{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T16:16:58Z","timestamp":1780417018486,"version":"3.54.1"},"reference-count":46,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Program of Belt and Road Innovative Talents Exchange of the Chinese Ministry of Science and Technology","award":["DL2023173001L"],"award-info":[{"award-number":["DL2023173001L"]}]},{"name":"National Program of Belt and Road Innovative Talents Exchange of the Chinese Ministry of Science and Technology","award":["S2024-YF-ZDCXL-ZDLSF-0183\/Se-2023C04\/2022ZDLSF05-11"],"award-info":[{"award-number":["S2024-YF-ZDCXL-ZDLSF-0183\/Se-2023C04\/2022ZDLSF05-11"]}]},{"name":"National Program of Belt and Road Innovative Talents Exchange of the Chinese Ministry of Science and Technology","award":["202305AF150118"],"award-info":[{"award-number":["202305AF150118"]}]},{"name":"Key Research and Development Program of Shaanxi Province and Ankang City (Key Laboratory of Se-enriched Products Development and Quality Control of Ministry of Agriculture and Rural Affairs and National-Local Joint Engineering Laboratory of Se-enriched Food Development)","award":["DL2023173001L"],"award-info":[{"award-number":["DL2023173001L"]}]},{"name":"Key Research and Development Program of Shaanxi Province and Ankang City (Key Laboratory of Se-enriched Products Development and Quality Control of Ministry of Agriculture and Rural Affairs and National-Local Joint Engineering Laboratory of Se-enriched Food Development)","award":["S2024-YF-ZDCXL-ZDLSF-0183\/Se-2023C04\/2022ZDLSF05-11"],"award-info":[{"award-number":["S2024-YF-ZDCXL-ZDLSF-0183\/Se-2023C04\/2022ZDLSF05-11"]}]},{"name":"Key Research and Development Program of Shaanxi Province and Ankang City (Key Laboratory of Se-enriched Products Development and Quality Control of Ministry of Agriculture and Rural Affairs and National-Local Joint Engineering Laboratory of Se-enriched Food Development)","award":["202305AF150118"],"award-info":[{"award-number":["202305AF150118"]}]},{"name":"Program of Academician and Expert Workstation in Puer City of Yunnan Province in China","award":["DL2023173001L"],"award-info":[{"award-number":["DL2023173001L"]}]},{"name":"Program of Academician and Expert Workstation in Puer City of Yunnan Province in China","award":["S2024-YF-ZDCXL-ZDLSF-0183\/Se-2023C04\/2022ZDLSF05-11"],"award-info":[{"award-number":["S2024-YF-ZDCXL-ZDLSF-0183\/Se-2023C04\/2022ZDLSF05-11"]}]},{"name":"Program of Academician and Expert Workstation in Puer City of Yunnan Province in China","award":["202305AF150118"],"award-info":[{"award-number":["202305AF150118"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) has become a worldwide public health problem. Epimedin C is considered one of the most important flavonoids in Epimedium, a famous edible herb in China and Southeast Asia that is traditionally used in herbal medicine to treat diabetes. In the present study, the therapeutic potential of epimedin C against T2DM was ascertained using a mouse model, and the mechanism underlying the hypoglycemic activity of epimedin C was explored using a label-free proteomic technique for the first time. Levels of fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance, as well as contents of malondialdehyde (MDA) and low-density lipoprotein cholesterol (LDL-C) in the 30 mg\u00b7kg\u22121 epimedin C group (EC30 group), were significantly lower than those in the model control group (MC group) (p &lt; 0.05), while the contents of hepatic glycogen, insulin, and high-density lipoprotein cholesterol (HDL-C), as well as activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the EC30 group were notably higher than those in the MC group (p &lt; 0.05). The structures of liver cells and tissues were greatly destroyed in the MC group, whereas the structures of cells and tissues were basically complete in the EC30 group, which were similar to those in the normal control group (NC group). A total of 92 differentially expressed proteins (DEPs) were enriched in the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In the EC30 vs. MC groups, the expression level of cytosolic phosphoenolpyruvate carboxykinase (Pck1) was down-regulated, while the expression levels of group XIIB secretory phospholipase A2-like protein (Pla2g12b), apolipoprotein B-100 (Apob), and cytochrome P450 4A14 (Cyp4a14) were up-regulated. According to the KEGG pathway assay, Pck1 participated in the gluconeogenesis and insulin signaling pathways, and Pla2g12b, Apob, and Cyp4a14 were the key proteins in the fat digestion and fatty acid degradation pathways. Pck1, Pla2g12b, Apob, and Cyp4a14 seemed to play important roles in the prevention and treatment of T2DM. In summary, epimedin C inhibited Pck1 expression to maintain FBG at a relatively stable level, promoted Pla2g12b, Apob, and Cyp4a14 expressions to alleviate liver lipotoxicity, and protected liver tissues and cells from oxidant stress possibly by its phenolic hydroxyl groups.<\/jats:p>","DOI":"10.3390\/nu16010025","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T03:36:17Z","timestamp":1703129777000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Mechanism Underlying the Hypoglycemic Effect of Epimedin C on Mice with Type 2 Diabetes Mellitus Based on Proteomic Analysis"],"prefix":"10.3390","volume":"16","author":[{"given":"Xuexue","family":"Zhou","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Academician and Expert Workstations in Puer City of Yunnan Province, College of Food Engineering and Nutritional Science, Provincial Research Station of Se-Enriched Foods in Hanyin County of Shaanxi Province, International Joint Research Center of Shaanxi Province for Food and Health Sciences, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Academician and Expert Workstations in Puer City of Yunnan Province, College of Food Engineering and Nutritional Science, Provincial Research Station of Se-Enriched Foods in Hanyin County of Shaanxi Province, International Joint Research Center of Shaanxi Province for Food and Health Sciences, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Yang","sequence":"additional","affiliation":[{"name":"Research Station of Selenium-Enriched Tea of Shaanxi Province, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Feng","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Academician and Expert Workstations in Puer City of Yunnan Province, College of Food Engineering and Nutritional Science, Provincial Research Station of Se-Enriched Foods in Hanyin County of Shaanxi Province, International Joint Research Center of Shaanxi Province for Food and Health Sciences, Shaanxi Normal University, Xi\u2019an 710119, China"},{"name":"Agrarian and Technological Institute, Peoples\u2019 Friendship University of Russia, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-2696","authenticated-orcid":false,"given":"Murat Sabirovich","family":"Gins","sequence":"additional","affiliation":[{"name":"Agrarian and Technological Institute, Peoples\u2019 Friendship University of Russia, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyu","family":"Yan","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Academician and Expert Workstations in Puer City of Yunnan Province, College of Food Engineering and Nutritional Science, Provincial Research Station of Se-Enriched Foods in Hanyin County of Shaanxi Province, International Joint Research Center of Shaanxi Province for Food and Health Sciences, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Han","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Academician and Expert Workstations in Puer City of Yunnan Province, College of Food Engineering and Nutritional Science, Provincial Research Station of Se-Enriched Foods in Hanyin County of Shaanxi Province, International Joint Research Center of Shaanxi Province for Food and Health Sciences, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5745-1783","authenticated-orcid":false,"given":"Huafeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Academician and Expert Workstations in Puer City of Yunnan Province, College of Food Engineering and Nutritional Science, Provincial Research Station of Se-Enriched Foods in Hanyin County of Shaanxi Province, International Joint Research Center of Shaanxi Province for Food and Health Sciences, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"ref_1","unstructured":"Magliano, D.J., Boyko, E.J., and IDF Diabetes Atlas 10th Edition Scientific Committee (2022, September 23). 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