{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T03:23:04Z","timestamp":1786591384913,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jilin province science and technology development plan","award":["YDZJ202101ZYTS095"],"award-info":[{"award-number":["YDZJ202101ZYTS095"]}]},{"name":"Science and Technology Project of the Education Department of Jilin Province","award":["JJKH20240593KJ"],"award-info":[{"award-number":["JJKH20240593KJ"]}]},{"name":"Jilin Province Health Technology Capability Improvement Project","award":["2023JC050"],"award-info":[{"award-number":["2023JC050"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The chemical composition of the ethanol extract of Acanthopanax senticosus fruit (ASFEE) was systematically characterized using UPLC-MS\/MS (Q Exactive Orbitrap), leading to the identification of 45 compounds. Through integrated network pharmacology and molecular docking analyses, the binding affinities between key bioactive constituents\u2014such as eleutheroside E (EE) and quercetin\u2014and core therapeutic targets were predicted and validated. A total of 125 overlapping targets were identified between ASFEE and acute kidney injury (AKI), with significant enrichment observed in critical signaling pathways, including NF-\u03baB, IL-17, and PI3K-Akt. To evaluate the protective effects of ASFEE, both in vitro (HK-2 cells) and in vivo (murine) models of cisplatin (DDP)-induced AKI were employed. Parameters assessed included cell viability, apoptosis, reactive oxygen species (ROS) production, activation of the NF-\u03baB signaling pathway, kidney function, histopathological alterations, and levels of inflammatory cytokines. ASFEE treatment markedly enhanced HK-2 cell viability and reduced cellular apoptosis and ROS generation. In the murine model, DDP administration resulted in significantly elevated serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Both low- and high-dose ASFEE treatments significantly attenuated these increases, improved overall kidney function, and alleviated kidney tubular damage. Furthermore, ASFEE reduced serum levels of pro-inflammatory cytokines, including IL-1\u03b2, IL-6, and TNF-\u03b1. Multi-omics integration analysis enabled the identification of differentially expressed genes and metabolites. ASFEE was found to reverse 4689 DDP-induced gene expression changes and 323 metabolic disturbances, with the uridine diphosphate glucuronosyltransferase (UGT)-mediated ascorbic acid metabolism pathway emerging as the central regulatory axis. Key candidate genes and proteins were further validated via real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. DDP significantly upregulated the expression of inflammatory markers and associated signaling molecules in kidney tissues, while concurrently downregulating UGT family genes and the UGT1A1 protein involved in uronic acid metabolism. Notably, ASFEE treatment effectively counteracted these alterations, confirming its role in enhancing UGT1A1-mediated metabolic processes and suppressing the NF-\u03baB\/PI3K-Akt\/IL-17 signaling cascade. These mechanisms contribute to improved antioxidant capacity, mitigation of inflammatory responses, and restoration of metabolic homeostasis, thereby conferring protection against DDP-induced AKI. ASFEE exerts a protective effect on AKI caused by DDP by enhancing antioxidant capacity, inhibiting inflammation and restoring metabolic homeostasis, providing an experimental basis for its subsequent development and application.<\/jats:p>","DOI":"10.3390\/ijms262211131","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T09:58:42Z","timestamp":1763459922000},"page":"11131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative Transcriptomic and Metabolomic Analysis Reveals That Acanthopanax senticosus Fruit Ameliorates Cisplatin-Induced Acute Kidney Injury by Suppressing the NF-\u03baB\/PI3K-AKT Pathway via UGT1A1 Regulation"],"prefix":"10.3390","volume":"26","author":[{"given":"Liu","family":"Han","sequence":"first","affiliation":[{"name":"College of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zebo","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0964-4191","authenticated-orcid":false,"given":"Xiangyu","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jilin Medical University, Jilin 132013, China"},{"name":"College of Pharmacy, Yanbian University, Yanji 133002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2390-6257","authenticated-orcid":false,"given":"Yu","family":"Han","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Bian","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liancong","family":"Gao","sequence":"additional","affiliation":[{"name":"Clinical Medical College, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengran","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eabf5074","DOI":"10.1126\/scitranslmed.abf5074","article-title":"Endothelin blockade prevents the long-term cardiovascular and kidney sequelae of acute kidney injury in mice","volume":"14","author":"Czopek","year":"2022","journal-title":"Sci. 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