{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:25:11Z","timestamp":1787160311465,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32260103"],"award-info":[{"award-number":["32260103"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012579","name":"Natural Science Foundation of Qinghai Province","doi-asserted-by":"publisher","award":["2023-ZJ-939M"],"award-info":[{"award-number":["2023-ZJ-939M"]}],"id":[{"id":"10.13039\/501100012579","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>An integrative approach combining network pharmacology, molecular docking, and cellular assays was used to elucidate the potential mechanisms by which the n-butanol extract of Biebersteinia heterostemon ameliorates type 2 diabetes mellitus (T2DM). Chemical constituents of the n-butanol extract were identified via ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry. Active compounds and T2DM-related targets were retrieved from public databases, and intersecting targets were identified. Protein\u2013protein interaction (PPI) networks were constructed using the STRING database, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed via the DAVID database. A comprehensive \u201cdrug\u2013compound\u2013target\u2013disease\u2013pathway\u201d network was established, and molecular docking was conducted to evaluate binding affinities of key compounds to core targets. Functional validation was performed in insulin-resistant cell models. Network pharmacology analysis identified 37 active constituents within the extract and 222 overlapping targets associated with T2DM. GO enrichment indicated involvement in protein phosphorylation, MAPK cascade activation, and negative regulation of apoptosis. Key signaling pathways included PI3K\/AKT and lipid and atherosclerosis pathways. Molecular docking revealed strong binding affinities (binding energies \u2264 \u22129.3 kcal\u00b7mol\u22121) between core compounds\u2014such as cheilanthifoline, glabridin, acetylcorynoline, skullcapflavone II, liquiritigenin, and dinatin\u2014and pivotal targets including GAPDH, AKT1, TNF, SRC, EGFR, and PPAR\u03b3. In vitro experiments demonstrated that the extract significantly enhanced glucose uptake and glycogen synthesis in insulin-resistant cells, while suppressing oxidative stress and the expression of pro-inflammatory mediators such as TNF-\u03b1, MMP9, and IL-6. Collectively, B. heterostemon shows potential as an effective intervention for T2DM by targeting key molecular pathways, improving insulin sensitivity, and mitigating oxidative stress and inflammation in insulin-resistant cells.<\/jats:p>","DOI":"10.3390\/ijms26209866","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:50:16Z","timestamp":1760107816000},"page":"9866","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the Mechanisms of n-Butanol Extract from Tibetan Medicine Biebersteinia heterostemon in Improving Type 2 Diabetes Based on Network Pharmacology and Cellular Experiments"],"prefix":"10.3390","volume":"26","author":[{"given":"Shengwen","family":"Chen","sequence":"first","affiliation":[{"name":"College of Eco-Environmental Engineering, Qinghai University, Xining 810016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Eco-Environmental Engineering, Qinghai University, Xining 810016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuxiu","family":"Shen","sequence":"additional","affiliation":[{"name":"College of Eco-Environmental Engineering, Qinghai University, Xining 810016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7672-6666","authenticated-orcid":false,"given":"Benyin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Eco-Environmental Engineering, Qinghai University, Xining 810016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1016\/S0140-6736(24)02317-1","article-title":"Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: A pooled analysis of 1108 population-representative studies with 141 million participants","volume":"404","author":"Zhou","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Duncan, B.B., Magliano, D.J., and Boyko, E.J. 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