{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:18:22Z","timestamp":1783055902269,"version":"3.54.6"},"reference-count":31,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005891","name":"State Administration of Traditional Chinese Medicine","doi-asserted-by":"crossref","award":["zyyzdxk-2023186"],"award-info":[{"award-number":["zyyzdxk-2023186"]}],"id":[{"id":"10.13039\/501100005891","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Guizhou University of Traditional Chinese Medicine","award":["([2025] No. 16)"],"award-info":[{"award-number":["([2025] No. 16)"]}]},{"DOI":"10.13039\/501100004731","name":"Zhejiang Provincial Natural Science Foundation for Young Scientists","doi-asserted-by":"publisher","award":["LQN25H280004"],"award-info":[{"award-number":["LQN25H280004"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The treatment of type 2 diabetes (T2DM) faces numerous challenges. Oral insulin (Ins) and other short-acting compounds still encounter significant obstacles in the hostile gastrointestinal environment, including low bioavailability and rapid metabolic clearance. Platycodin D (PD) is a natural compound with demonstrated hypoglycemic and lipid-lowering effects. In this study, PD was encapsulated using alginate to prepare orally administrable, pH-responsive, gut-targeted gel microspheres (PD@MPs), and their efficacy in improving T2DM prognosis was investigated. In vitro release studies demonstrated that PD@MPs avoided degradation by gastric acid and were released in the intestine. Cell experiments indicated that PD possessed significant antioxidant and anti-apoptotic properties. Masson, immunohistochemistry, and immunofluorescence staining revealed that PD@MPs alleviated inflammation in key metabolic organs and maintained normal pancreatic tissue function and morphology. Western blot analysis assessed the expression of proteins related to hepatic glycogen synthesis, including IRS-1, GLUT2, GSK-3\u03b2, and AKT. The research results indicate that the assembly strategy using sodium alginate (SA) as the coating layer has enabled the oral administration of PD and has demonstrated its potential in the treatment of diabetes.<\/jats:p>","DOI":"10.3390\/molecules31132305","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:41:38Z","timestamp":1782909698000},"page":"2305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preparation of Platycodin D Microspheres and Their Protective Effects on Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"31","author":[{"given":"Jingjing","family":"Huang","sequence":"first","affiliation":[{"name":"Pharmacy College, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"Blumea Balsamifera Research Center, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"Guizhou Research Center of Conservation and Utilization of Wild Resources of Karst Traditional Chinese Medicine and Ethnic Medicine, Anshun 561000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Han","sequence":"additional","affiliation":[{"name":"Pharmacy College, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"Blumea Balsamifera Research Center, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"Guizhou Research Center of Conservation and Utilization of Wild Resources of Karst Traditional Chinese Medicine and Ethnic Medicine, Anshun 561000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Yang","sequence":"additional","affiliation":[{"name":"Pharmacy College, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"Blumea Balsamifera Research Center, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"Guizhou Research Center of Conservation and Utilization of Wild Resources of Karst Traditional Chinese Medicine and Ethnic Medicine, Anshun 561000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Subtropical Silviculture, College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Pang","sequence":"additional","affiliation":[{"name":"Pharmacy College, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"Blumea Balsamifera Research Center, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"Guizhou Research Center of Conservation and Utilization of Wild Resources of Karst Traditional Chinese Medicine and Ethnic Medicine, Anshun 561000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfei","family":"Li","sequence":"additional","affiliation":[{"name":"Pharmacy College, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"Blumea Balsamifera Research Center, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"Guizhou Research Center of Conservation and Utilization of Wild Resources of Karst Traditional Chinese Medicine and Ethnic Medicine, Anshun 561000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12986-015-0057-7","article-title":"Antidiabetic properties of dietary flavonoids: A cellular mechanism review","volume":"12","author":"Vinayagam","year":"2015","journal-title":"Nutr. Metab."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12933-019-0900-7","article-title":"Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: A systematic review and an updated meta-analysis","volume":"18","author":"Han","year":"2019","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"load031","DOI":"10.1093\/lifemeta\/load031","article-title":"Glucokinase and glucokinase activator","volume":"2","author":"Li","year":"2023","journal-title":"Life Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1001\/jama.2018.18269","article-title":"Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial","volume":"321","author":"Rosenstock","year":"2019","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1038\/s12276-021-00624-9","article-title":"Platycodin D, a natural component of Platycodon grandiflorum, prevents both lysosome- and TMPRSS2-driven SARS-CoV-2 infection by hindering membrane fusion","volume":"53","author":"Kim","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1055\/s-0032-1315147","article-title":"Platycodin D inhibits lipogenesis through AMPK\u03b1-PPAR\u03b32 in 3T3-L1 cells and modulates fat accumulation in obese mice","volume":"78","author":"Lee","year":"2012","journal-title":"Planta Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12516","DOI":"10.1021\/acs.jafc.3c08490","article-title":"Platycodin D Ameliorates Cognitive Impairment in Type 2 Diabetes Mellitus Mice via Regulating PI3K\/Akt\/GSK3\u03b2 Signaling Pathway","volume":"72","author":"Lu","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1039\/D2FO03308A","article-title":"Platycodin D ameliorates hyperglycaemia and liver metabolic disturbance in HFD\/STZ-induced type 2 diabetic mice","volume":"14","author":"Shen","year":"2023","journal-title":"Food Funct."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.intimp.2004.04.005","article-title":"Platycodin D and D3 isolated from the root of Platycodon grandiflorum modulate the production of nitric oxide and secretion of TNF-alpha in activated RAW 264.7 cells","volume":"4","author":"Wang","year":"2004","journal-title":"Int. Immunopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1007\/s11064-020-03198-6","article-title":"Platycodin D Inhibits \u03b2-Amyloid-Induced Inflammation and Oxidative Stress in BV-2 Cells Via Suppressing TLR4\/NF-\u03baB Signaling Pathway and Activating Nrf2\/HO-1 Signaling Pathway","volume":"46","author":"Zhang","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.taap.2013.01.001","article-title":"Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and highglucose-exposed HepG2 cells","volume":"267","author":"YongPil","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S161","DOI":"10.1002\/ptr.3054","article-title":"Platycodin D inhibits adipogenesis of 3T3-L1 cells by modulating Kruppel-like factor 2 and peroxisome proliferator-activated receptor gamma","volume":"24","author":"Lee","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Miku\u0161ov\u00e1, V., and Miku\u0161, P. (2021). Advances in Chitosan-Based Nanoparticles for Drug Delivery. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179652"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.ijbiomac.2020.06.180","article-title":"Structures, properties and application of alginic acid: A review","volume":"162","author":"Guo","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E15701638372447","DOI":"10.2174\/0115701638372447250515104200","article-title":"Unlocking the Potential of Alginate Polymers: A Review of Recent Advances in Physicochemical Modulation for Versatile Biomaterials","volume":"23","author":"Mane","year":"2025","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"392001","DOI":"10.1088\/1361-6528\/ad5db5","article-title":"Nanomaterials for diabetes: Diagnosis, detection and delivery","volume":"35","author":"Verma","year":"2024","journal-title":"Nanotechnology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100739","DOI":"10.1016\/j.mtbio.2023.100739","article-title":"Zn(2+) incorporated composite polysaccharide microspheres for sustained growth factor release and wound healing","volume":"22","author":"Ju","year":"2023","journal-title":"Mater. Today Bio"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.ijbiomac.2022.03.207","article-title":"Effect of crosslinking strategy on the biological, antibacterial and physicochemical performance of hyaluronic acid and \u025b-polylysine based hydrogels","volume":"208","author":"Sceglovs","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.molmed.2017.03.004","article-title":"ROS in Cancer: The Burning Question","volume":"23","author":"Chio","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1111\/ggi.14979","article-title":"Individualized treatment of diabetes mellitus in older adults","volume":"24","author":"Araki","year":"2024","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.ijbiomac.2022.06.147","article-title":"Polysaccharide from Hovenia dulcis (Guaizao) improves pancreatic injury and regulates liver glycometabolism to alleviate STZ-induced type 1 diabetes mellitus in rats","volume":"214","author":"Yang","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Fang, X., Wei, J., Miao, R., Wu, H., Ma, K., and Tian, J. (2022). PDX-1: A Promising Therapeutic Target to Reverse Diabetes. Biomolecules, 12.","DOI":"10.3390\/biom12121785"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"22","DOI":"10.4103\/jcrt.JCRT_862_16","article-title":"Oxidative stress and its role in cancer","volume":"17","author":"Jelic","year":"2021","journal-title":"J. Cancer Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jep.2012.04.014","article-title":"Antidiabetic and antioxidant potential of Emblica officinalis Gaertn. leaves extract in streptozotocin-induced type-2 diabetes mellitus (T2DM) rats","volume":"142","author":"Nain","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"159234","DOI":"10.1016\/j.bbalip.2022.159234","article-title":"Empagliflozin ameliorates type 2 diabetes mellitus-related diabetic nephropathy via altering the gut microbiota","volume":"1867","author":"Deng","year":"2022","journal-title":"Biochim Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_27","first-page":"542","article-title":"Scutellarin alleviates liver injury in type 2 diabetic mellitus by suppressing hepatocyte apoptosis in vitro and in vivo","volume":"15","author":"Fan","year":"2023","journal-title":"Chin. Herb. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"120062","DOI":"10.1016\/j.lfs.2021.120062","article-title":"A new mouse model of type 2 diabetes mellitus established through combination of high-fat diet, streptozotocin and glucocorticoid","volume":"286","author":"Liu","year":"2021","journal-title":"Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s43556-022-00087-y","article-title":"C(- 106)T polymorphism in ALR2 and risk of microvascular complications in T2DM patients in north Indian population","volume":"3","author":"Mishra","year":"2022","journal-title":"Mol. BioMed"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"eabm4677","DOI":"10.1126\/sciadv.abm4677","article-title":"Efficient oral insulin delivery enabled by transferrin-coated acid-resistant metal-organic framework nanoparticles","volume":"8","author":"Zou","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1007\/s00125-016-3965-9","article-title":"Glucagon is the key factor in the development of diabetes","volume":"59","author":"Lee","year":"2016","journal-title":"Diabetologia"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/13\/2305\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:41:23Z","timestamp":1783053683000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/13\/2305"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":31,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["molecules31132305"],"URL":"https:\/\/doi.org\/10.3390\/molecules31132305","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]}}}