{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:56:22Z","timestamp":1793058982804,"version":"4.5.0"},"reference-count":261,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open Fund of Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine","award":["KLRCCM2503"],"award-info":[{"award-number":["KLRCCM2503"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Drosophila melanogaster shares approximately 75% of human disease-related genes and possesses sophisticated genetic toolkits, including GAL4\/UAS, CRISPR-Cas9, and RNA interference (RNAi), making it a rapid, cost-effective, and genetically tractable in vivo platform for natural products (NPs) discovery. This review systematically summarizes the modeling strategies, pathological mechanisms, and therapeutic applications of Drosophila models for six major human diseases, including type 2 diabetes, nephrolithiasis, inflammatory bowel disease, cancer, Alzheimer\u2019s disease, and Parkinson\u2019s disease. Cross-disease analysis identifies five evolutionarily conserved signaling networks\u2014IIS\/PI3K\/Akt\/FOXO, JNK\/JAK\/STAT, Nrf2\/Keap1, mTOR\/TORC1, and IMD\/Toll\u2014as common molecular targets of bioactive NPs, providing a unified mechanistic framework for understanding their multi-target pharmacological activities and broad therapeutic potential. Critically, we propose a generalizable integrated stepwise pipeline: high-throughput fly screening of crude extracts, bioassay-guided isolation of active monomers, genetic mechanistic dissection via RNAi and mutant rescue, and layered validation in human cells and selective mammalian models. This pipeline addresses key challenges in NPs research, including the identification of bioactive constituents and mechanistic validation, while improving screening efficiency and translational potential. Overall, this review establishes a multi-disease-applicable framework linking disease modeling, conserved signaling mechanisms, and translational pharmacology, providing practical guidance for future mechanism-driven NP discovery and preclinical development using Drosophila. By leveraging Drosophila genetics to bridge evolutionary conservation and human pathology, this framework offers a powerful, paradigm-shifting strategy to accelerate mechanism-driven NP discovery and preclinical development.<\/jats:p>","DOI":"10.3390\/biology15171447","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:03:41Z","timestamp":1787558621000},"page":"1447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Drosophila melanogaster Models for Natural Product Discovery: Cross-Disease Conserved Signaling Networks and a Generalizable Translational Pipeline"],"prefix":"10.3390","volume":"15","author":[{"given":"Ying","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"He","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxiang","family":"Chang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China"},{"name":"Neurocritical Care Medicine Innovation Center, Ministry of Education, Tianjin University, Tianjin 300072, China"},{"name":"International Joint Research Centre for Molecular Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1097\/JS9.0000000000002260","article-title":"Burden and attributable risk factors of non-communicable diseases and subtypes in 204 countries and territories, 1990\u20132021: A systematic analysis for the global burden of disease study 2021","volume":"111","author":"Li","year":"2025","journal-title":"Int. J. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100125","DOI":"10.1016\/j.pharmr.2026.100125","article-title":"Emerging natural products against obesity and metabolic dysfunction-associated steatotic liver disease\/metabolic dysfunction-associated steatohepatitis: Direct target discovery and mechanistic insights","volume":"78","author":"Hu","year":"2026","journal-title":"Pharmacol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cai, Z., Wang, S., and Li, J. (2021). Treatment of Inflammatory Bowel Disease: A Comprehensive Review. Front. Med., 8.","DOI":"10.3389\/fmed.2021.765474"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2200182","DOI":"10.1002\/ardp.202200182","article-title":"Therapeutic management of arthritis: A review on structural and target-based approaches","volume":"355","author":"Mahore","year":"2022","journal-title":"Arch. Der Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: An expanding universe","volume":"186","author":"Blasco","year":"2023","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e10026","DOI":"10.1002\/ggn2.10026","article-title":"Aging mechanisms\u2014A perspective mostly from Drosophila","volume":"1","author":"Tsurumi","year":"2020","journal-title":"Genet. Genom. Next"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1007\/s11101-025-10194-7","article-title":"Medicinal plants and human health: A comprehensive review of bioactive compounds, therapeutic effects, and applications","volume":"25","author":"Latif","year":"2026","journal-title":"Phytochem. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Scannell, J.W., and Bosley, J. (2016). When Quality Beats Quantity: Decision Theory, Drug Discovery, and the Reproducibility Crisis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147215"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1124\/pr.110.003293","article-title":"Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery","volume":"63","author":"Pandey","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Panossian, A. (2023). Challenges in phytotherapy research. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1199516"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: Advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.jfutfo.2022.08.002","article-title":"Food-derived bioactive peptides: Production, biological activities, opportunities and challenges","volume":"2","author":"Ye","year":"2022","journal-title":"J. Future Foods"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, A.C., Pinto, A.R., Cima, A., Olo-Fontinha, E., Martins, J.C.L., Garcia, J., Lemos, A., Saavedra, M.J., Pintado, M.M., and Alves, M.J. (2026). Plant-Derived Bioactive Compounds: One Health Perspective. Appl. Sci., 16.","DOI":"10.3390\/app16010327"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.chmed.2026.05.003","article-title":"Multi-pathway targeting by natural products in chronic respiratory diseases: Opportunities, challenges, and future perspectives","volume":"18","author":"Lin","year":"2026","journal-title":"Chin. Herbal. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13593","DOI":"10.1002\/ece3.7003","article-title":"Natural history of model organisms: The secret (group) life of Drosophila melanogaster larvae and why it matters to developmental ecology","volume":"10","author":"Morimoto","year":"2020","journal-title":"Ecol. Evol."},{"key":"ref_17","first-page":"1","article-title":"Phylogeny of the Genus Drosophila","volume":"209","author":"Desalle","year":"2018","journal-title":"Genetics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1101\/gr.169101","article-title":"A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster","volume":"11","author":"Reiter","year":"2001","journal-title":"Genome Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1242\/dmm.023762","article-title":"Drosophila tools and assays for the study of human diseases","volume":"9","author":"Ugur","year":"2016","journal-title":"Dis. Model. Mech."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nrn2839","article-title":"100 years of Drosophila research and its impact on vertebrate neuroscience: A history lesson for the future","volume":"11","author":"Bellen","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Moraes, K.C.M., and Montagne, J. (2021). Drosophila melanogaster: A Powerful Tiny Animal Model for the Study of Metabolic Hepatic Diseases. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.728407"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"eabg4336","DOI":"10.1126\/sciadv.abg4336","article-title":"What fuels the fly: Energy metabolism in Drosophila and its application to the study of obesity and diabetes","volume":"7","author":"Chatterjee","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1007\/s11427-017-9029-9","article-title":"Genome editing in Drosophila melanogaster: From basic genome engineering to the multipurpose CRISPR-Cas9 system","volume":"60","author":"Ren","year":"2017","journal-title":"Sci. China Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lopez-Ortiz, C., Gracia-Rodriguez, C., Belcher, S., Flores-Iga, G., Das, A., Nimmakayala, P., Balagurusamy, N., and Reddy, U.K. (2023). Drosophila melanogaster as a Translational Model System to Explore the Impact of Phytochemicals on Human Health. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202308.0667.v1"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mudjahid, M., Latada, N.P., Ophinni, Y., and Nainu, F. (2025). Drosophila-based screening of herbal compounds targeting FOXO signaling pathway in type 2 diabetes mellitus. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1621414"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"157123","DOI":"10.1016\/j.phymed.2025.157123","article-title":"Unlocking nature\u2019s medicine cabinet through Drosophila-Driven exploration","volume":"146","author":"Sheng","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2420453","DOI":"10.1080\/19336934.2024.2420453","article-title":"Exploring the versatility of Drosophila melanogaster as a model organism in biomedical research: A comprehensive review","volume":"19","author":"Aja","year":"2025","journal-title":"Fly"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"186","DOI":"10.17305\/bb.2025.12656","article-title":"Drosophila melanogaster models for investigating inflammatory bowel disease: Methods, pathology, mechanisms, and therapeutic approaches","volume":"26","author":"Li","year":"2025","journal-title":"Biomol. Biomed."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/s11033-026-11844-5","article-title":"Modeling human neurodegenerative disorders in Drosophila: Strategies and translational opportunities","volume":"53","author":"Mohamed","year":"2026","journal-title":"Mol. Biol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xiu, M., Wang, Y., Yang, D., Zhang, X., Dai, Y., Liu, Y., Lin, X., Li, B., and He, J. (2022). Using Drosophila melanogaster as a suitable platform for drug discovery from natural products in inflammatory bowel disease. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1072715"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1039\/C9MD00099B","article-title":"Using Drosophila as a platform for drug discovery from natural products in Parkinson\u2019s disease","volume":"10","author":"Maitra","year":"2019","journal-title":"Medchemcomm"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.2337\/dc13-2112","article-title":"The diabetes control and complications trial\/epidemiology of diabetes interventions and complications study at 30 years: Overview","volume":"37","author":"Nathan","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12933-018-0728-6","article-title":"Prevalence of cardiovascular disease in type 2 diabetes: A systematic literature review of scientific evidence from across the world in 2007\u20132017","volume":"17","author":"Einarson","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4538","DOI":"10.1073\/pnas.1814711116","article-title":"NOTCH1 signaling induces pathological vascular permeability in diabetic retinopathy","volume":"116","author":"Miloudi","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cell.2020.08.009","article-title":"Targeting Mitochondria-Located circRNA SCAR Alleviates NASH via Reducing mROS Output","volume":"183","author":"Zhao","year":"2020","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1126\/science.aay0542","article-title":"An AMPK-caspase-6 axis controls liver damage in nonalcoholic steatohepatitis","volume":"367","author":"Zhao","year":"2020","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e2100275","DOI":"10.1002\/advs.202100275","article-title":"Emerging Targets in Type 2 Diabetes and Diabetic Complications","volume":"8","author":"Demir","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1056\/NEJM199309303291401","article-title":"The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus","volume":"329","author":"Nathan","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1001\/jama.2025.5956","article-title":"Diagnosis and Treatment of Type 2 Diabetes in Adults: A Review","volume":"334","author":"Kalyani","year":"2025","journal-title":"JAMA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41574-020-0355-7","article-title":"Pancreatic \u03b2-cells in type 1 and type 2 diabetes mellitus: Different pathways to failure","volume":"16","author":"Eizirik","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Elkhalifa, A.M.E., Nazar, M., Ali, S.I., Khursheed, I., Taifa, S., Ahmad Mir, M., Shah, I.H., Malik, M., Ramzan, Z., and Ahad, S. (2024). Novel Therapeutic Agents for Management of Diabetes Mellitus: A Hope for Drug Designing against Diabetes Mellitus. Life, 14.","DOI":"10.3390\/life14010099"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1126\/science.1070058","article-title":"Ablation of insulin-producing neurons in flies: Growth and diabetic phenotypes","volume":"296","author":"Rulifson","year":"2002","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Liguori, F., Mascolo, E., and Vern\u00ec, F. (2021). The Genetics of Diabetes: What We Can Learn from Drosophila. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011295"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"166749","DOI":"10.1016\/j.bbadis.2023.166749","article-title":"Effect of time-restricted feeding on high-fat diet-induced metabolic dysfunction in Drosophila melanogaster","volume":"1869","author":"Quenti","year":"2023","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"RP98514","DOI":"10.7554\/eLife.98514","article-title":"Nutritional state-dependent modulation of insulin-producing cells in Drosophila","volume":"13","author":"Bisen","year":"2025","journal-title":"eLife"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Baenas, N., and Wagner, A.E. (2022). Drosophila melanogaster as a Model Organism for Obesity and Type-2 Diabetes Mellitus by Applying High-Sugar and High-Fat Diets. Biomolecules, 12.","DOI":"10.3390\/biom12020307"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"30265","DOI":"10.1038\/srep30265","article-title":"High fat diet-induced TGF-\u03b2\/Gbb signaling provokes insulin resistance through the tribbles expression","volume":"6","author":"Hong","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Singh, R., Gholipourmalekabadi, M., and Shafikhani, S.H. (2024). Animal models for type 1 and type 2 diabetes: Advantages and limitations. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1359685"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fang, J.Y., Lin, C.H., Huang, T.H., and Chuang, S.Y. (2019). In Vivo Rodent Models of Type 2 Diabetes and Their Usefulness for Evaluating Flavonoid Bioactivity. Nutrients, 11.","DOI":"10.3390\/nu11030530"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1126\/science.287.5461.2185","article-title":"The Genome Sequence of Drosophila melanogaster","volume":"287","author":"Adams","year":"2000","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.ygcen.2014.11.021","article-title":"Insulin\/IGF signaling and its regulation in Drosophila","volume":"221","author":"Liu","year":"2015","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Skowronek, P., W\u00f3jcik, \u0141., and Strachecka, A. (2021). Fat Body\u2014Multifunctional Insect Tissue. Insects, 12.","DOI":"10.3390\/insects12060547"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zeng, Y., Yang, Y., Zhu, Y., Xu, P., Cheong, C., Zhao, Y.J., and Baeg, G.H. (2026). Altered mitochondrial functionality in metabolic disorders: Insights from Drosophila studies. Front. Endocrinol., 17.","DOI":"10.3389\/fendo.2026.1817121"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Vilcinskas, A. (2013). Drosophila as a Model to Study Metabolic Disorders. Yellow Biotechnology I: Insect Biotechnologie in Drug Discovery and Preclinical Research, Springer.","DOI":"10.1007\/978-3-642-39863-6"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/eea.12981","article-title":"Drosophila insulin-like peptides: From expression to functions\u2014A review","volume":"169","author":"Semaniuk","year":"2021","journal-title":"Entomol. Exp. Appl."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.cmet.2010.09.014","article-title":"High-Fat-Diet-Induced Obesity and Heart Dysfunction Are Regulated by the TOR Pathway in Drosophila","volume":"12","author":"Birse","year":"2010","journal-title":"Cell Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/abbs\/gms105","article-title":"Lipid metabolism in Drosophila: Development and disease","volume":"45","author":"Liu","year":"2013","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4531","DOI":"10.1038\/s41598-018-36060-5","article-title":"Dynamic mitochondrial responses to a high-fat diet in Drosophila melanogaster","volume":"9","author":"Cormier","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"100507","DOI":"10.1016\/j.prmcm.2024.100507","article-title":"Pharmacological effects of Berberine\u2014A Chinese medicine, against xenobiotics toxicity","volume":"13","author":"Phogat","year":"2024","journal-title":"Pharmacol. Res.-Mod. Chin. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.tem.2023.10.002","article-title":"Mechanisms of hepatic fatty acid oxidation and ketogenesis during fasting","volume":"35","author":"Ruppert","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Yue, T., Jiang, M., Onuki, K., Itoh, M., and Tonoki, A. (2025). High-fat diet impairs intermediate-term memory by autophagic-lysosomal dysfunction in Drosophila. PLoS Genet., 21.","DOI":"10.1371\/journal.pgen.1011818"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/jbiol72","article-title":"Imp-L2, a putative homolog of vertebrate IGF-binding protein 7, counteracts insulin signaling in Drosophila and is essential for starvation resistance","volume":"7","author":"Honegger","year":"2008","journal-title":"J. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41586-023-06466-x","article-title":"Gut microbial carbohydrate metabolism contributes to insulin resistance","volume":"621","author":"Takeuchi","year":"2023","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"105017","DOI":"10.1016\/j.yexmp.2025.105017","article-title":"Understanding diabetes and its complications through the lens of Drosophila","volume":"145","author":"Bevinakoppamath","year":"2026","journal-title":"Exp. Mol. Pathol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/S0960-9822(02)01043-6","article-title":"Nutrient-Dependent Expression of Insulin-like Peptides from Neuroendocrine Cells in the CNS Contributes to Growth Regulation in Drosophila","volume":"12","author":"Ikeya","year":"2002","journal-title":"Curr. Biol."},{"key":"ref_66","first-page":"1417528","article-title":"Drosophila melanogaster as a Model for Diabetes Type 2 Progression","volume":"2018","author":"Salceda","year":"2018","journal-title":"BioMed. Res. Int."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/S0092-8674(00)80799-0","article-title":"Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4","volume":"97","author":"Oldham","year":"1999","journal-title":"Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1007\/s00125-025-06501-8","article-title":"Identification of SEC16B as a novel regulator of glucose homeostasis","volume":"68","author":"Zhang","year":"2025","journal-title":"Diabetologia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.jtcme.2024.01.010","article-title":"Atractylodes macrocephala Koidz. and Cuscuta chinensis Lam. extract relieves insulin resistance via PI3K\/Akt signalling in diabetic Drosophila","volume":"14","author":"Li","year":"2024","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Cao, X., La, X., Zhang, B., Wang, Z., Li, Y., Bo, Y., Chang, H., Gao, X., Tian, C., and Wu, C. (2022). Sanghuang Tongxie Formula Ameliorates Insulin Resistance in Drosophila Through Regulating PI3K\/Akt Signaling. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.874180"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"109041","DOI":"10.1016\/j.cbpc.2021.109041","article-title":"Modulatory effect of Artocarpus camansi on ILP-2, InR, and Imp-L2 genes of sucrose\u2013induced diabetes mellitus in Drosophila melanogaster","volume":"246","author":"Saliu","year":"2021","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_72","first-page":"663","article-title":"Antidiabetes study of Spondias mombin (Linn) stem bark fractions in high-sucrose diet-induced diabetes in Drosophila melanogaster","volume":"18","author":"Omoboyowa","year":"2023","journal-title":"J. Taibah Univ. Med. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1080\/13813455.2020.1820525","article-title":"Biochanin A, a soy isoflavone, diminishes insulin resistance by modulating insulin-signalling pathway in high-fat diet-induced diabetic mice","volume":"129","author":"Arjunan","year":"2020","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Zhang, N., Zhang, W., Guo, X., Liu, J., Li, S., Zhang, H., and Fan, B. (2022). Genistein protects against hyperglycemia and fatty liver disease in diet-induced prediabetes mice via activating hepatic insulin signaling pathway. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.1072044"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Yang, X., Dai, K., and Wang, S. (2025). Genistein Enhances GLUT4 Expression and Translocation in the Gastrocnemius Muscle and Improves Systemic Glucose Metabolism in Ovariectomized Mice. Nutrients, 17.","DOI":"10.3390\/nu17172811"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"L\u00fcersen, K., Fischer, A., Bauer, I., Huebbe, P., Uekaji, Y., Chikamoto, K., Nakata, D., Hiramatsu, N., Terao, K., and Rimbach, G. (2023). Soy Extract, Rich in Hydroxylated Isoflavones, Exhibits Antidiabetic Properties In Vitro and in Drosophila melanogaster In Vivo. Nutrients, 15.","DOI":"10.3390\/nu15061392"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"107265","DOI":"10.1016\/j.fbio.2025.107265","article-title":"Crocin alleviates high-sugar diet-induced type 2 diabetes model in Drosophila","volume":"71","author":"Yu","year":"2025","journal-title":"Food Biosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"116760","DOI":"10.1016\/j.jep.2023.116760","article-title":"The water extract of Potentilla discolor Bunge (PDW) ameliorates high-sugar diet-induced type II diabetes model in Drosophila melanogaster via JAK\/STAT signaling","volume":"316","author":"Li","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"747","DOI":"10.2147\/DDDT.S439876","article-title":"Mechanisms of Action of Potentilla discolor Bunge in Type 2 Diabetes Mellitus Based on Network Pharmacology and Experimental Verification in Drosophila","volume":"18","author":"Li","year":"2024","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"166901","DOI":"10.1016\/j.bbadis.2023.166901","article-title":"Acetobacter and lactobacillus alleviate the symptom of insulin resistance by blocking the JNK-JAK\/STAT pathway in Drosophila melanogaster","volume":"1870","author":"Meng","year":"2024","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3466","DOI":"10.1038\/s44318-024-00162-w","article-title":"Gut microbiota metabolite tyramine ameliorates high-fat diet-induced insulin resistance via increased Ca2+ signaling","volume":"43","author":"Ma","year":"2024","journal-title":"Embo J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"760","DOI":"10.14336\/AD.2016.0620","article-title":"Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging-Related Diseases via Anti-Oxidation and AMPK Activation","volume":"8","author":"Xu","year":"2017","journal-title":"Aging Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1002\/jez.2812","article-title":"Drosophila melanogaster as a model organism for diabetes II treatment by the ethyl acetate fraction of Atriplex halimus L.","volume":"341","author":"Montaser","year":"2024","journal-title":"J. Exp. Zool. A Ecol. Integr. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41420-023-01681-x","article-title":"The role of sphingosine-1-phosphate in autophagy and related disorders","volume":"9","author":"Xiao","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ebiom.2018.12.038","article-title":"S1P\/S1PR3 axis promotes aerobic glycolysis by YAP\/c-MYC\/PGAM1 axis in osteosarcoma","volume":"40","author":"Shen","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_86","first-page":"2977","article-title":"C16-ceramide and sphingosine 1-phosphate\/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation","volume":"40","author":"Park","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"117248","DOI":"10.1016\/j.jep.2023.117248","article-title":"Lanhuashen stimulates the positive cross-regulation mediated by the S1P axis to ameliorate the disorder of glucolipid metabolism induced by the high sucrose diet in Drosophila melanogaster","volume":"319","author":"Yu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Barchetta, I., Cimini, F.A., Dule, S., and Cavallo, M.G. (2022). Dipeptidyl Peptidase 4 (DPP4) as A Novel Adipokine: Role in Metabolism and Fat Homeostasis. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092306"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Lagunas-Rangel, F.A., Liao, S., Williams, M.J., Trukhan, V., Fredriksson, R., and Schi\u00f6th, H.B. (2023). Drosophila as a Rapid Screening Model to Evaluate the Hypoglycemic Effects of Dipeptidyl Peptidase 4 (DPP4) Inhibitors: High Evolutionary Conservation of DPP4. Biomedicines, 11.","DOI":"10.3390\/biomedicines11113032"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"116487","DOI":"10.1016\/j.foodres.2025.116487","article-title":"Exploration of novel dipeptidyl peptidase-IV inhibitory tetrapeptide from walnut (Juglans sigillata) protein and its effect on diabetes-like phenotypes induced by high-sugar diet in Drosophila melanogaster","volume":"211","author":"Chen","year":"2025","journal-title":"Food Res. Int."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Wang, M., Mao, H., Chen, J., Qi, L., and Wang, J. (2022). Ameliorative effect of bayberry leaves proanthocyanidins on high sugar diet induced Drosophila melanogaster. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1008580"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1242\/dmm.007948","article-title":"A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila","volume":"4","author":"Musselman","year":"2011","journal-title":"Dis. Model. Mech."},{"key":"ref_93","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_94","doi-asserted-by":"crossref","first-page":"29834","DOI":"10.1038\/s41598-025-13246-2","article-title":"In Silico evaluation of phytoconstituents from Carica Papaya and its anti-hyperglycemic activities on high sucrose-induced oxidative stress in Drosophila melanogaster","volume":"15","author":"Oloyede","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Dechakhamphu, A., Wongchum, N., Chumroenphat, T., Tanomtong, A., Pinlaor, S., and Siriamornpun, S. (2023). In Vitro and In Vivo Evaluation for Antioxidant and Anti-Diabetic Properties of Cyperus rotundus L. Kombucha. Foods, 12.","DOI":"10.20944\/preprints202310.1201.v1"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Dong, Z., Sun, Y., Wei, G., Li, S., and Zhao, Z. (2019). Ergosterol Ameliorates Diabetic Nephropathy by Attenuating Mesangial Cell Proliferation and Extracellular Matrix Deposition via the TGF-\u03b21\/Smad2 Signaling Pathway. Nutrients, 11.","DOI":"10.3390\/nu11020483"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e05469","DOI":"10.1002\/advs.202505469","article-title":"Gut Microbial Genetic Variation Prolongs Host Healthy Longevity and Remodels Metabolome and Proteome in Drosophila melanogaster","volume":"12","author":"Wang","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Youn, I., Piao, D., Park, J., Ock, S.A., Han, S., Han, A.-R., Shin, S., and Seo, E.K. (2024). Anti-Obesity Activities of the Compounds from Perilla frutescens var. acuta and Chemical Profiling of the Extract. Molecules, 29.","DOI":"10.3390\/molecules29112465"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bbrc.2022.07.116","article-title":"Dietary supplementation with perillartine ameliorates lipid metabolism disorder induced by a high-fat diet in broiler chickens","volume":"625","author":"Xiao","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Plaza-Diaz, J., Pastor-Villaescusa, B., Rueda-Robles, A., Abadia-Molina, F., and Ruiz-Ojeda, F.J. (2020). Plausible Biological Interactions of Low- and Non-Calorie Sweeteners with the Intestinal Microbiota: An Update of Recent Studies. Nutrients, 12.","DOI":"10.3390\/nu12041153"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"20150469","DOI":"10.1098\/rsbl.2015.0469","article-title":"Consumption of dietary sugar by gut bacteria determines Drosophila lipid content","volume":"11","author":"Huang","year":"2015","journal-title":"Biol. Lett."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1002\/fft2.147","article-title":"Effects of non-caloric artificial sweeteners on na\u00efve and dextran sodium sulfate-exposed Drosophila melanogaster","volume":"3","author":"Hubrecht","year":"2022","journal-title":"Food Front."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"115298","DOI":"10.1016\/j.biopha.2023.115298","article-title":"Neuroprotective role of plumbagin on eye damage induced by high-sucrose diet in adult fruit fly Drosophila melanogaster","volume":"166","author":"Catalani","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"14052","DOI":"10.1021\/acsomega.4c11062","article-title":"In Silico and In Vivo Investigation of the Anti-Hyperglycemic Effects of Caffeic Acid","volume":"10","author":"Ratnawati","year":"2025","journal-title":"ACS Omega"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.fct.2012.09.021","article-title":"A review on antioxidants, prooxidants and related controversy: Natural and synthetic compounds, screening and analysis methodologies and future perspectives","volume":"51","author":"Carocho","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1055\/s-0042-100810","article-title":"The Steroidal Glycoalkaloids from Solanaceae: Toxic Effect, Antitumour Activity and Mechanism of Action","volume":"82","author":"Tomsik","year":"2016","journal-title":"Planta Medica"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Pitchakarn, P., Inthachat, W., Karinchai, J., and Temviriyanukul, P. (2021). Human Hazard Assessment Using Drosophila Wing Spot Test as an Alternative In Vivo Model for Genotoxicity Testing\u2014A Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189932"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"ieag020","DOI":"10.1093\/jisesa\/ieag020","article-title":"Antioxidant enzymes, oxidative stress, and physiological aging markers in Drosophila melanogaster (Diptera: Drosophilidae): A systematic review with translational perspectives","volume":"26","year":"2026","journal-title":"J. Insect Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1146\/annurev.arplant.56.032604.144106","article-title":"Calcium oxalate in Plants: Formation and Function","volume":"56","author":"Franceschi","year":"2005","journal-title":"Annu. Rev. Plant Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"F1555","DOI":"10.1152\/ajprenal.00074.2012","article-title":"In vivo Drosophilia genetic model for calcium oxalate nephrolithiasis","volume":"303","author":"Hirata","year":"2012","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e09232","DOI":"10.1016\/j.heliyon.2022.e09232","article-title":"The fruit fly kidney stone models and their application in drug development","volume":"8","author":"Wang","year":"2022","journal-title":"Heliyon"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e22057","DOI":"10.1002\/arch.22057","article-title":"Insect cuticle and insecticide development","volume":"114","author":"Ren","year":"2023","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"117968","DOI":"10.1016\/j.jep.2024.117968","article-title":"The anti-urolithiasis activity and safety of strangury-relieving herbs: A comparative study based on fruit fly kidney stone model","volume":"326","author":"Lu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Yang, H., Male, M., Li, Y., Wang, N., Zhao, C., Jin, S., Hu, J., Chen, Z., Ye, Z., and Xu, H. (2018). Efficacy of Hydroxy-L-proline (HYP) analogs in the treatment of primary hyperoxaluria in Drosophila melanogaster. BMC Nephrol., 19.","DOI":"10.1186\/s12882-018-0980-8"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.12659\/MSM.913637","article-title":"Hydroxycitric Acid Tripotassium Inhibits Calcium Oxalate Crystal Formation in the Drosophila melanogaster Model of Hyperoxaluria","volume":"25","author":"Han","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0140-6736(06)68071-9","article-title":"Kidney stones: Pathophysiology and medical management","volume":"367","author":"Moe","year":"2006","journal-title":"Lancet"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00240-004-0437-3","article-title":"The impact of dietary oxalate on kidney stone formation","volume":"32","author":"Holmes","year":"2004","journal-title":"Urol. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"156145","DOI":"10.1016\/j.phymed.2024.156145","article-title":"Kukoamine A alleviates nephrolithiasis by inhibiting endogenous oxalate synthesis via the IL-6\/JAK\/STAT3\/DAO signaling pathway","volume":"135","author":"Ju","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_119","first-page":"1","article-title":"The Medicine-Food Homology Fruit Gouqi (Lycium barbarum L.) Mitigates Kidney Stone via Multiple Bioactivities","volume":"21","author":"Zhang","year":"2026","journal-title":"Nat. Product. Commun."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"636","DOI":"10.3390\/pathogens2040636","article-title":"The metabolic and ecological interactions of oxalate-degrading bacteria in the Mammalian gut","volume":"2","author":"Miller","year":"2013","journal-title":"Pathogens"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2546158","DOI":"10.1080\/19490976.2025.2546158","article-title":"Gut microbiota-regulated unconjugated bilirubin metabolism drives renal calcium oxalate crystal deposition","volume":"17","author":"Li","year":"2025","journal-title":"Gut Microbes"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.2741\/1347","article-title":"Modulators of urinary stone formation","volume":"9","author":"Khan","year":"2004","journal-title":"Front. Biosci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"dmm035873","DOI":"10.1242\/dmm.035873","article-title":"Drosophila melanogaster as a function-based high-throughput screening model for antinephrolithiasis agents in kidney stone patients","volume":"11","author":"Ali","year":"2018","journal-title":"Dis. Model. Mech."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.msec.2015.07.032","article-title":"Preparation, characterization, and in vitro cytotoxicity of COM and COD crystals with various sizes","volume":"57","author":"Sun","year":"2015","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"119777","DOI":"10.1016\/j.carbpol.2022.119777","article-title":"Aspidopterys obcordata vine inulin fructan affects urolithiasis by modifying calcium oxalate crystallization","volume":"294","author":"Sun","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Palierse, E., Przybylski, C., Brouri, D., Jolivalt, C., and Coradin, T. (2020). Interactions of Calcium with Chlorogenic and Rosmarinic Acids: An Experimental and Theoretical Approach. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21144948"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Hong, S.-Y., and Qin, B.-L. (2023). The Protective Role of Dietary Polyphenols in Urolithiasis: Insights into Antioxidant Effects and Mechanisms of Action. Nutrients, 15.","DOI":"10.3390\/nu15173753"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"119846","DOI":"10.1016\/j.jep.2025.119846","article-title":"Streamlined strategy for discovering active compounds for nephrolithiasis treatment from herbal medicines using the fruit fly model","volume":"348","author":"Ren","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1111\/j.1523-1755.2004.00963.x","article-title":"Mitochondrial dysfunction is a primary event in renal cell oxalate toxicity","volume":"66","author":"Cao","year":"2004","journal-title":"Kidney Int."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1080\/10715762.2020.1751835","article-title":"Oxidative stress and endoplasmic stress in calcium oxalate stone disease: The chicken or the egg?","volume":"54","author":"Albert","year":"2020","journal-title":"Free Radic. Res."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Chen, S.J., Dalanbaatar, S., Chen, H.Y., Wang, S.J., Lin, W.Y., Liu, P.L., Tsai, M.Y., Chen, D.C., Chen, Y.H., and Chen, W.C. (2022). Astragalus membranaceus Extract Prevents Calcium Oxalate Crystallization and Extends Lifespan in a Drosophila Urolithiasis Model. Life, 12.","DOI":"10.3390\/life12081250"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"110732","DOI":"10.1016\/j.msec.2020.110732","article-title":"Preparation and characterization of selenized Astragalus polysaccharide and its inhibitory effect on kidney stones","volume":"110","author":"Huang","year":"2020","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_133","first-page":"43","article-title":"Astragalus membranaceus reduces free radical-mediated injury to renal tubules in rabbits receiving high-energy shock waves","volume":"118","author":"Sheng","year":"2005","journal-title":"Chin. Med. J."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"868","DOI":"10.14336\/AD.2017.0816","article-title":"Anti-Aging Implications of Astragalus Membranaceus (Huangqi): A Well-Known Chinese Tonic","volume":"8","author":"Liu","year":"2017","journal-title":"Aging Dis."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"100220","DOI":"10.1016\/j.prmcm.2023.100220","article-title":"Drosophila model and network pharmacology to explore novel targets and novel active components of chinese traditional medications for treating kidney stones","volume":"6","author":"Zhang","year":"2023","journal-title":"Pharmacol. Res.-Mod. Chin. Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.bbrc.2019.01.123","article-title":"Ascl2 facilitates IL-10 production in Th17 cells to restrain their pathogenicity in inflammatory bowel disease","volume":"510","author":"Yi","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.2147\/DDDT.S499284","article-title":"Caffeic Acid Protects Against Ulcerative Colitis via Inhibiting Mitochondrial Apoptosis and Immune Overactivation in Drosophila","volume":"19","author":"Xiu","year":"2025","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1074\/jbc.C200673200","article-title":"Host Recognition of Bacterial Muramyl Dipeptide Mediated through NOD2: Implications for Crohn\u2032s Disease","volume":"278","author":"Inohara","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Zeng, C., Liu, F., Huang, Y., Liang, Q., He, X., Li, L., and Xie, Y. (2024). Drosophila: An Important Model for Exploring the Pathways of Inflammatory Bowel Disease (IBD) in the Intestinal Tract. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252312742"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Zhang, G., Gu, Y., and Dai, X. (2022). Protective Effect of Bilberry Anthocyanin Extracts on Dextran Sulfate Sodium-Induced Intestinal Damage in Drosophila melanogaster. Nutrients, 14.","DOI":"10.3390\/nu14142875"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Yang, S., Li, X., Xiu, M., Dai, Y., Wan, S., Shi, Y., Liu, Y., and He, J. (2022). Flos puerariae ameliorates the intestinal inflammation of Drosophila via modulating the Nrf2\/Keap1, JAK-STAT and Wnt signaling. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.893758"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Madi, J.R., Outa, A.A., Ghannam, M., Hussein, H.M., Shehab, M., Hasan, Z.A.K.H., Fayad, A.A., Shirinian, M., and Rahal, E.A. (2021). Drosophila melanogaster as a Model System to Assess the Effect of Epstein-Barr Virus DNA on Inflammatory Gut Diseases. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.586930"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"114265","DOI":"10.1016\/j.biopha.2023.114265","article-title":"Exposure to cytarabine causes side effects on adult development and physiology and induces intestinal damage via apoptosis in Drosophila","volume":"159","author":"Han","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_144","first-page":"3990","article-title":"Drosophila Atg16 promotes enteroendocrine cell differentiation via regulation of intestinal Slit\/Robo signaling","volume":"144","author":"Nagy","year":"2017","journal-title":"Development"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Kim, H., Yi, X., Xue, H., Yue, G., Zhu, J., Eh, T., Wang, S., and Jin, L.H. (2024). Extracts of Hylotelephiumerythrostictum (miq.) H. Ohba ameliorate intestinal injury by scavenging ROS and inhibiting multiple signaling pathways in Drosophila. BMC Complement. Med. Ther., 24.","DOI":"10.1186\/s12906-024-04686-w"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Lee, S.H., Hwang, D., Lee, J.W., Goo, T.W., and Yun, E.Y. (2025). The Identification of a Glucuronyltransferase-Related Gene, GlcAT-S, with Putative Mucus Protection and Anti-Inflammatory Effects from Gut-Damaged Drosophila by Dextran Sulfate Sodium (DSS). Biology, 14.","DOI":"10.20944\/preprints202502.2339.v1"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.2147\/JIR.S500892","article-title":"Caffeic Acid Alleviates Chronic Sleep Deprivation-Induced Intestinal Damage by Inhibiting the IMD Pathway in Drosophila","volume":"18","author":"Yang","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Xu, Y., Li, X., Miao, Y., Liu, X., Zang, X., Meng, Q., Li, Y., Yang, F., Yuchi, Z., and Wang, Y. (2026). Xuanfei Baidu decoction alleviates intestinal inflammation and modulates microbiota distribution by suppressing IMD\/NF-\u03baB and JNK signaling pathways. Front. Microbiol., 17.","DOI":"10.3389\/fmicb.2026.1853715"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"He, J., Li, X., Yang, S., Shi, Y., Dai, Y., Han, S., Wang, Y., Lin, X., Wei, B., and Liu, Y. (2022). Protective effect of astragalus membranaceus and its bioactive compounds against the intestinal inflammation in Drosophila. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1019594"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"6925","DOI":"10.2147\/DDDT.S525366","article-title":"Danggui Buxue Decoction Alleviates Acute Hypoxia-Induced Sleep Disorders: Insights from In Vivo and In Silico Analyses","volume":"19","author":"Zhou","year":"2025","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3892\/etm.2023.12068","article-title":"Effect and mechanism of total ginsenosides repairing SDS-induced Drosophila enteritis model based on MAPK pathway","volume":"26","author":"Su","year":"2023","journal-title":"Exp. Ther. Med."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Yan, L., Guo, X., Zhou, J., Zhu, Y., Zhang, Z., and Chen, H. (2022). Quercetin Prevents Intestinal Stem Cell Aging via Scavenging ROS and Inhibiting Insulin Signaling in Drosophila. Antioxidants, 12.","DOI":"10.3390\/antiox12010059"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Sheng, X., Zhu, Y., Zhou, J., Yan, L., Du, G., Liu, Z., and Chen, H. (2021). Antioxidant Effects of Caffeic Acid Lead to Protection of Drosophila Intestinal Stem Cell Aging. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.735483"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Yan, L., Zhou, J., Yuan, L., Ye, J., Zhao, X., Ren, G., and Chen, H. (2023). Silibinin alleviates intestinal inflammation via inhibiting JNK signaling in Drosophila. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1246960"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e743","DOI":"10.52225\/narra.v4i1.743","article-title":"Curcumin-mediated alleviation of dextran-induced leaky gut in Drosophila melanogaster","volume":"4","author":"Khaerani","year":"2024","journal-title":"Narra J."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"e70113","DOI":"10.1002\/fsn3.70113","article-title":"Thymoquinone Ameliorates Gut Epithelial Injury by Suppressing the JNK Signaling Pathway Based on Its Anti-Oxidant Property","volume":"13","author":"Jia","year":"2025","journal-title":"Food Sci. Nutr."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Cho, K.H., and Kang, S.O. (2025). The Gut Microbiota of Drosophila melanogaster: A Model for Host-Microbe Interactions in Metabolism, Immunity, Behavior, and Disease. Microorganisms, 13.","DOI":"10.3390\/microorganisms13112515"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1126\/science.1212782","article-title":"Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling","volume":"334","author":"Shin","year":"2011","journal-title":"Science"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Wang, D., Zhang, Y., Xu, M., Sun, X., Cui, X., Wang, X., and Liu, D. (2022). Dietary Bacillus licheniformis improves the effect of Astragalus membranaceus extract on blood glucose by regulating antioxidation activity and intestinal microbiota in InR[E19]\/TM2 Drosophila melanogaster. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0271177"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Liang, H., Tao, S., Wang, Y., Zhao, J., Yan, C., Wu, Y., Liu, N., and Qin, Y. (2024). Astragalus polysaccharide: Implication for intestinal barrier, anti-inflammation, and animal production. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1364739"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Wang, B., Yan, L., Guo, S., Wen, L., Yu, M., Feng, L., and Jia, X. (2022). Structural Elucidation, Modification, and Structure-Activity Relationship of Polysaccharides in Chinese Herbs: A Review. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.908175"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Wang, L., Gao, M., Kang, G., and Huang, H. (2021). The Potential Role of Phytonutrients Flavonoids Influencing Gut Microbiota in the Prophylaxis and Treatment of Inflammatory Bowel Disease. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.798038"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"100275","DOI":"10.5493\/wjem.v15.i1.100275","article-title":"Impact of curcumin on gut microbiome","volume":"15","author":"Balaji","year":"2025","journal-title":"World J. Exp. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"e1525","DOI":"10.1002\/wsbm.1525","article-title":"Tumor models in various Drosophila tissues","volume":"13","author":"Gong","year":"2021","journal-title":"WIREs Mech. Dis."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"e09957","DOI":"10.1016\/j.heliyon.2022.e09957","article-title":"What we have learnt from Drosophila model organism: The coordination between insulin signaling pathway and tumor cells","volume":"8","author":"Weina","year":"2022","journal-title":"Heliyon"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"165880","DOI":"10.1016\/j.bbadis.2020.165880","article-title":"Bibliometric analysis of personalized humanized mouse and Drosophila models for effective combinational therapy in cancer patients","volume":"1866","author":"Kamdem","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1158\/1535-7163.MCT-19-0168","article-title":"An EGFR-Induced Drosophila Lung Tumor Model Identifies Alternative Combination Treatments","volume":"18","author":"Bossen","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1242\/dev.118.2.401","article-title":"Targeted gene expression as a means of altering cell fates and generating dominant phenotypes","volume":"118","author":"Brand","year":"1993","journal-title":"Development"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nrc1671","article-title":"Using Drosophila melanogaster to map human cancer pathways","volume":"5","author":"Brumby","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"ref_171","first-page":"221","article-title":"Cell competition in development, homeostasis and cancer","volume":"24","author":"Vermeulen","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0166-2236(00)01791-4","article-title":"Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development","volume":"24","author":"Lee","year":"2001","journal-title":"Trends Neurosci."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0896-6273(00)80701-1","article-title":"Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis","volume":"22","author":"Lee","year":"1999","journal-title":"Neuron"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"5769","DOI":"10.1093\/emboj\/cdg548","article-title":"scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila","volume":"22","author":"Brumby","year":"2003","journal-title":"EMBO J."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1126\/science.1088474","article-title":"A genetic screen in Drosophila for metastatic behavior","volume":"302","author":"Pagliarini","year":"2003","journal-title":"Science"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s12672-025-04248-7","article-title":"Applications and challenges of Drosophila melanogaster as a laboratory model in human cancer research: A narrative review","volume":"17","author":"Abdullateef","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.tig.2021.11.006","article-title":"State-of-the-art CRISPR for in vivo and cell-based studies in Drosophila","volume":"38","author":"Zirin","year":"2021","journal-title":"Trends Genet."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"6498","DOI":"10.1038\/s41467-025-61692-3","article-title":"Higher resolution pooled genome-wide CRISPR knockout screening in Drosophila cells using integration and anti-CRISPR (IntAC)","volume":"16","author":"Viswanatha","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S1383-5718(99)00020-0","article-title":"The w\/w+ SMART assay of Drosophila melanogaster detects the genotoxic effects of reactive oxygen species inducing compounds","volume":"440","author":"Sierra","year":"1999","journal-title":"Mutat. Res.\/Genet. Toxicol. Environ. Mutagen."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/mutage\/geh020","article-title":"Genotoxicity of tamoxifen citrate and 4-nitroquinoline-1-oxide in the wing spot test of Drosophila melanogaster","volume":"19","year":"2004","journal-title":"Mutagenesis"},{"key":"ref_181","unstructured":"Soloneski, S., and Larramendy, M.L. (2020). The w\/w\u00a0+ Somatic Mutation and Recombination Test (SMART) of Drosophila melanogaster for Detecting Antigenotoxic Activity. Genotoxicity and Mutagenicity\u2014Mechanisms and Test Methods, IntechOpen."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Sakane, F., Hoshino, F., Ebina, M., Sakai, H., and Takahashi, D. (2021). The Roles of Diacylglycerol Kinase \u03b1 in Cancer Cell Proliferation and Apoptosis. Cancers, 13.","DOI":"10.3390\/cancers13205190"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Sun, K., Jin, L., Karolov\u00e1, J., Vorwerk, J., Hailfinger, S., Opalka, B., Zapukhlyak, M., Lenz, G., and Khandanpour, C. (2023). Combination Treatment Targeting mTOR and MAPK Pathways Has Synergistic Activity in Multiple Myeloma. Cancers, 15.","DOI":"10.3390\/cancers15082373"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"207","DOI":"10.21037\/tcr-2025-aw-2397","article-title":"Vitamin B3 suppresses RasV12 -driven tumor growth in Drosophila via redox regulation, mitochondrial function, and autophagy activation","volume":"15","author":"Shen","year":"2026","journal-title":"Transl. Cancer Res."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"826","DOI":"10.21873\/invivo.14240","article-title":"Physalin A Suppresses Human Oral Squamous Carcinoma Cell Migration and Invasion Through Inhibiting Grb2\/Ras and MMP\/uPA Signaling Pathways","volume":"40","author":"Ma","year":"2026","journal-title":"In Vivo"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"108741","DOI":"10.1016\/j.bioorg.2025.108741","article-title":"Anti-metastatic cancer potential of 4H-chromene derivatives targeting JNK in Scribble knockdown induced epithelial cancer model: In vivo and in silico studies","volume":"163","author":"Raghuvanshi","year":"2025","journal-title":"Bioorg. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0092-8674(03)00557-9","article-title":"The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis","volume":"114","author":"Harvey","year":"2003","journal-title":"Cell"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S0092-8674(03)00549-X","article-title":"hippo Encodes a Ste-20 Family Protein Kinase that Restricts Cell Proliferation and Promotes Apoptosis in Conjunction with salvador and warts","volume":"114","author":"Wu","year":"2003","journal-title":"Cell"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/s41573-020-0070-z","article-title":"Targeting the Hippo pathway in cancer, fibrosis, wound healing and regenerative medicine","volume":"19","author":"Dey","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"22072","DOI":"10.1021\/acsomega.5c13279","article-title":"The Anticarcinogenicity Effects of Piperine and 4,5-Dihydroxypiperine in Drosophila melanogaster Somatic Cells","volume":"11","author":"Aguiar","year":"2026","journal-title":"ACS Omega"},{"key":"ref_191","first-page":"4663","article-title":"Screening of effective components of Psoralea Fructus for endometrial cancer by affinity ultrafiltration chromatography-mass spectrometry","volume":"55","author":"Jiang","year":"2024","journal-title":"Chin. Tradit. Herbal. Drugs"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/nature11127","article-title":"Chemical genetic discovery of targets and anti-targets for cancer polypharmacology","volume":"486","author":"Dar","year":"2012","journal-title":"Nature"},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Jiang, H., Kimura, T., Hai, H., Yamamura, R., and Sonoshita, M. (2022). Drosophila as a toolkit to tackle cancer and its metabolism. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.982751"},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Lee, Y., Lee, S.-H., Choi, D., Nam, H.-S., Kim, K.D., Choi, M.H., Cho, M.-K., and Lee, Y.-J. (2025). Resveratrol Targets Glycolytic Enzymes HK II and PKM2 to Promote Concurrent Apoptotic and Necrotic Cell Death in Malignant Melanoma. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47121006"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"375","DOI":"10.14740\/wjon2586","article-title":"Mechanism of Action of Resveratrol Affecting the Biological Function of Breast Cancer Through the Glycolytic Pathway","volume":"16","author":"Gao","year":"2025","journal-title":"World J. Oncol."},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Wei, R., Hackman, R.M., Wang, Y., and Mackenzie, G.G. (2019). Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts. Cancers, 11.","DOI":"10.3390\/cancers11101496"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"5682","DOI":"10.1039\/C8FO01397G","article-title":"Suppressing glucose metabolism with epigallocatechin-3-gallate (EGCG) reduces breast cancer cell growth in preclinical models","volume":"9","author":"Wei","year":"2018","journal-title":"Food Funct."},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Jin, L., Gao, F., Li, P., Yu, C., and Xiao, G. (2026). Genetic dissection of signalling pathways that mediate iron-related tumor growth in a Drosophila model. PLoS Genet., 22.","DOI":"10.1371\/journal.pgen.1012017"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"e57695","DOI":"10.15252\/embr.202357695","article-title":"Convergent insulin and TGF-\u03b2 signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model","volume":"24","author":"Bakopoulos","year":"2023","journal-title":"EMBO Rep."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"e107336","DOI":"10.15252\/embj.2020107336","article-title":"Host autophagy mediates organ wasting and nutrient mobilization for tumor growth","volume":"40","author":"Khezri","year":"2021","journal-title":"EMBO J."},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Singaravelan, N., and Tollefsbol, T.O. (2025). Polyphenol-Based Prevention and Treatment of Cancer Through Epigenetic and Combinatorial Mechanisms. Nutrients, 17.","DOI":"10.3390\/nu17040616"},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Altomare, C., Macr\u00ec, R., Serra, M., Ussia, S., Ritorto, G., Maiuolo, J., Muscoli, C., Perri, E., and Mollace, V. (2025). The Potential of Nutraceutical Supplementation in Counteracting Cancer Development and Progression: A Pathophysiological Perspective. Nutrients, 17.","DOI":"10.3390\/nu17142354"},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Elovsson, G., Bergkvist, L., and Brorsson, A.-C. (2021). Exploring A\u03b2 Proteotoxicity and Therapeutic Candidates Using Drosophila melanogaster. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910448"},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"Elovsson, G., Klingstedt, T., Brown, M., Nilsson, K.P.R., and Brorsson, A.-C. (2024). A Novel Drosophila Model of Alzheimer\u2019s Disease to Study A\u03b2 Proteotoxicity in the Digestive Tract. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042105"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/ahg.12554","article-title":"Using Drosophila amyloid toxicity models to study Alzheimer\u2019s disease","volume":"88","author":"Tsintzas","year":"2024","journal-title":"Ann. Hum. Genet."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"7788","DOI":"10.1002\/alz.14246","article-title":"A novel peptide-based tau aggregation inhibitor as a potential therapeutic for Alzheimer\u2019s disease and other tauopathies","volume":"20","author":"Aggidis","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/acschemneuro.2c00357","article-title":"Discovery of Dual A\u03b2\/Tau Inhibitors and Evaluation of Their Therapeutic Effect on a Drosophila Model of Alzheimer\u2019s Disease","volume":"13","author":"Gandini","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"4753","DOI":"10.1111\/febs.70140","article-title":"In vivo and in silico models of Drosophila for Parkinson\u2019s disease","volume":"292","author":"Cesur","year":"2025","journal-title":"FEBS J."},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Skoulakis, E.M.C., Carvajal-Oliveros, A., Dominguez-Bale\u00f3n, C., S\u00e1nchez-D\u00edaz, I., Zambrano-Tipan, D., Hern\u00e1ndez-Vargas, R., Campusano, J.M., Narv\u00e1ez-Padilla, V., and Reynaud, E. (2023). Parkinsonian phenotypes induced by Synphilin-1 expression are differentially contributed by serotonergic and dopaminergic circuits and suppressed by nicotine treatment. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0282348"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/s41422-019-0153-8","article-title":"Vitamin B12 modulates Parkinson\u2019s disease LRRK2 kinase activity through allosteric regulation and confers neuroprotection","volume":"29","author":"Schaffner","year":"2019","journal-title":"Cell Res."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.neures.2020.01.016","article-title":"PINK1-Parkin signaling in Parkinson\u2019s disease: Lessons from Drosophila","volume":"159","author":"Imai","year":"2020","journal-title":"Neurosci. Res."},{"key":"ref_212","first-page":"58","article-title":"Mitochondrial dynamics and mitophagy in Parkinson\u2019s disease: A fly point of view","volume":"90","author":"Nardin","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Yang, J., Kim, M.J., Yoon, W., Kim, E.Y., Kim, H., Lee, Y., Min, B., Kang, K.S., Son, J.H., and Park, H.T. (2017). Isocitrate protects DJ-1 null dopaminergic cells from oxidative stress through NADP+-dependent isocitrate dehydrogenase (IDH). PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006975"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1080\/1028415X.2025.2531356","article-title":"Targeting protein kinases in Parkinson\u2019s disease: The emerging role of phytoconstituents","volume":"28","author":"Joshi","year":"2025","journal-title":"Nutr. Neurosci."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1139\/bcb-2024-0280","article-title":"Targeting PINK1 using phytochemicals: Exploring molecular insights into Parkinson\u2019s disease therapeutics","volume":"103","author":"Nallusamy","year":"2025","journal-title":"Biochem. Cell Biol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/jez.70042","article-title":"Antioxidants and Parkinson\u2019s Disease: A Systematic Review and Meta-Analysis of Research Evidence and Prospectives Using the Drosophila Model","volume":"345","author":"Fathy","year":"2025","journal-title":"J. Exp. Zool. A Ecol. Integr. Physiol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"137187","DOI":"10.1016\/j.neulet.2023.137187","article-title":"Impact of age on the rotenone-induced sporadic Parkinson\u2019s disease model using Drosophila melanogaster","volume":"805","author":"Li","year":"2023","journal-title":"Neurosci. Lett."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"102004","DOI":"10.1016\/j.toxrep.2025.102004","article-title":"Ameliorative role of naringenin in MPTP- induced Parkinsonism: Insights from Drosophila melanogaster experimental model combined with computational biology","volume":"14","author":"Okonta","year":"2025","journal-title":"Toxicol. Rep."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"115002","DOI":"10.1016\/j.fct.2024.115002","article-title":"p-Coumaric acid potential in restoring neuromotor function and oxidative balance through the Parkin pathway in a Parkinson disease-like model in Drosophila melanogaster","volume":"193","author":"Poleto","year":"2024","journal-title":"Food Chem. Toxicol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1111\/ggi.14296","article-title":"Ethyl caffeate ameliorated amyloid-beta42 protein-associated toxicity in PC12 cells and Drosophila melanogaster","volume":"21","author":"Tan","year":"2021","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"587","DOI":"10.2174\/0115672050385870250721072643","article-title":"Neuroprotective Effects of Fenugreek Leaf Extract in a Drosophila Model of Alzheimer\u2019s Disease Expressing Human A\u03b2-42","volume":"22","author":"Varshney","year":"2025","journal-title":"Curr. Alzheimer Res."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"67716","DOI":"10.18632\/oncotarget.11963","article-title":"Quercetin ameliorates A\u03b2 toxicity in Drosophila AD model by modulating cell cycle-related protein expression","volume":"7","author":"Kong","year":"2016","journal-title":"Oncotarget"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"34784","DOI":"10.1038\/srep34784","article-title":"Attenuation of synaptic toxicity and MARK4\/PAR1-mediated Tau phosphorylation by methylene blue for Alzheimer\u2019s disease treatment","volume":"6","author":"Sun","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.neuro.2022.02.011","article-title":"Jatamansinol from Nardostachys jatamansi (D.Don) DC. Protects A\u03b242-Induced Neurotoxicity in Alzheimer\u2019s Disease Drosophila Model","volume":"90","author":"Anupama","year":"2022","journal-title":"Neurotoxicology"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"e00721","DOI":"10.1016\/j.neurot.2025.e00721","article-title":"Gaultheria leucocarpa inhibits A\u03b2 fibrillization and enhances mitophagy-mediated degradation of pathogenic proteins","volume":"22","author":"Zhang","year":"2025","journal-title":"Neurotherapeutics"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/s11011-025-01625-7","article-title":"Salvianolic acid B ameliorates A\u03b242 toxicity in A\u03b242-expressing Drosophila model: Behavioral and transcriptomic profiling","volume":"40","author":"Tan","year":"2025","journal-title":"Metab. Brain Dis."},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Ucar Akyurek, T., Senol Deniz, F.S., Erdogan Orhan, I., Gozuboyuk, M., Erdemli, G.I., and Emecen, G. (2026). Gallic Acid, 3-Hydroxytyrosol, and Quercetin Modulate Cholinesterase Activity in Drosophila melanogaster. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020859"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1097\/WNR.0000000000001599","article-title":"Vitamin K2 protects against A\u03b242-induced neurotoxicity by activating autophagy and improving mitochondrial function in Drosophila","volume":"32","author":"Lin","year":"2021","journal-title":"NeuroReport"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s11130-022-01016-8","article-title":"Neuroprotective Effects of Lycium Barbarum Fruit Extract on Pink1B9 Drosophila melanogaster Genetic Model of Parkinson\u2019s Disease","volume":"78","author":"Bai","year":"2022","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"112213","DOI":"10.1016\/j.jep.2019.112213","article-title":"Ginseng protein protects against mitochondrial dysfunction and neurodegeneration by inducing mitochondrial unfolded protein response in Drosophila melanogaster PINK1 model of Parkinson\u2019s disease","volume":"247","author":"Liu","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_231","first-page":"1","article-title":"Caffeine improves mitochondrial function in PINK1B9-null mutant Drosophila melanogaster","volume":"55","author":"Senger","year":"2022","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.exger.2018.09.014","article-title":"Grape skin extract improves muscle function and extends lifespan of a Drosophila model of Parkinson\u2019s disease through activation of mitophagy","volume":"113","author":"Wu","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_233","doi-asserted-by":"crossref","unstructured":"Chaouhan, H.S., Li, X., Sun, K.-T., Wang, I.K., Yu, T.-M., Yu, S.-H., Chen, K.-B., Lin, W.-Y., and Li, C.-Y. (2022). Calycosin Alleviates Paraquat-Induced Neurodegeneration by Improving Mitochondrial Functions and Regulating Autophagy in a Drosophila Model of Parkinson\u2019s Disease. Antioxidants, 11.","DOI":"10.3390\/antiox11020222"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/ame2.70106","article-title":"Polyphenol diet and exercise as neuroprotective factors in a Drosophila model of Alzheimer\u2019s disease","volume":"9","author":"Hartman","year":"2026","journal-title":"Anim. Models Exp. Med."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"3922","DOI":"10.1038\/s41598-022-07909-7","article-title":"An assessment of the rescue action of resveratrol in parkin loss of function-induced oxidative stress in Drosophila melanogaster","volume":"12","author":"Adedara","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"145811","DOI":"10.1016\/j.gene.2021.145811","article-title":"Saffron ameliorated motor symptoms, short life span and retinal degeneration in Parkinson\u2019s disease fly models","volume":"799","author":"Inoue","year":"2021","journal-title":"Gene"},{"key":"ref_237","first-page":"43","article-title":"Therapeutic potential of hesperidin in Parkinson\u2019s disease with dementia: Inhibition of alpha synuclein and amyloid beta in Drosophila melanogaster","volume":"36","author":"Ishola","year":"2021","journal-title":"Niger. J. Physiol. Sci."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"20190136","DOI":"10.1515\/jcim-2019-0136","article-title":"Synergistic action of propolis with levodopa in the management of Parkinsonism in Drosophila melanogaster","volume":"17","author":"Ayikobua","year":"2020","journal-title":"J. Complement. Integr. Med."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"e23332","DOI":"10.1002\/jbt.23332","article-title":"Ellagic acid mitigates rotenone-induced damage via modulating mitochondria function in Drosophila melanogaster","volume":"37","author":"Adedara","year":"2023","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_240","doi-asserted-by":"crossref","unstructured":"Ortega-Regules, A.E., Mart\u00ednez-Thomas, J.A., Sch\u00fcrenk\u00e4mper-Carrillo, K., de Parrodi, C.A., L\u00f3pez-Mena, E.R., Mej\u00eda-M\u00e9ndez, J.L., and Lozada-Ram\u00edrez, J.D. (2024). Recent Advances in the Therapeutic Potential of Carotenoids in Preventing and Managing Metabolic Disorders. Plants, 13.","DOI":"10.3390\/plants13121584"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"109615","DOI":"10.1016\/j.cbpc.2023.109615","article-title":"\u03b2-carotene-loaded nanoparticles protect against neuromotor damage, oxidative stress, and dopamine deficits in a model of Parkinson\u2019s disease in Drosophila melanogaster","volume":"268","author":"Chaves","year":"2023","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.fct.2010.10.029","article-title":"Astaxanthin protects against MPTP\/MPP+-induced mitochondrial dysfunction and ROS production in vivo and in vitro","volume":"49","author":"Lee","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_243","doi-asserted-by":"crossref","unstructured":"Luo, S., Zhang, L., Wu, X., Wang, J., Li, Q., Chen, W., Li, R., Zhou, L., Zhou, N., and Chen, R. (2026). Therapeutic potential of neuroprotective plant extracts in Parkinson\u2019s disease. Front. Neurosci., 20.","DOI":"10.3389\/fnins.2026.1813133"},{"key":"ref_244","doi-asserted-by":"crossref","unstructured":"Cord, D., R\u00eembu, M.C., Iordache, M.P., Albulescu, R., Pop, S., Tanase, C., and Popa, M.-L. (2025). Phytochemicals as Epigenetic Modulators in Chronic Diseases: Molecular Mechanisms. Molecules, 30.","DOI":"10.20944\/preprints202510.0134.v1"},{"key":"ref_245","doi-asserted-by":"crossref","unstructured":"Agrawal, P., Chung, P., Heberlein, U., and Kent, C. (2019). Enabling cell-type-specific behavioral epigenetics in Drosophila: A modified high-yield INTACT method reveals the impact of social environment on the epigenetic landscape in dopaminergic neurons. BMC Biol., 17.","DOI":"10.1186\/s12915-019-0646-4"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s10522-017-9700-1","article-title":"Hormetic efficacy of rutin to promote longevity in Drosophila melanogaster","volume":"18","author":"Chattopadhyay","year":"2017","journal-title":"Biogerontology"},{"key":"ref_247","doi-asserted-by":"crossref","unstructured":"De Lazzari, F., Sandrelli, F., Whitworth, A.J., and Bisaglia, M. (2020). Antioxidant Therapy in Parkinson\u2019s Disease: Insights from Drosophila melanogaster. Antioxidants, 9.","DOI":"10.3390\/antiox9010052"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"4120458","DOI":"10.1155\/2018\/4120458","article-title":"Recent Advances in Studies on the Therapeutic Potential of Dietary Carotenoids in Neurodegenerative Diseases","volume":"2018","author":"Cho","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1080\/17460441.2019.1569624","article-title":"An assessment of the translational relevance of Drosophila in drug discovery","volume":"14","author":"Papanikolopoulou","year":"2019","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_250","unstructured":"Gilbert, L.I. (2012). 8\u2014Insect CYP Genes and P450 Enzymes. Insect Molecular Biology and Biochemistry, Academic Press."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0378-1119(00)00533-3","article-title":"The cytochrome P450 gene superfamily in Drosophila melanogaster: Annotation, intron-exon organization and phylogeny","volume":"262","author":"Tijet","year":"2001","journal-title":"Gene"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1021\/tx700079z","article-title":"Cytochrome P450 and Chemical Toxicology","volume":"21","author":"Guengerich","year":"2007","journal-title":"Chem. Res. Toxicol."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.pharmthera.2012.12.007","article-title":"Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation","volume":"138","author":"Zanger","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1002\/j.1460-2075.1991.tb08047.x","article-title":"Mammalian genes expressed in Drosophila: A transgenic model for the study of mechanisms of chemical mutagenesis and metabolism","volume":"10","author":"Jowett","year":"1991","journal-title":"EMBO J."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.ibmb.2013.02.003","article-title":"Soluble and membrane-bound Drosophila melanogaster CYP6G1 expressed in Escherichia coli: Purification, activity, and binding properties toward multiple pesticides","volume":"43","author":"Cheesman","year":"2013","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cmet.2006.06.006","article-title":"The DHR96 nuclear receptor regulates xenobiotic responses in Drosophila","volume":"4","author":"Horner","year":"2006","journal-title":"Cell Metab."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1534\/genetics.106.066597","article-title":"Cis-regulatory elements in the Accord retrotransposon result in tissue-specific expression of the Drosophila melanogaster insecticide resistance gene Cyp6g1","volume":"175","author":"Chung","year":"2007","journal-title":"Genetics"},{"key":"ref_258","doi-asserted-by":"crossref","unstructured":"Hindle, S.J., and Bainton, R.J. (2014). Barrier mechanisms in the Drosophila blood-brain barrier. Front. Neurosci., 8.","DOI":"10.3389\/fnins.2014.00414"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1523\/JNEUROSCI.4367-07.2008","article-title":"Organization and function of the blood-brain barrier in Drosophila","volume":"28","author":"Stork","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_260","doi-asserted-by":"crossref","unstructured":"Limmer, S., Weiler, A., Volkenhoff, A., Babatz, F., and Kl\u00e4mbt, C. (2014). The Drosophila blood-brain barrier: Development and function of a glial endothelium. Front. Neurosci., 8.","DOI":"10.3389\/fnins.2014.00365"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/glia.21147","article-title":"Physiologic and anatomic characterization of the brain surface glia barrier of Drosophila","volume":"59","author":"DeSalvo","year":"2011","journal-title":"Glia"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/17\/1447\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:28:57Z","timestamp":1787560137000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/17\/1447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":261,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["biology15171447"],"URL":"https:\/\/doi.org\/10.3390\/biology15171447","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]}}}