{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:49:55Z","timestamp":1791920995769,"version":"4.3.4"},"reference-count":37,"publisher":"Korean Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T00:00:00Z","timestamp":1704240000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010274","name":"Daegu Gyeongbuk Institute of Science and Technology","doi-asserted-by":"publisher","award":["21-BT-06"],"award-info":[{"award-number":["21-BT-06"]}],"id":[{"id":"10.13039\/501100010274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1A2C1011314"],"award-info":[{"award-number":["2021R1A2C1011314"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1C1B6008955"],"award-info":[{"award-number":["2018R1C1B6008955"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2024,1,31]]},"abstract":"<jats:p>Background: Renal fibrosis is characterized by the accumulation of extracellular matrix proteins and interstitial fibrosis. Alantolactone is known to exert anticancer, anti-inflammatory, antimicrobial and antifungal effects; however, its effects on renal fibrosis remains unknown. Here, we investigated whether alantolactone attenuates renal fibrosis in mice unilateral ureteral obstruction (UUO) and evaluated the effect of alantolactone on transforming growth factor (TGF) signaling pathway in renal cells.Methods: To evaluate the therapeutic effect of alantolactone, cell counting kit-8 (CCK-8) assay, histological staining, Western blot analysis, and real-time quantitative polymerase chain reaction were performed in UUO kidneys &lt;i&gt;in vivo&lt;\/i&gt; and in TGF-\u03b2-treated renal cells &lt;i&gt;in vitro&lt;\/i&gt;.Results: Alantolactone (0.25 to 4 \u00b5M) did not affect the viability of renal cells. Mice orally administered 5 mg\/kg of alantolactone daily for 15 days did not show mortality or liver toxicity. Alantolactone decreased UUO-induced blood urea nitrogen and serum creatinine levels. In addition, it significantly alleviated renal tubulointerstitial damage and fibrosis and decreased collagen type I, fibronectin, and \u03b1-smooth muscle actin (\u03b1-SMA) expression in UUO kidneys. In NRK-49F cells, alantolactone inhibited TGF-\u03b2stimulated expression of fibronectin, collagen type I, plasminogen activator inhibitor-1 (PAI-1), and \u03b1-SMA. In HK-2 cells, alantolactone inhibited TGF-\u03b2-stimulated expression of collagen type I and PAI-1. Alantolactone inhibited UUO-induced phosphorylation of Smad3 in UUO kidneys. In addition, it not only decreased TGF-\u03b2 secretion but also Smad3 phosphorylation and translocation to nucleus in both kidney cell lines.Conclusion: Alantolactone improves renal fibrosis by inhibiting the TGF-\u03b2\/Smad3 signaling pathway in obstructive nephropathy. Thus, alantolactone is a potential therapeutic agent for chronic kidney disease.<\/jats:p>","DOI":"10.4093\/dmj.2022.0231","type":"journal-article","created":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T08:13:30Z","timestamp":1704356010000},"page":"72-82","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Alantolactone Attenuates Renal Fibrosis via Inhibition of Transforming Growth Factor \u03b2\/Smad3 Signaling Pathway"],"prefix":"10.4093","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3962-131X","authenticated-orcid":true,"given":"Kyeong-Min","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8031-7686","authenticated-orcid":true,"given":"Yeo Jin","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwon-Soo","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2567","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-011-1772-6"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2011.149"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2010080793"},{"key":"ref4","first-page":"689","volume-title":"Transforming growth factor-beta regulates production of proteoglycans by mesangial cells","author":"Border","year":"1990"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00082"},{"key":"ref6","first-page":"1213","volume-title":"Production of extracellular matrix by glomerular epithelial cells is regulated by transforming growth factor-beta 1","author":"Nakamura","year":"1992"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.5483\/bmbrep.2020.53.11.153"},{"key":"ref8","first-page":"225","volume-title":"Transforming growth factor-beta: major role in regulation of extracellular matrix","author":"Roberts","year":"1990"},{"key":"ref9","first-page":"15","volume-title":"TGF-beta signaling by Smad proteins","author":"Miyazono","year":"2000"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2011.06.002"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2009.009218"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2014040363"},{"key":"ref13","first-page":"1527","volume-title":"Inhibition of p38 mitogen-activated protein kinase and transforming growth factor-beta1\/Smad signaling pathways modulates the development of fibrosis in adriamycin-induced nephropathy","author":"Li","year":"2006"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1159\/000345990"},{"key":"ref15","first-page":"672","volume-title":"","author":"Hoffmann","year":"2003"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/248532"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2012.08.011"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.2521"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2020.1725039"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5804"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104065"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2010080890"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-018-0510-x"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3390\/molecules20057719"},{"key":"ref25","first-page":"156","volume-title":"High body clearance and low oral bioavailability of alantolactone, isolated from Inula helenium, in rats: extensive hepatic metabolism and low stability in gastrointestinal fluids","author":"Lee","year":"2016"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.4511"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-017-0563-8"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6004"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14139"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.86"},{"key":"ref31","first-page":"587","volume-title":"Attenuation of renal fibrosis by proteasome inhibition in rat obstructive nephropathy: possible role of nuclear factor kappaB","author":"Tashiro","year":"2003"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1172\/jci200319270"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1002\/path.3976"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1181-y"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/719858"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00595.2020"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2015.03.061"}],"container-title":["Diabetes &amp; 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