{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T23:04:33Z","timestamp":1784329473235,"version":"3.55.0"},"reference-count":43,"publisher":"Institute of Physiology of the Czech Academy of Sciences","issue":"3\/2025","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiol Res"],"abstract":"<jats:p>Sepsis-induced acute kidney injury (SAKI) is one of the most frequent complications in patients with sepsis and is strongly associated with poor clinical outcomes. Trigonelline (TRL), a bioactive pyridine alkaloid isolated from fenugreek, has exhibited therapeutic effects on various diseases. This study aimed to investigate the effects of TRL on SAKI and whether TRL exerted its function via NAD+\/SIRT1 pathway activation. A single dose (10 mg\/kg body weight) of lipopolysaccharide (LPS) was intraperitoneally administered to establish a mouse SAKI model. After 24 h, compared with the control group, the plasma levels of kidney function indicators creatinine and blood urea nitrogen, oxidative stress indicators hydrogen peroxide and malondialdehyde, and inflammatory factors tumor necrosis factor-\u03b1 and interleukin-1\u03b2 were significantly increased. Meanwhile, hematoxylin and eosin staining results revealed that LPS treatment caused glomerular structure disruption, renal tubular luminal narrowing, and renal tubular structure deterioration. TRL treatment significantly reduced the plasma kidney function indicators, oxidative stress, and inflammatory factors levels in the SAKI mice, accompanied by improvements in the renal pathological changes. Furthermore, TRL treatment increased the NAD+ levels, upregulated the SIRT1 expression, and downregulated the NOX4 expression in the kidney of the SAKI mice. Subsequently, EX-527, a selective SIRT1 inhibitor, was used for inhibiting SIRT1, and it reversed the protective effect of TRL in SAKI. Our results revealed that TRL improved renal function and alleviated inflammation and oxidative stress in SAKI mice by NAD+\/SIRT1 pathway activation. Therefore, TRL may be a potential therapeutic approach for SAKI treatment.<\/jats:p>","DOI":"10.33549\/physiolres.935486","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T09:37:54Z","timestamp":1753263474000},"page":"439-447","source":"Crossref","is-referenced-by-count":4,"title":["Trigonelline Attenuated Sepsis-Induced Acute Kidney Injury by Activating NAD+\/SIRT1 Pathway"],"prefix":"10.33549","author":[{"given":"W","family":"Lv","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"19169","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"1.\tCecconi M, Evans L, Levy M, Rhodes A. 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Kidney Int 2023;104:305-323. https:\/\/doi.org\/10.1016\/j.kint.2023.04.013","DOI":"10.1016\/j.kint.2023.04.013"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"18.\tLi T, Sun H, Li Y, Su L, Jiang J, Liu Y, Jiang N, et al. Downregulation of macrophage migration inhibitory factor attenuates NLRP3 inflammasome mediated pyroptosis in sepsis-induced AKI. Cell Death Discov 2022;8:61. https:\/\/doi.org\/10.1038\/s41420-022-00859-z","DOI":"10.1038\/s41420-022-00859-z"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"19.\tYu YY, Li XQ, Hu WP, Cu SC, Dai JJ, Gao YN, Zhang YT, et al. Self-developed NF-\u03baB inhibitor 270 protects against LPS-induced acute kidney injury and lung injury through improving inflammation. 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Effects of Trigonelline, an Alkaloid Present in Coffee, on Diabetes-Induced Disorders in the Rat Skeletal System. Nutrients 2016;8:133. https:\/\/doi.org\/10.3390\/nu8030133","DOI":"10.3390\/nu8030133"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"23.\tLi Y, Li Q, Wang C, Lou Z, Li Q. Trigonelline reduced diabetic nephropathy and insulin resistance in type 2 diabetic rats through peroxisome proliferator-activated receptor-\u03b3. Exp Ther Med 2019;18:1331-1337. https:\/\/doi.org\/10.3892\/etm.2019.7698","DOI":"10.3892\/etm.2019.7698"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"24.\tPeerapen P, Boonmark W, Thongboonkerd V. Trigonelline prevents kidney stone formation processes by inhibiting calcium oxalate crystallization, growth and crystal-cell adhesion, and downregulating crystal receptors. 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Int Immunopharmacol 2018;61:355-362. https:\/\/doi.org\/10.1016\/j.intimp.2018.06.019","DOI":"10.1016\/j.intimp.2018.06.019"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"30.\tJiang J, Huang K, Xu S, Garcia JGN, Wang C, Cai H. Targeting NOX4 alleviates sepsis-induced acute lung injury via attenuation of redox-sensitive activation of CaMKII\/ERK1\/2\/MLCK and endothelial cell barrier dysfunction. Redox Biol 2020;36:101638. https:\/\/doi.org\/10.1016\/j.redox.2020.101638","DOI":"10.1016\/j.redox.2021.102200"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"31.\tYoo JY, Cha DR, Kim B, An EJ, Lee SR, Cha JJ, Kang YS, et al. LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1. Cell Rep 2020;33:108245. https:\/\/doi.org\/10.1016\/j.celrep.2020.108245","DOI":"10.1016\/j.celrep.2020.108245"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"32.\tLi J, Wang L, Wang B, Zhang Z, Jiang L, Qin Z, Zhao Y, Su B. NOX4 is a potential therapeutic target in septic acute kidney injury by inhibiting mitochondrial dysfunction and inflammation. Theranostics 2023;13:2863-2878. https:\/\/doi.org\/10.7150\/thno.81240","DOI":"10.7150\/thno.81240"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"33.\tYoshinari O, Takenake A, Igarashi K. Trigonelline ameliorates oxidative stress in type 2 diabetic Goto-Kakizaki rats. J Med Food 2013;16:34-41. https:\/\/doi.org\/10.1089\/jmf.2012.2311","DOI":"10.1089\/jmf.2012.2311"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"34.\tLi HR, Liu Q, Zhu CL, Sun XY, Sun CY, Yu CM, Li P, et al. \u03b2-Nicotinamide mononucleotide activates NAD+\/SIRT1 pathway and attenuates inflammatory and oxidative responses in the hippocampus regions of septic mice. 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Nat Metab 2024;6:433-447. https:\/\/doi.org\/10.1038\/s42255-024-00997-x","DOI":"10.1038\/s42255-024-00997-x"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"40.\tGertz M, Fischer F, Nguyen GT, Lakshminarasimhan M, Schutkowski M, Weyand M, Steegborn C. Ex-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism. Proc Natl Acad Sci U S A 2013;110:E2772-E2781. https:\/\/doi.org\/10.1073\/pnas.1303628110","DOI":"10.1073\/pnas.1303628110"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"41.\tLi HR, Liu Q, Zhu CL, Sun XY, Sun CY, Yu CM, Li P, et al. \u03b2-Nicotinamide mononucleotide activates NAD+\/SIRT1 pathway and attenuates inflammatory and oxidative responses in the hippocampus regions of septic mice. 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Redox Biol 2021;38:101813. https:\/\/doi.org\/10.1016\/j.redox.2020.101813","DOI":"10.1016\/j.redox.2020.101813"}],"container-title":["Physiological Research"],"original-title":[],"language":"en","deposited":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T09:37:57Z","timestamp":1753263477000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.biomed.cas.cz\/physiolres\/pdf\/2025\/74_439.pdf"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,21]]},"references-count":43,"journal-issue":{"issue":"3\/2025","published-online":{"date-parts":[[2025,7,21]]}},"URL":"https:\/\/doi.org\/10.33549\/physiolres.935486","relation":{},"ISSN":["1802-9973","0862-8408"],"issn-type":[{"value":"1802-9973","type":"electronic"},{"value":"0862-8408","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7,21]]}}}