{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:20:26Z","timestamp":1791084026055,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFF1100204"],"award-info":[{"award-number":["2022YFF1100204"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Herbal formulas are unsuitable for routine dietary use. This study evaluates Qige Pipa Decoction (QPD), a food\u2013medicine homologous formula containing edible components, comparing its anti-diabetic effects with the classic Gegen Qinlian Decoction (GQD) to explore its potential as a sustainable dietary intervention for T2DM. Methods: T2DM mice received QPD, GQD, or metformin for 6 weeks. Parameters included glycemic control, histopathology, gut microbiota (16S rRNA), serum metabolomics, liver transcriptomics, and chemical profiling (UPLC-Q-TOF-MS). Results: Both formulas comparably improved glycemia and insulin resistance. QPD uniquely enriched beneficial gut bacteria (e.g., Roseburia) and suppressed pro-inflammatory taxa. Metabolomics revealed decreased Carnitine C20:1 and increased phospholipids in the QPD group. Transcriptomics showed QPD enriched the AGE-RAGE signaling pathway. Chemically, QPD showed relatively higher signal intensities for glycosides and organic acids, while GQD showed relatively higher signal intensities for alkaloids. Conclusions: QPD exhibits anti-diabetic efficacy similar to GQD but through distinct regulatory mechanisms. Its food-medicine homologous composition provides a theoretical rationale for its exploration as a sustained dietary adjunct. However, the absence of safety biomarkers in this study precludes definitive conclusions regarding long-term tolerability, necessitating dedicated toxicological assessment in future trials.<\/jats:p>","DOI":"10.3390\/ph19040530","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T12:05:49Z","timestamp":1775563549000},"page":"530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Beneficial Effects of Gegen Qinlian Decoction and Its Food\u2013Medicine Homologous Alternative Formulas Against Type 2 Diabetes Mellitus: Insights from Multi-Omics Analysis"],"prefix":"10.3390","volume":"19","author":[{"given":"Yao","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuming","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9259-1992","authenticated-orcid":false,"given":"Maomao","family":"Zeng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-1686","authenticated-orcid":false,"given":"Zhiyong","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1007\/s11427-024-3036-4","article-title":"Global risk factors, epidemiology, and disease burden of type 2 diabetes","volume":"69","author":"Chen","year":"2025","journal-title":"Sci. China Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Khalid, M., Alkaabi, J., Khan, M.A.B., and Adem, A. (2021). Insulin signal transduction perturbations in insulin resistance. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168590"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"130","DOI":"10.4239\/wjd.v14.i3.130","article-title":"Pancreatic \u03b2-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress","volume":"14","author":"Dludla","year":"2023","journal-title":"World J. Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"109090","DOI":"10.3748\/wjg.v31.i29.109090","article-title":"Gut-liver axis in diabetes: Mechanisms and therapeutic opportunities","volume":"31","author":"Abdalla","year":"2025","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Guo, H., Pan, L., Wu, Q., Wang, L., Huang, Z., Wang, J., Wang, L., Fang, X., Dong, S., and Zhu, Y. (2025). Type 2 diabetes and the multifaceted gut-X axes. Nutrients, 17.","DOI":"10.3390\/nu17162708"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1080\/10408398.2018.1536646","article-title":"Dietary compounds and traditional Chinese medicine ameliorate type 2 diabetes by modulating gut microbiota","volume":"59","author":"Nie","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Feng, Y., Ren, Y., Zhang, X., Yang, S., Jiao, Q., Li, Q., and Jiang, W. (2024). Metabolites of traditional Chinese medicine targeting PI3K\/AKT signaling pathway for hypoglycemic effect in type 2 diabetes. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1373711"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"113129","DOI":"10.1016\/j.jep.2020.113129","article-title":"Study on the mechanism of Gegen Qinlian Decoction for treating type II diabetes mellitus by integrating network pharmacology and pharmacological evaluation","volume":"262","author":"Xu","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"pbae003","DOI":"10.1093\/pcmedi\/pbae003","article-title":"Double-blinded, randomized clinical trial of Gegen Qinlian decoction pinpoints Faecalibacterium as key gut bacteria in alleviating hyperglycemia","volume":"7","author":"Gao","year":"2024","journal-title":"Precis. Clin. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"155329","DOI":"10.1016\/j.phymed.2023.155329","article-title":"Study on the mechanism of modified Gegen Qinlian decoction in regulating the intestinal flora-bile acid-TGR5 axis for the treatment of type 2 diabetes mellitus based on macro genome sequencing and targeted metabonomics integration","volume":"132","author":"Liu","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1142\/S0192415X25500648","article-title":"A comprehensive review on botany, ethnopharmacology, phytochemistry, biosynthesis, pharmacology, toxicity, quality control and metabolomics of coptidis rhizome","volume":"53","author":"Liao","year":"2025","journal-title":"Am. J. Chin. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"284","DOI":"10.4103\/2311-8571.392881","article-title":"A review on radix scutellariae: A traditional Chinese medicine with great medicinal significant","volume":"10","author":"Koriem","year":"2024","journal-title":"World J. Tradit. Chin. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1080\/13880209.2018.1492620","article-title":"A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis","volume":"56","author":"Wang","year":"2018","journal-title":"Pharm. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Liu, S., Wang, L., Zhang, Z., Leng, Y., Yang, Y., Fu, X., Xie, H., Gao, H., and Xie, C. (2024). The potential of astragalus polysaccharide for treating diabetes and its action mechanism. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1339406"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/13880209.2019.1577466","article-title":"Coptidis Rhizoma: A comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology","volume":"57","author":"Wang","year":"2019","journal-title":"Pharm. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8888528","DOI":"10.1155\/bmri\/8888528","article-title":"Investigating of the Phytoconstituents, Anti-\u03b1-Glucosidase, Antilipase, Anti-\u03b1-Amylase, and DPPH Radical Scavenging Activities of Extracts From Eriobotrya japonica","volume":"2025","author":"Jaradat","year":"2025","journal-title":"BioMed Res. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000152019","article-title":"Pathophysiology of Diabetes Mellitus type 2: Roles of obesity, insulin resistance and B-cell dysfunction","volume":"19","author":"Thevenod","year":"2008","journal-title":"Epidemiol. Evid. Mol. Links Front Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9827","DOI":"10.1038\/s41598-018-28029-1","article-title":"Mechanistic insights into the augmented effect of bone marrow mesenchymal stem cells and thiazolidinediones in streptozotocin-nicotinamide induced diabetic rats","volume":"8","author":"Hamza","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chong, S., Lin, M., Chong, D., Jensen, S., and Lau, N.S. (2025). A systematic review on gut microbiota in type 2 diabetes mellitus. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1486793"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Xu, Z., Zhou, Y., Xie, R., and Ning, Z. (2025). Metabolomics uncovers the diabetes metabolic network: From pathophysiological mechanisms to clinical applications. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1624878"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5190","DOI":"10.1038\/ncomms6190","article-title":"Integrated control of hepatic lipogenesis versus glucose production requires FoxO transcription factors","volume":"5","author":"Haeusler","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/aps.2016.165","article-title":"A new method to evaluate the dose-effect relationship of a TCM formula Gegen Qinlian Decoction:\u201cFocus\u201d mode of integrated biomarkers","volume":"38","author":"Huang","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.tibtech.2015.06.011","article-title":"Proteobacteria: Microbial signature of dysbiosis in gut microbiota","volume":"33","author":"Shin","year":"2015","journal-title":"Trends Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Jiang, X., Lu, N., Zhao, H., Yuan, H., Xia, D., and Lei, H. (2020). The microbiome\u2013metabolome response in the colon of piglets under the status of weaning stress. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.02055"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Liberty, I.A., Hanifah, L., Rachmat, H.F., Putri, A.A., Pratiwi, D., Pramono, A.P., Idris, F., and Tjekyan, S. (2025). Implication of taxonomic abundance of gut microbiota in prediabetes: A systematic review. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1577528"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1089\/ars.2021.0095","article-title":"Evidence for constitutive microbiota-dependent short-term control of food intake in mice: Is there a link with inflammation, oxidative stress, endotoxemia, and Glp-1?","volume":"37","author":"Salvi","year":"2022","journal-title":"Antioxid. Redox Signal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"829","DOI":"10.3390\/nu5030829","article-title":"The role of gut microbiota on insulin resistance","volume":"5","author":"Caricilli","year":"2013","journal-title":"Nutrients"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2337\/db12-0466","article-title":"Acylcarnitines: Reflecting or inflicting insulin resistance?","volume":"62","author":"Schooneman","year":"2013","journal-title":"Diabetes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2300416","DOI":"10.1002\/advs.202300416","article-title":"Hepatic phospholipid remodeling modulates insulin sensitivity and systemic metabolism","volume":"10","author":"Tian","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Qiao, X., Wang, Q., Wang, S., Kuang, Y., Li, K., Song, W., and Ye, M. (2018). A 42-markers pharmacokinetic study reveals interactions of berberine and glycyrrhizic acid in the anti-diabetic Chinese medicine formula Gegen-Qinlian decoction. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00622"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1136\/gut.25.7.756","article-title":"Classification of pancreatitis","volume":"25","author":"Sarner","year":"1984","journal-title":"Gut"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/4\/530\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T04:18:12Z","timestamp":1775621892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/4\/530"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ph19040530"],"URL":"https:\/\/doi.org\/10.3390\/ph19040530","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]}}}