{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:10:10Z","timestamp":1779376210701,"version":"3.53.1"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Karamay Science and Technology Plan Project","award":["2025BA0090"],"award-info":[{"award-number":["2025BA0090"]}]},{"name":"Doctoral Science Foundation of Xinjiang Second Medical College","award":["XGYK2025-102"],"award-info":[{"award-number":["XGYK2025-102"]}]},{"name":"Liver disease pathogenesis and prevention research innovation team","award":["KT202604"],"award-info":[{"award-number":["KT202604"]}]},{"name":"Scientific research project of Xinjiang Second Medical College"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Astragalus root, a traditional Chinese herbal remedy, has shown potential benefits against diabetic nephropathy (DN). However, the mechanisms driving its effects remain poorly understood. This study explored the molecular pathways through which Astragalus root improves DN. To identify possible targets and mechanisms of Astragalus root in DN treatment, we applied network pharmacology, molecular docking, molecular dynamics simulation, and in vitro assays. Network pharmacology screening uncovered 46 overlapping targets between Astragalus root and DN. Protein\u2013protein interaction (PPI) network analysis identified five core candidate targets: CASP3, VEGFA, CTNNB1, MYC, and PRKCB (PKC\u03b2). KEGG pathway analysis indicated that the AGE-RAGE signaling pathway was the most significantly enriched. Molecular docking revealed that quercetin, \u03b2-carotene, daidzein, capsaicin, and kaempferol\u2014potential bioactive components of Astragalus root\u2014bound strongly to each of the five core targets. Molecular dynamics simulations further confirmed the conformational stability of kaempferol when complexed with these target proteins. In vitro experiments showed that kaempferol markedly reduced protein levels of \u03b1-SMA, Col I, and Col IV; lowered secretion of TNF-\u03b1, IL-6, and IL-1\u03b2; and decreased ROS and MDA content. Additionally, kaempferol\u2019s therapeutic effects were mediated through suppression of the AGE-RAGE-PKC\u03b2-TGF-\u03b21 signaling axis. This work identified kaempferol, a bioactive ingredient of Astragalus root, as a potential therapeutic agent against DN, along with its target pathways. These findings provide a scientific foundation for its clinical translation.<\/jats:p>","DOI":"10.3390\/ijms27104641","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:02:27Z","timestamp":1779375747000},"page":"4641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the Effects and Potential Mechanisms of Astragalus Root Against Diabetic Nephropathy Based on Bioinformatics Analysis and In Vitro Validation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1850-8902","authenticated-orcid":false,"given":"Jie","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy, Xinjiang Second Medical College, Karamay 834000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subinur","family":"Ahmattohti","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Second Medical College, Karamay 834000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Gao","sequence":"additional","affiliation":[{"name":"Science and Innovation Center of Xinjiang Second Medical College, Karamay 834000, China"},{"name":"Shaanxi Collaborative Innovation Center of Chinese Medicine Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangqin","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Second Medical College, Karamay 834000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasur","family":"Kasim","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Second Medical College, Karamay 834000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8369-2787","authenticated-orcid":false,"given":"Liang","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinjiang Second Medical College, Karamay 834000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baojian","family":"Li","sequence":"additional","affiliation":[{"name":"Science and Innovation Center of Xinjiang Second Medical College, Karamay 834000, China"},{"name":"Shaanxi Collaborative Innovation Center of Chinese Medicine Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuliang","family":"Niu","sequence":"additional","affiliation":[{"name":"Science and Innovation Center of Xinjiang Second Medical College, Karamay 834000, China"},{"name":"School of Basic Medical Sciences, Xinjiang Second Medical College, Karamay 834000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Second Medical College, Karamay 834000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.4239\/wjd.v15.i6.1111","article-title":"Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies","volume":"15","author":"Zhou","year":"2024","journal-title":"World J. 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