{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:16:16Z","timestamp":1792653376798,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":321,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973831"],"award-info":[{"award-number":["81973831"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2020YFS0367"],"award-info":[{"award-number":["2020YFS0367"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Acute kidney injury (AKI) is a common clinically critical illness with serious consequences for the patients. Shenshuaikang enema (SE) is a Chinese herbal compound that is used to treat AKI in clinical practice. However, its mechanism of action remains unclear. <jats:italic>Aim<\/jats:italic>. The aim of this study was to investigate the therapeutic effect of SE and explore the molecular mechanisms using network pharmacology and in vitro experiments. <jats:italic>Materials and Methods<\/jats:italic>. The herb\u2010component\u2010target network was constructed based on network pharmacology. The predicted targets and pathways were validated using in vitro experiments. A renal tubular epithelial cell line (HK\u20102 cells) was exposed to hypoxia and reoxygenation (H\/R) using air\u2010tight conditions for five hours and treated with different concentrations of SE (25%, 50%, and 75%) to assess cell viability and apoptosis and determine the optimal experimental dose. Subsequently, H\/R\u2010injured HK\u20102 cells were pretreated with the optimal SE dose and then randomly divided into three groups, the SE, SE\u2010SP600125 (inhibitor of JNK), and SE\u2010NAC (antioxidant) groups. The cell vitality, apoptosis, and death were evaluated using the cell counting kit 8 (CCK8) and carboxyfluorescein succinimidyl ester\/propidium iodide (CFSF\/PI) staining. The apoptosis\u2010related protein JNK and Caspase\u20103 were assessed by Western blot. Expression of JNK and Caspase\u20103 genes was analyzed using real\u2010time quantitative polymerase chain reaction (RT\u2010qPCR). <jats:italic>Results<\/jats:italic>. 123 active components and 226 targets were identified from four herbs that composed the herb\u2010compound\u2010target network based on transcriptomics and network pharmacology analyses. The KEGG pathway analyses revealed that the mitochondrial apoptosis pathway was involved in the therapeutic AKI effects of SE. Cell vitality of H\/R\u2010induced HK\u20102 cells was obviously increased when treating them with SE, and the apoptosis was significantly inhibited, especially in the SE (50%) group at 4 and 12\u2009h after modeling. Pretreatment with antioxidant NAC obviously prevented cell death compared to the SE (50%) group, while no obvious reduction of apoptosis was observed in the SP600125 group. JNK expression level was significantly increased in the SE (50%) group compared to the SP600125 (<jats:italic>P<\/jats:italic> &lt; 0.01) and the NAC group (<jats:italic>P<\/jats:italic> &lt; 0.05). Caspase\u20103 was downregulated in the SE (50%) group compared to the SP600125 (<jats:italic>P<\/jats:italic> &lt; 0.01) and NAC group (<jats:italic>P<\/jats:italic> &lt; 0.05). Caspase\u20103 activation in the SP600125 group was higher than that in the NAC group (<jats:italic>P<\/jats:italic> &lt; 0.05). Moreover, the oxidative damage\u2010dependent JNK\/Caspase\u20103 pathway was identified in the H\/R\u2010injured HK\u20102 cells by inhibiting the JNK activation and oxidative damage. <jats:italic>Conclusions<\/jats:italic>. Our findings suggested that the H\/R\u2010triggered apoptosis in HK\u20102 cells was abrogated by SE by upregulating the oxidative damage\u2010dependent JNK to trigger suppression of Caspase\u20103.<\/jats:p>","DOI":"10.1155\/2020\/9457101","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T19:05:07Z","timestamp":1605639907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Shenshuaikang Enema, a Chinese Herbal Remedy, Inhibited Hypoxia and Reoxygenation\u2010Induced Apoptosis in Renal Tubular Epithelial Cells by Inhibiting Oxidative Damage\u2010Dependent JNK\/Caspase\u20103 Signaling Pathways Using Network 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