{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T04:29:49Z","timestamp":1786768189897,"version":"build-2736575974"},"reference-count":119,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Astragalus species have long been recognized for their pharmacological relevance, yet the antidiabetic properties of Astragalus cruciatus Link (Ac) remain poorly explored. This study aimed to investigate the antidiabetic potential of A. cruciatus Link and to elucidate possible underlying mechanisms. The ethanolic extract of Ac (AcEE) was prepared and analyzed for phenolic and flavonoid content. Antioxidant activity was assessed through a series of in vitro assays. The in vitro inhibition of \u03b1-amylase and \u03b1-glucosidase was assessed, followed by molecular docking to probe ligand-enzyme interactions. LC-ESI-MS analysis revealed a polyphenol-rich profile, with rutin (953.54 \u00b5g\/g extract) and quinic acid (797.18 \u00b5g\/g of extract) identified as main compounds. The AcEE showed significant inhibitory activity against both \u03b1-amylase and \u03b1-glucosidase (IC50 = 239.30 \u00b1 7.40 and 192.60 \u00b1 15.51 \u03bcg\/mL, respectively). Moreover, low cytotoxic effects were observed in hepatic cell lines. Computational analysis revealed stable interactions between rutin and both enzymes (\u221212.935 and \u22128.073 Kcal\/mol, respectively). Network pharmacology revealed that AcEE may modulate key targets, including IL-6, TNF-\u03b1, IL-1\u03b2, Akt-1, STAT3, EGFR, and INSR as well as pathways related to insulin resistance, AGE-RAGE, and inflammation. These findings suggest that AcEE exerts significant antidiabetic effects through multitarget modulation, highlighting its potential as a natural therapeutic agent for T2DM.<\/jats:p>","DOI":"10.3390\/molecules31162831","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:01:35Z","timestamp":1786640495000},"page":"2831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phytochemical Profiling, In Vitro Bioactivity, and Network Pharmacology of Astragalus cruciatus Link Ethanolic Extract: Multitarget Mechanisms Underlying Potential Antidiabetic Effects"],"prefix":"10.3390","volume":"31","author":[{"given":"Leila","family":"Bellebcir","sequence":"first","affiliation":[{"name":"Laboratory of Genetics, Biotechnology and Bio-Resources Valorization, Department of Biology, Faculty of Exact Sciences and Natural Life Sciences, Mohamed Khider University, P.O. Box 145 RP, Biskra 07000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5375-2996","authenticated-orcid":false,"given":"Imene","family":"Derardja","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Exact Sciences and Natural Life Sciences, Mohamed Khider University, P.O. Box 145 RP, Biskra 07000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2366-7639","authenticated-orcid":false,"given":"Redouane","family":"Rebai","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Exact Sciences and Natural Life Sciences, Mohamed Khider University, P.O. Box 145 RP, Biskra 07000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Jasmin","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University of California, San Francisco, 707 Parnassus Ave Suite D-1201, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdennacer","family":"Boudah","sequence":"additional","affiliation":[{"name":"National Higher School of Biotechnology, Constantine 25000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shah, A.B., Baiseitova, A., Amzeyeva, U., Shang, X., and Jenis, J. (2025). \u03b1-Glucosidase Inhibition-Guided Network Pharmacology and Molecular Docking Reveal the Antidiabetic Potential of Cichorium intybus as a Functional Food. Int. J. Mol. 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