{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:16:48Z","timestamp":1787015808537,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterised by absolute or relative insufficiency of insulin secretion. The alkaloids from\n                      <jats:italic>Rhizoma coptidis<\/jats:italic>\n                      have potential hypoglycemic effects. Epiberberine (EPI), a protoberberine alkaloid extracted from\n                      <jats:italic>Rhizome coptidis<\/jats:italic>\n                      , has been found to regulate lipid metabolism. Our study aimed to investigate the antidiabetic effects of EPI on mice with T2DM, as well as its underlying mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The T2DM model in mice was established using a combination of high\u2010fat diet and streptozotocin. Animals were divided into the control, T2DM, EPI\u2010low dose (50\u2009mg\/kg EPI), EPI\u2010medium dose (100\u2009mg\/kg EPI), EPI\u2010high dose (200\u2009mg\/kg EPI) and metformin (MTF) (200\u2009mg\/kg MTF) groups. Body weight, water\/food intake, serum lipids, blood glucose tolerance, insulin sensitivity, histopathological alterations, insulin signalling pathway and inflammation\u2010related pathways in each group were detected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EPI significantly reduced blood glucose levels and water\/food intake in T2DM mice. EPI reduced the levels of total cholesterol, total triglyceride, low\u2010density lipoprotein cholesterol, aspartate aminotransferase and alanine aminotransferase, and elevated the levels of high\u2010density lipoprotein cholesterol in serum. EPI effectively improved oral glucose tolerance, alleviated hepatic insulin resistance, decreased glycosylated haemoglobin levels and increased liver glycogen content. EPI ameliorated the histopathological alterations of skeletal muscle and liver in T2DM mice. EPI stimulated the insulin signalling pathway by increasing glucose transporter type 4 levels and activating insulin receptor substrate\u20101, phosphatidylinositol 3\u2010kinase and protein kinase B in skeletal muscle and liver. EPI reduced the levels of proinflammatory cytokine in serum and inhibited the activation of mitogen\u2010activated protein kinase signalling in skeletal muscle and liver of diabetic mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, these data demonstrate that EPI alleviates the symptoms of T2DM, providing new insights into EPI as a therapeutic compound for the alleviation of T2DM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nep.14430","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T18:42:06Z","timestamp":1738262526000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Epiberberine Improves Hyperglycemia and Ameliorates Insulin Sensitivity in Type 2 Diabetic Mice"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5591-4493","authenticated-orcid":false,"given":"Xiaohong","family":"Ma","sequence":"first","affiliation":[{"name":"Nephrology Department Shenzhen Bao'an Authentic Tcm Therapy Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Shi","sequence":"additional","affiliation":[{"name":"Internal Medicine Department Shenzhen Bao'an Authentic Tcm Therapy Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitao","family":"Shang","sequence":"additional","affiliation":[{"name":"Internal Medicine Department Shenzhen Bao'an Authentic Tcm Therapy Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2021.e07903"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154890"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2021.10.008"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155142"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-022-04587-x"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216179"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26896"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20221066"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399411002109"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.12.005"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-018-1337-3"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114713"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00805"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21302"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012064"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2020.104771"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.11.017"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.166639"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153488"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9FO00095J"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15700"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4530(02)00108-7"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-017-1839-4"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2021_574"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000022066"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000022032"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/2074610"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15092023"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/adar.2023.11812"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00508-023-02184-6"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/8278744"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13082550"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.117931"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106987"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00448-y"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1177\/03000605231164548"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22157797"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gie.2024.01.031"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.31128\/AJGP-03-21-5866"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450116666150727123115"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1066279"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.561956"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12236"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0939"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200601065"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1159\/000475912"},{"issue":"3","key":"e_1_2_12_48_1","first-page":"538","article-title":"Interleukin\u20101\u03b2 and C\u2010Reactive Protein Level in Plasma and Gingival Crevicular Fluid in Adolescents With Diabetes Mellitus","volume":"50","author":"Li X.","year":"2018","journal-title":"Beijing Da Xue Xue Bao. Yi Xue Ban"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.8.4171"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.12.9047"}],"container-title":["Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nep.14430","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T22:43:02Z","timestamp":1741128182000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nep.14430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,30]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/nep.14430"],"URL":"https:\/\/doi.org\/10.1111\/nep.14430","archive":["Portico"],"relation":{},"ISSN":["1320-5358","1440-1797"],"issn-type":[{"value":"1320-5358","type":"print"},{"value":"1440-1797","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,30]]},"assertion":[{"value":"2024-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14430"}}