{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T10:40:17Z","timestamp":1786790417480,"version":"build-2736575974"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":252,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Program of Zhejiang Provincial TCM Sci-Tech Plan","award":["2021ZB110"],"award-info":[{"award-number":["2021ZB110"]}]},{"name":"Program of Zhejiang Provincial TCM Sci-Tech Plan","award":["2020ZB075"],"award-info":[{"award-number":["2020ZB075"]}]},{"name":"Program of Zhejiang Provincial TCM Sci-Tech Plan","award":["2019ZQ021"],"award-info":[{"award-number":["2019ZQ021"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Acute kidney injury (AKI) is responsible for significant mortality among hospitalized patients that is especially troubling aged people. An effective self\u2010made Chinese medicine formula, Xiaoyu Xiezhuo Drink (XXD), displayed therapeutic effects on AKI. However, the compositions and underlying mechanisms of XXD remain to be elucidated. In this study, we used the ultra\u2010high\u2010performance liquid chromatography method coupled with hybrid triple quadrupole time\u2010of\u2010flight mass spectrometry (UHPLC\u2010Q\u2010TOF\u2010MS) to investigate the chemical components in XXD. Then, the absorbable components of XXD were identified based on the five principles and inputted into the SwissTargetPrediction and STITCH databases to identify the drug targets. AKI\u2010related targets were collected from the GenCLiP 3, GeneCards, and DisGeNET databases. The crossover genes of XXD and AKI were identified for functional enrichment analysis. The protein\u2010protein interaction (PPI) network of crossover genes was constructed, followed by the identification of hub genes. Subsequently, the effects and potential mechanisms of XXD on AKI predicted by the network pharmacology and bioinformatics analyses were experimentally validated in ischemia\u2010reperfusion (I\/R) injury\u2010induced AKI aged mouse models. A total of 122 components in XXD were obtained; among them, 58 components were found that could be absorbed in the blood. There were 800 potential drug targets predicted from the 58 absorbable components in AKI which shared 36 crossover genes with AKI\u2010related targets. The results of functional enrichment analysis indicated that crossover genes mostly associated with the response to oxidative stress and the HIF1 signaling pathway. In the PPI network analysis, 12 hub genes were identified, including ALB, IL\u20106, TNF, TP53, VEGFA, PTGS2, TLR4, NOS3, EGFR, PPARG, HIF1A, and HMOX1. In AKI aged mice, XXD prominently alleviated I\/R injury\u2010induced renal dysfunction, abnormal renal pathological changes, and cellular senescence, inflammation, and oxidative damage with a reduction in the expression level of the inflammatory mediator, <jats:italic>\u03b1<\/jats:italic>\u2010SMA, collagen\u20101, F4\/80, TP53, VEGFA, PTGS2, TLR4, NOS3, EGFR, PPARG, HIF1A, ICAM\u20101, TGF\u2010<jats:italic>\u03b2<\/jats:italic>1, Smad3, and p\u2010Smad3 and an increase of nephridial tissue p\u2010H3, Ki67, HMOX1, MMP\u20109, and Smad7 levels. In summary, our findings suggest that XXD has renoprotective effects against AKI in aged mice via inhibiting the TGF\u2010<jats:italic>\u03b2<\/jats:italic>1\/Smad3 and HIF1 signaling pathways.<\/jats:p>","DOI":"10.1155\/2021\/9963732","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T20:35:09Z","timestamp":1631306109000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Xiaoyu Xiezhuo Drink Protects against Ischemia\u2010Reperfusion Acute Kidney Injury in Aged Mice through Inhibiting the TGF\u2010<i>\u03b2<\/i>1\/Smad3 and HIF1 Signaling 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