{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:43:47Z","timestamp":1760060627402,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific and Technological Innovation Project of the China Academy of Chinese Medical Science","award":["CI2021A00104","KYG-202407","YZX-202247"],"award-info":[{"award-number":["CI2021A00104","KYG-202407","YZX-202247"]}]},{"name":"Institute of Basic Theory of Traditional Chinese Medicine Independent Research Project of Chinese Academy of Traditional Chinese Medicine","award":["CI2021A00104","KYG-202407","YZX-202247"],"award-info":[{"award-number":["CI2021A00104","KYG-202407","YZX-202247"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: The dysregulation of both glucose and lipid metabolism is the main clinical features of type 2 diabetes. Qihua Tongtiao Formula (QHTTF) is our team\u2019s current clinical empirical formula, and the related patent has been granted. It is composed of Astragalus membranaceus, Atractylodes macrocephala koidz, Aurantii Fructus Immaturus, Radix Bupleuri, Ligusticum chuanxiong hort, Angelicae sinensis radix, Raphanus sativus, and Polyporus umbellatus. It can alleviate tissue pathological damage in type 2 diabetic rats by improving glycolipid metabolism disorders. Nevertheless, the specific mechanisms of QHTTF in the treatment of type 2 diabetes remain unclear. Purpose: This research aims to explore the fundamental effect and underlying mechanism of the QHTTF formula in ZDF rats via network pharmacology, biological validation, and metabolomics technology. Methods: The chemical compounds of QHTTF were initially identified via UHPLC-MS\/MS analysis. Meanwhile, drug targets, genes, related diseases, and differential metabolites of QHTTF in the treatment of T2DM were obtained through network pharmacology, molecular docking, and metabolomics. Then, we conducted animal experiments to further explore the therapeutic molecular mechanism of QHTTF in ZDF rats. Results: A total of 39 main chemical components were recognized through LC-MS\/MS technology, and 22 remained after the second screening. Network pharmacology and molecular docking results revealed that 59 intersection targets were involved in the treatment of glycolipid metabolic disorders, and the PPAR\u03b1, PPAR\u03b3, and TNF proteins were identified as crucial targets through PPI network analysis. Additionally, serum metabolomics analysis of ZDF rats showed that QHTTF could regulate linoleic acid metabolism, fructose and mannose metabolism, galactose metabolism, fatty acid biosynthesis, and other related signaling pathways. The results of biological experiments proved that QHTTF effectively lowered blood glucose and lipid levels, alleviated hepatic and pancreatic pathological damage, increased the expression of IRS-1 and GLUT4 in the pancreas, and improved insulin resistance, while inhibiting the inflammatory response and oxidative stress, as well as enhancing the expression of liver PPAR\u03b1, PPAR\u03b3, and AMPK proteins in ZDF rats. Conclusions: In summary, QHTTF exerted a significant effect in improving glycolipid metabolism disorders of ZDF rats, which might show therapeutic effects by relieving insulin resistance, mitigating inflammation and oxidative damage, regulating related glucose, fatty acid, and amino acid metabolism, and increasing the expression of PPAR\u03b1, PPAR\u03b3, and AMPK proteins by combining network analysis, metabolomics, and biological research.<\/jats:p>","DOI":"10.3390\/ph18091347","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T08:40:15Z","timestamp":1757407215000},"page":"1347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect and Mechanism of Qihua Tongtiao Formula (QHTTF) on Improving Glucose and Lipid Metabolism Disorders in ZDF Rats by Integrating Network Pharmacology, Metabolomics, and Biological Validation"],"prefix":"10.3390","volume":"18","author":[{"given":"Yuhua","family":"Jiang","sequence":"first","affiliation":[{"name":"Institute of Basic Theory of Traditional Chinese Medicine, China Academic of Chinese Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Chinese Internal Medicine, Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajing","family":"Pan","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory of Traditional Chinese Medicine, China Academic of Chinese Medical Sciences, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Binghan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory of Traditional Chinese Medicine, China Academic of Chinese Medical Sciences, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeteng","family":"Jing","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory of Traditional Chinese Medicine, China Academic of Chinese Medical Sciences, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5575-3010","authenticated-orcid":false,"given":"Jingjing","family":"Lei","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory of Traditional Chinese Medicine, China Academic of Chinese Medical Sciences, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory of Traditional Chinese Medicine, China Academic of Chinese Medical Sciences, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinsheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory of Traditional Chinese Medicine, China Academic of Chinese Medical Sciences, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1021\/acs.jafc.1c07441","article-title":"Glycolipid Metabolism and Metagenomic Analysis of the Therapeutic Effect of a Phenolics-Rich Extract from Noni Fruit on Type 2 Diabetic Mice","volume":"70","author":"Wang","year":"2022","journal-title":"J. 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