI":"10.3390\/ijms27198792","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:36:31Z","timestamp":1790786191000},"page":"8792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-Hyperglycaemic, Hepatoprotective, and Nephroprotective Effects of Wrightia tinctoria Seeds and Enterococcus ratti in Alloxan-Induced Diabetic Mice"],"prefix":"10.3390","volume":"27","author":[{"given":"Mohsin","family":"Munawar","sequence":"first","affiliation":[{"name":"State Key Laboratory of Vegetation Structure, Functions and Construction, and Yunnan Key Laboratory of Soil Erosion Prevention and Green Development, Yunnan University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Turab","family":"Raza","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Vegetation Structure, Functions and Construction, and Yunnan Key Laboratory of Soil Erosion Prevention and Green Development, Yunnan University, Kunming 650500, China"},{"name":"Yunnan Key Laboratory of Meteorological Disasters and Climate Resources in the Greater Mekong Sub Region, School of Earth Sciences, Yunnan University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zitouni, K., Steyn, M., Lewis, J., Kelly, F.J., Cook, P., and Earle, K.A. (2025). Variation in Arterial Stiffness and Markers of Oxidative Stress in Patients with Type 2 Diabetes Mellitus from Different Ethnic Groups. Antioxidants, 14.","DOI":"10.3390\/antiox14070858"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.pcd.2023.08.003","article-title":"Diabetes mellitus-related musculoskeletal disorders: Unveiling the cluster of diseases","volume":"17","author":"Csonka","year":"2023","journal-title":"Prim. Care Diabetes"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pe\u00f1a-Jorquera, H., Cid-Jofr\u00e9, V., Landaeta-D\u00edaz, L., Petermann-Rocha, F., Martorell, M., Zbinden-Foncea, H., and Cristi-Montero, C. (2023). Plant-based nutrition: Exploring health benefits for atherosclerosis, chronic diseases, and metabolic syndrome\u2014A comprehensive review. Nutrients, 15.","DOI":"10.3390\/nu15143244"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Scarpa, E.S., Antonelli, A., Balercia, G., Sabatelli, S., Maggi, F., Caprioli, G., and Micucci, M. (2024). Antioxidant, anti-inflammatory, anti-diabetic, and pro-osteogenic activities of polyphenols for the treatment of two different chronic diseases: Type 2 diabetes mellitus and osteoporosis. Biomolecules, 14.","DOI":"10.3390\/biom14070836"},{"key":"ref_5","first-page":"45","article-title":"Type 2 diabetes mellitus, oxidative stress and inflammation: Examining the links","volume":"11","author":"Oguntibeju","year":"2019","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2147\/DMSO.S495364","article-title":"AI-Driven Management of Type 2 Diabetes in China: Opportunities and Challenges","volume":"2025","author":"He","year":"2025","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100056","DOI":"10.1016\/j.fhfh.2022.100056","article-title":"Insights on \u03b2-glucan as a prebiotic coadjuvant in the treatment of diabetes mellitus: A review","volume":"2","author":"Sivieri","year":"2022","journal-title":"Food Hydrocoll. Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e34021","DOI":"10.1097\/MD.0000000000034021","article-title":"Prevalence of type 2 diabetes mellitus and related factors among the general adult population in Saudi Arabia between 2016\u20132022: A systematic review and meta-analysis of the cross-sectional studies","volume":"102","author":"Alwadeai","year":"2023","journal-title":"Medicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"210","DOI":"10.37022\/wjcmpr.v5i5.294","article-title":"Profiling of Clinical Dynamics of Type 2 Diabetes Mellitus in Patients: A Perspective Review","volume":"2","author":"Ikwuka","year":"2023","journal-title":"World J. Curr. Med. Pharm. Res."},{"key":"ref_10","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 estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11744","DOI":"10.1038\/s41598-023-39037-1","article-title":"The prevalence of peripheral neuropathy among the patients with diabetes in Pakistan: A systematic review and meta-analysis","volume":"13","author":"Akhtar","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2147\/CEOR.S247498","article-title":"Healthcare costs of diabetes and microvascular and macrovascular disease in individuals with incident type 2 diabetes mellitus: A ten-year longitudinal study","volume":"2020","author":"Visaria","year":"2020","journal-title":"Clin. Outcomes Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1038\/s41591-024-03264-4","article-title":"Finerenone in Heart Failure and Chronic Kidney Disease with Type 2 Diabetes: The FINE-HEART pooled analysis of cardiovascular, kidney, and mortality outcomes","volume":"30","author":"Vaduganathan","year":"2024","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Black, H.S. (2022). A synopsis of the associations of oxidative stress, ROS, and antioxidants with diabetes mellitus. Antioxidants, 11.","DOI":"10.3390\/antiox11102003"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"32","DOI":"10.4068\/cmj.2025.61.1.32","article-title":"Reactive Oxygen Species: Role in Pathophysiology, and Mechanism of Endogenous and Dietary Antioxidants during Oxidative Stress","volume":"61","author":"Sikder","year":"2025","journal-title":"Chonnam Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100186","DOI":"10.1016\/j.obmed.2020.100186","article-title":"Metformin: A review of its therapeutic efficacy and adverse effects","volume":"17","author":"Shurrab","year":"2020","journal-title":"Obes. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"437","DOI":"10.2174\/18756417MTExfMTQ1z","article-title":"Herbal medicines for diabetes management and its secondary complications","volume":"17","author":"Kumar","year":"2021","journal-title":"Curr. Diabetes Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Weinberg Sibony, R., Segev, O., Dor, S., and Raz, I. (2023). Drug Therapies for diabetes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417147"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ilan, Y. (2022). Next-generation personalized medicine: Implementation of variability patterns for overcoming drug resistance in chronic diseases. J. Pers. Med., 12.","DOI":"10.3390\/jpm12081303"},{"key":"ref_20","first-page":"1","article-title":"Medicinal and pharmacological action of various herbs on Diabetes mellitus: A review","volume":"13","author":"Sable","year":"2023","journal-title":"J. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100436","DOI":"10.1016\/j.hermed.2021.100436","article-title":"A review on medicinal plants evaluated for anti-diabetic potential in clinical trials: Present status and future perspective","volume":"28","author":"Naveen","year":"2021","journal-title":"J. Herb. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103614","DOI":"10.1016\/j.jff.2019.103614","article-title":"Evaluation of the hypoglycemic effect of probiotics via directly consuming glucose in intestines of STZ-induced diabetic mice and glucose water-induced diabetic mice","volume":"64","author":"Wang","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s11274-024-04226-1","article-title":"Exploring the antidiabetic activity of potential probiotic bacteria isolated from traditional fermented beverage","volume":"41","author":"Chutia","year":"2025","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104268","DOI":"10.1016\/j.meegid.2020.104268","article-title":"From role of gut microbiota to microbial-based therapies in type 2-diabetes","volume":"81","author":"Leylabadlo","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s00125-020-05295-1","article-title":"The effect of probiotics, prebiotics or synbiotics on metabolic outcomes in individuals with diabetes: A systematic review and meta-analysis","volume":"64","author":"Bock","year":"2021","journal-title":"Diabetologia"},{"key":"ref_26","first-page":"273","article-title":"Assessment on biological activities of Adhatoda vesica: A review","volume":"10","author":"Ahsen","year":"2020","journal-title":"Int. J. Res. Pharm. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1080\/07391102.2020.1821782","article-title":"In silico improvement of the cyanobacterial lectin microvirin and mannose interaction","volume":"40","author":"Lima","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.21608\/ejchem.2024.328645.10642","article-title":"GC\u2013MS and Molecular Docking Analyses of Phytochemicals from Calendula officinalis L. Hexane Extract and Evaluation of its Antioxidant and Wound Healing Properties in Rats","volume":"67","author":"Salama","year":"2024","journal-title":"Egypt. J. Chem."},{"key":"ref_29","first-page":"460","article-title":"Pharmacological activities of Calendula officinalis","volume":"9","author":"Pandey","year":"2022","journal-title":"Int. J. Res. Anal. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"116861","DOI":"10.1016\/j.jep.2023.116861","article-title":"A comprehensive review on Saraca asoca (Fabaceae)-Historical perspective, traditional uses, biological activities, and conservation","volume":"317","author":"Urumarudappa","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","first-page":"1113","article-title":"A review on Saraca indica","volume":"13","author":"Gawshinde","year":"2024","journal-title":"World J. Pharm. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"58","DOI":"10.56499\/jppres20.894_9.1.58","article-title":"Anti-hyperglycemic and hypolipidemic effects of Saraca asoca (Roxb.) Wild. flowers in alloxan-treated diabetic rats","volume":"9","author":"Thilagam","year":"2021","journal-title":"J. Pharm. Pharmacogn. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Popstoyanova, D., Gerasimova, A., Gentscheva, G., Nikolova, S., Gavrilova, A., and Nikolova, K. (2024). Ziziphus jujuba: Applications in the Pharmacy and Food Industry. Plants, 13.","DOI":"10.3390\/plants13192724"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s13668-024-00581-5","article-title":"Ziziphus jujuba (Jujube) in Metabolic Syndrome: From Traditional Medicine to Scientific Validation","volume":"13","author":"Hosseinzadeh","year":"2024","journal-title":"Curr. Nutr. Rep."},{"key":"ref_35","first-page":"5577163","article-title":"Antiamnesic and Neuroprotective. Effects of an Aqueous Extract of Ziziphus jujuba Mill. (Rhamnaceae) on Scopolamine-Induced Cognitive Impairments in Rats. Evid.-Based Complement","volume":"15","author":"Djeuzong","year":"2021","journal-title":"Altern. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lee, D., Kang, K.B., Hwang, G.S., Choi, Y.K., Kim, T.K., and Kang, K.S. (2021). Antioxidant and anti-inflammatory effects of 3-dehydroxyceanothetric acid 2-methyl ester Isolated from Ziziphus jujuba Mill. against Cisplatin-induced kidney epithelial cell death. Biomolecules, 11.","DOI":"10.3390\/biom11111614"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ijfoodmicro.2011.08.014","article-title":"Enterococci as probiotics and their implications in food safety","volume":"151","author":"Franz","year":"2011","journal-title":"Int. J. Food Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.29261\/pakvetj\/2018.093","article-title":"Characterization of Bacteriocin like inhibitory substances from Enterococcus ratti MF183967","volume":"39","author":"Riaz","year":"2019","journal-title":"Pak. Vet. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"125184","DOI":"10.1016\/j.ijbiomac.2023.125184","article-title":"Diabetic wound healing potential of silk sericin protein based hydrogels enriched with plant extracts","volume":"242","author":"Zahoor","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9250097","DOI":"10.26599\/FSHW.2024.9250097","article-title":"Polygonatum sibiricum saponin-lactic acid bacteria combination attenuate hyperglycemia in T2DM mice by modulating amino acid metabolism","volume":"14","author":"Luo","year":"2025","journal-title":"Food Sci. Hum. Wellness"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1093\/ajcp\/aqae129.082","article-title":"Enhanced Antidiabetic Effects of Gymnema sylvestre and Probiotics in Alloxan-Induced Diabetic Rats","volume":"162","author":"Abdelmonem","year":"2024","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1016\/S0140-6736(18)31320-5","article-title":"Type 1 diabetes","volume":"391","author":"DiMeglio","year":"2018","journal-title":"Lancet"},{"key":"ref_43","first-page":"261","article-title":"Prevention of non-enzymatic glycosylation (glycation): Implication in the treatment of diabetic complication","volume":"10","author":"Younus","year":"2016","journal-title":"Int. J. Health Sci."},{"key":"ref_44","first-page":"12","article-title":"Evaluation of in vitro antidiabetic activity of selected plant extracts","volume":"2","author":"Nair","year":"2013","journal-title":"Int. J. Pharm. Sci. Invent."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.foodchem.2007.05.077","article-title":"\u03b1-Glucosidase and \u03b1-amylase inhibitory activities of Nepalese medicinal herb Pakhanbhed (Bergenia ciliata, Haw.)","volume":"106","author":"Bhandari","year":"2008","journal-title":"Food Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"756","DOI":"10.3109\/13880209.2013.869828","article-title":"Evaluation of six plant species used traditionally in the treatment and control of diabetes mellitus in South Africa using in vitro methods","volume":"52","author":"Boaduo","year":"2014","journal-title":"Pharm. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s00125-007-0886-7","article-title":"The mechanisms of alloxan-and streptozotocin-induced diabetes","volume":"51","author":"Lenzen","year":"2008","journal-title":"Diabetologia"},{"key":"ref_48","first-page":"550","article-title":"Hypoglycemic and hypolipidemic activity of Wrightia tinctoria L. in alloxan induced diabetes in albino wistar rats","volume":"3","author":"Raj","year":"2009","journal-title":"Pharmacologyonline"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.5530\/pj.2021.13.204","article-title":"Antidiabetic activity of extract and fractions of Castanopsis costata leaves on alloxan-induced diabetic mice","volume":"13","author":"Alkandahri","year":"2021","journal-title":"Pharmacogn. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e10232","DOI":"10.7717\/peerj.10232","article-title":"Silk derived formulations for accelerated wound healing in diabetic mice","volume":"9","author":"Tariq","year":"2021","journal-title":"PeerJ"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/jpbs.JPBS_175_19","article-title":"Preparation of medicinal plants: Basic extraction and fractionation procedures for experimental purposes","volume":"12","author":"Abubakar","year":"2020","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_52","first-page":"492","article-title":"Antidiabetic effect of aqueous extract of Medicago sativa with enhanced histopathology of Pancreas in alloxan induced diabetic rats","volume":"15","author":"Khalaf","year":"2021","journal-title":"Pak. J. Med. Health Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"245","DOI":"10.36348\/sjbr.2025.v10i07.002","article-title":"Phytochemical Estimation and In Vitro Antihyperglycemic and Antioxidant Study of Leaf Extract of Wrightia tinctoria (Roxb) R.BR","volume":"10","author":"Baskaran","year":"2025","journal-title":"Saudi J. Biomed. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.eurpolymj.2004.10.037","article-title":"Characterization of ligno-cellulosic seed fibre from Wrightia Tinctoria plant for textile applications\u2014An exploratory investigation","volume":"41","author":"Subramanian","year":"2005","journal-title":"Eur. Polym. J."},{"key":"ref_55","first-page":"199","article-title":"Extraction and isolation of bioactive compounds from a therapeutic medicinal plant-Wrightia tinctoria (Roxb.) R. Br","volume":"11","author":"Hemavathy","year":"2019","journal-title":"Int. J. Pharmacogn. Phytochem. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8792\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:28:21Z","timestamp":1791970101000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8792"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":55,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198792"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198792","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]}}}