{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:14:09Z","timestamp":1785420849125,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tianjin Natural Science Foundation Project","award":["23JCYBJC00850"],"award-info":[{"award-number":["23JCYBJC00850"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072709,81902441"],"award-info":[{"award-number":["82072709,81902441"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82072709,81902441"],"award-info":[{"award-number":["82072709,81902441"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type II diabetes mellitus (T2DM), a chronic metabolic disorder characterized by insulin resistance, is often accompanied by dysregulated bile acid metabolism. Although gastrodin, a bioactive compound derived from Gastrodia elata, has demonstrated potential in diabetes management, its therapeutic mechanisms remain incompletely understood. The aim of this study is to investigate the therapeutic effects and potential mechanisms of gastrodin on T2DM mice from the perspective of bile acid metabolism. In this study, we found that gastrodin could not only reduce lipid accumulation, reduce inflammation, improve antioxidant capacity, alleviate oxidative stress, change the composition of intestinal flora, and improve the disorder of flora caused by the disease in T2DM mice, but also target Yin yang 1 (YY1) to reduce the expression level of YY1 in the liver under a high-fat diet condition. At the same time, YY1 negatively regulates the expression level of Farnesoid X Receptor (FXR), which increases the expression level of FXR, inhibits the enzyme activity of Cholesterol-7\u03b1-hydroxylase (CYP7A1) through Small Heterodimer Partner (SHP), reduces the production of chenodeoxycholic acid (CDCA) in the liver, and further affects the production of secondary bile acids through liver\u2013intestinal circulation, promoting the secretion of Glucagon-Like Peptide-1 (GLP-1) and insulin, thereby reducing blood glucose. At the same time, combined with the results of HE staining, gastrodin can reduce the pathological damage of the liver and pancreas in type II diabetic mice, repairing their normal morphology and function. It provides a direct pathological basis for the improvement of diabetes and liver complications, provides theoretical support for the subsequent research and development of precision targeted drugs, provides experimental basis for the development of new natural hypoglycemic drugs, and promotes the transformation and application of the modernization of traditional Chinese medicine in the field of metabolic diseases.<\/jats:p>","DOI":"10.3390\/ijms27104593","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:12:54Z","timestamp":1779286374000},"page":"4593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gastrodin Ameliorates Type II Diabetes Through the YY1\u2013FXR\u2013Bile Acid Axis"],"prefix":"10.3390","volume":"27","author":[{"given":"Xiaolin","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, 300457 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushan","family":"Du","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, 300457 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penghui","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, 300457 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiji","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, 300457 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengya","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, 300457 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, 300457 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Du","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, 300457 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyao","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, 300457 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulu","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, 300457 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Sui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, 300457 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, 300457 Tianjin, China"},{"name":"Tianjin Agricultural University Nutritious and Healthy Food Sino-Thailand Joint Research Center, Tianjin Agricultural University, No. 22, Jinjing Road, 300380 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Meng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, No. 29, 13th Avenue, TEDA, 300457 Tianjin, China"},{"name":"Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Guangxi Medical University, No. 22, Shuangyong Road, 530021 Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.2337\/db09-9028","article-title":"From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus","volume":"58","author":"DeFronzo","year":"2009","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Singh, R., Gholipourmalekabadi, M., and Shafikhani, S.H. 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