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Xanthone <jats:bold>2a<\/jats:bold> was identified as the most active inhibitor against both \u03b1\u2010glucosidase and aldose reductase (ALR2), with IC<jats:sub>50<\/jats:sub> values of 7.8\u2009\u00b1\u20090.5\u2009\u03bcM and 63.2\u2009\u00b1\u20090.6\u2009nM, respectively, which was far active than acarbose (35.0\u2009\u00b1\u20090.1\u2009\u03bcM), and a little more active than epalrestat (67.0\u2009\u00b1\u20093.0\u2009nM). <jats:bold>2a<\/jats:bold> was also confirmed as the most active antioxidant in vitro with EC<jats:sub>50<\/jats:sub> value of 8.9\u2009\u00b1\u20090.1\u2009\u03bcM. Any structural modification including methylation, deletion, and position change of hydroxyl group in <jats:bold>2a<\/jats:bold> will cause an activity loss in inhibitory and antioxidation. By applying a H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced oxidative stress nematode model, it was confirmed that xanthone <jats:bold>2a<\/jats:bold> can be absorbed by <jats:italic>Caenorhabditis elegans<\/jats:italic> and is bioavailable to attenuate in vivo oxidative stress, including the effects on lifespan, superoxide dismutase, Catalase, and malondialdehyde. <jats:bold>2a<\/jats:bold> was verified with in vivo hypoglycemic effect and mitigation of embryo malformations in high glucose. All our data support that xanthone <jats:bold>2a<\/jats:bold> behaves triple roles and is a potential agent to treat diabetic mellitus, gestational diabetes mellitus, and diabetic complications.<\/jats:p>","DOI":"10.1002\/ddr.22170","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T01:12:10Z","timestamp":1710378730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Xanthones with multiple roles against diabetes: their synthesis, structure\u2010activity relationship, and mechanism studies"],"prefix":"10.1002","volume":"85","author":[{"given":"Youhong","family":"Ke","sequence":"first","affiliation":[{"name":"Institute of Traditional Chinese Medicine and Natural Products; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, College of Pharmacy Jinan University Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinfang","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Traditional Chinese Medicine and Natural Products; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, College of Pharmacy Jinan University Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianling","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Traditional Chinese Medicine and Natural Products; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, College of Pharmacy Jinan University Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianrun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Traditional Chinese Medicine and Natural Products; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, College of Pharmacy Jinan University Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijian","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Traditional Chinese Medicine and Natural Products; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, College of Pharmacy Jinan University Guangzhou People's Republic of China"},{"name":"Guangzhou PharmCherub Medicinal Sci. &amp; Tech. 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