{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:56:48Z","timestamp":1782939408028,"version":"3.54.5"},"reference-count":42,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Abnormal and excessive growth of mesangial cells is important in the pathophysiologic processes of diabetes-associated interstitial fibrosis and glomerulosclerosis, leading to diabetic nephropathy, which eventually turns into end-stage renal disease. Sauchinone, a biologically-active lignan isolated from aerial parts of Saururus chinensis, has anti-inflammatory and anti-viral activities effects on various cell types. However, there are no studies reporting the effects of sauchinone on diabetic nephropathy. The present study aims to investigate the role of sauchinone in mesangial cell proliferation and fibrosis induced by angiotensin II, as well as the underlying mechanisms of these processes. Human renal mesangial cells were induced by angiotensin II (AngII, 10\u202f\u03bcM) in the presence or absence of sauchinone (0.1\u20131\u202f\u03bcM) and incubated for 48\u202fh. In this study, we found that AngII induced mesangial cell proliferation, while treatment with sauchinone inhibited the cell proliferation in a dose-dependent manner. Pre-treatment with sauchinone induced down-regulation of cyclins\/CDKs and up-regulation of CDK inhibitor, p21, and p27kip1 expression. In addition, AngII-enhanced expression of fibrosis biomarkers such as fibronectin, collagen IV, and connective tissue growth factor (CTGF), which was markedly attenuated by sauchinone. Sauchinone also decreased AngII-induced TGF-\u03b21 and Smad-2, Smad-3, and Smad-4 expression. This study further revealed that sauchinone ameliorated AngII-induced mesangial inflammation through disturbing activation of inflammatory factors, and NLRP3 inflammasome, which is composed of the NLRP3 protein, procaspase-1, and apoptosis-associated speck-like protein containing a CARD (ASC). Moreover, pretreatment of sauchinone inhibited NF-\u03baB translocation and ROS production in AngII-exposed mesangial cells. These data suggest that sauchinone has a protective effect on renal proliferation, fibrosis and inflammation. Therefore, sauchinone might be a potential pharmacological agent in prevention of AngII-induced renal damage leading to diabetic nephropathy.<\/jats:p>","DOI":"10.3390\/ijms21197003","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T09:28:08Z","timestamp":1600853288000},"page":"7003","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Sauchinone Protects Renal Mesangial Cell Dysfunction against Angiotensin II by Improving Renal Fibrosis and Inflammation"],"prefix":"10.3390","volume":"21","author":[{"given":"Jung Joo","family":"Yoon","sequence":"first","affiliation":[{"name":"Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"},{"name":"College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Kyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"},{"name":"College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Yoom","family":"Kim","sequence":"additional","affiliation":[{"name":"Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"},{"name":"College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Hyuk","family":"Han","sequence":"additional","affiliation":[{"name":"Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"},{"name":"College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Sub","family":"Lee","sequence":"additional","affiliation":[{"name":"Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"},{"name":"College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9347-8606","authenticated-orcid":false,"given":"Yun Jung","family":"Lee","sequence":"additional","affiliation":[{"name":"Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"},{"name":"College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Gill","family":"Kang","sequence":"additional","affiliation":[{"name":"Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"},{"name":"College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, 460, Iksan-daero, Iksan, Jeonbuk 54538, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2147\/IJNRD.S40172","article-title":"Diabetic nephropathy complications and treatment","volume":"7","author":"Lim","year":"2014","journal-title":"Int. J. Nephrol. Renovasc. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1369\/0022155412465073","article-title":"Diabetic Nephropathy and Extracellular Matrix","volume":"60","author":"Kolset","year":"2012","journal-title":"J. Histochem. Cytochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nrneph.2010.57","article-title":"New pharmacological treatments for improving renal outcomes in diabetes","volume":"6","author":"Sharma","year":"2010","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_4","first-page":"1439","article-title":"Mechanisms of Glomerulosclerosis in Diabetic Nephropathy","volume":"57","author":"Ying","year":"2008","journal-title":"Diabetes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1097\/00041552-200111000-00001","article-title":"Pathogenesis of diabetic nephropathy: Focus on transforming growth factor-beta and connective tissue growth factor","volume":"10","author":"Sakharova","year":"2001","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1159\/000480198","article-title":"Effect of huaier on the proliferation of mesangial cells in anti-thy-1 nephritis","volume":"42","author":"Bai","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1046\/j.1523-1755.2000.07715.x","article-title":"Role of angiotensin II in diabetic nephropathy","volume":"58","author":"David","year":"2000","journal-title":"Kidney Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.2174\/1381612811319170009","article-title":"Angiotensin II blockade and renal protection","volume":"19","author":"Kobori","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_9","first-page":"277","article-title":"Angiotensin II Regulation of TGF-\u03b2 in Murine Mesangial Cells Involves Both PI3 Kinase and MAP Kinase","volume":"34","author":"Alan","year":"2004","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1097\/01.ASN.0000130568.53923.FD","article-title":"Hepatocyte growth factor antagonizes the profibrotic action of TGF-beta1 in mesangial cells by stabilizing Smad transcriptional corepressor TGIF","volume":"15","author":"Dai","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.molcel.2007.11.039","article-title":"Cooperative assembly of TGF-\u03b2 superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding","volume":"29","author":"Groppe","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.7150\/ijbs.7.1056","article-title":"Diverse Roles of TGF-\u03b2\/Smads in Renal Fibrosis and Inflammation","volume":"7","author":"Lan","year":"2011","journal-title":"Int. J. Biol. Sci."},{"key":"ref_13","first-page":"1040","article-title":"Effects of pioglitazone on expressions of matrix metalloproteinases 2 and 9 in kidneys of diabetic rats","volume":"117","author":"Dong","year":"2004","journal-title":"Chin. Med. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/nrneph.2011.149","article-title":"Cellular and molecular mechanisms of renal fibrosis","volume":"7","author":"Liu","year":"2011","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.3181\/0903-RM-105","article-title":"Delayed treatment with plasminogen activator inhibitor-1 decoys reduces tubulointerstitial fibrosis","volume":"234","author":"Gonzalez","year":"2009","journal-title":"Exp. Biol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1124\/jpet.114.214205","article-title":"Astragaloside IV ameliorates renal fibrosis via the inhibition of mitogen-activated protein kinases and antiapoptosis in vivo and in vitro","volume":"350","author":"Xu","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mansour, S.G., Puthumana, J., Coca, S.G., Gentry, M., and Parikh, C.R. (2017). Biomarkers for the detection of renal fibrosis and prediction of renal outcomes: A systematic review. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0490-0"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1007\/s12020-014-0437-1","article-title":"Inflammation in diabetic nephropathy: Moving toward clinical biomarkers and targets for treatment","volume":"48","author":"Barutta","year":"2015","journal-title":"Endocrine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"466","DOI":"10.2337\/diabetes.49.3.466","article-title":"Early glomerular macrophage recruitment in streptozotocin-induced diabetic rats","volume":"49","author":"Heudes","year":"2000","journal-title":"Diabetes"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1681\/ASN.V111152","article-title":"Chemokines, chemokine receptors, and renal disease: From basic science to pathophysiologic and therapeutic studies","volume":"11","author":"Segerer","year":"2000","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S76","DOI":"10.1046\/j.1523-1755.1999.07119.x","article-title":"The central role of nuclear factor-\u03baB in mesangial cell activation","volume":"56","author":"Massy","year":"1999","journal-title":"Kidney Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1002\/j.1460-2075.1991.tb07761.x","article-title":"Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-\u03baB transcription factor and HIV-1","volume":"10","author":"Schreck","year":"1991","journal-title":"EMBO J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"F159","DOI":"10.1152\/ajprenal.00546.2013","article-title":"RhoA\/Rho kinase mediates TGF-beta1-induced kidney myofibroblast activation through Poldip2\/Nox4-derived reactive oxygen species","volume":"307","author":"Manickam","year":"2014","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.drudis.2018.08.005","article-title":"Effects of antidiabetic drugs on NLRP3 inflammasome activity, with a focus on diabetic kidneys","volume":"24","author":"Yaribeygi","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/978-981-13-8871-2_19","article-title":"Role of inflammasome in chronic kidney disease","volume":"1165","author":"Li","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.kint.2019.01.014","article-title":"Multifactorial functions of the inflammasome component NLRP3 in pathogenesis of chronic kidney diseases","volume":"96","author":"Mulay","year":"2019","journal-title":"Kidney Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41419-019-1413-8","article-title":"Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors","volume":"10","author":"Yang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1055\/s-2003-45106","article-title":"Saucernetin-7 and saucernetin-8 isolated from Saururus chinensis inhibit the LPS-induced production of nitric oxide and prostaglandin E2 in macrophage RAW264.7 cells","volume":"69","author":"Park","year":"2003","journal-title":"Planta Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1021\/np400757k","article-title":"Potential antiviral lignans from the roots of Saururus chinensis with activity against Epstein-Barr virus lytic replication","volume":"77","author":"Cui","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jep.2008.04.011","article-title":"Antihypertensive, vasorelaxant and inotropic effects of an ethanolic extract of the roots of Saururus chinensis","volume":"118","author":"Ryu","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1248\/bpb.31.523","article-title":"Protective effect of lignans against sepsis from the roots of Saururus chinensis","volume":"31","author":"Seo","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1248\/bpb.b110670","article-title":"Anti-proliferative neolignans from Saururus chinensis against human cancer cell lines","volume":"35","author":"Lee","year":"2012","journal-title":"Biol. Pharm. Bull."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/sj.bjp.0705231","article-title":"Inhibition of lipopolysaccharide-inducible nitric oxide synthase, TNF-\u03b1 and COX-2 expression by sauchinone effects on I-\u03ba phosphorylation, C\/EBP and AP-1 activation","volume":"139","author":"Lee","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0272-6386(12)80349-0","article-title":"Regulation of Mesangial Cell Proliferation","volume":"17","author":"Nicholas","year":"1991","journal-title":"Am. J. Kidney Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s10238-013-0232-y","article-title":"AngII-induced glomerular mesangial cell proliferation inhibited by losartan via changes in intracellular calcium ion concentration","volume":"14","author":"Qiu","year":"2014","journal-title":"Clin. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ou, Y.C., Li, J.R., Wang, J.D., Chang, C.Y., Wu, C.C., Chen, W.Y., Kuan, Y.H., Liao, S.L., Lu, H.C., and Chen, C.J. (2019). Fibronectin Promotes Cell Growth and Migration in Human Renal Cell Carcinoma Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112792"},{"key":"ref_37","first-page":"F707","article-title":"TGF-\u03b2 and CTGF have overlapping and distinct fibrogenic effects on human renal cells","volume":"283","author":"Elizabeth","year":"2000","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3389\/fphys.2015.00082","article-title":"TGF-\u03b2\/Smad signaling in renal fibrosis","volume":"6","author":"Meng","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yoon, J.J., Park, J.H., Kim, H.J., Jin, H.G., Kim, H.Y., Ahn, Y.M., Kim, Y.C., Lee, H.S., Lee, Y.J., and Kang, D.G. (2019). Dianthus superbus Improves Glomerular Fibrosis and Renal Dysfunction in Diabetic Nephropathy Model. Nutrients, 11.","DOI":"10.3390\/nu11030553"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S64","DOI":"10.1046\/j.1523-1755.64.s86.12.x","article-title":"Renin\u2013angiotensin system activation and interstitial inflammation in human diabetic nephropathy","volume":"86","author":"Mezzano","year":"2003","journal-title":"Kidney Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1042\/CS20080394","article-title":"Pathogenic perspectives for the role of inflammation in diabetic nephropathy","volume":"116","author":"Rivero","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"F1141","DOI":"10.1152\/ajprenal.00288.2005","article-title":"Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-\u03baB activation","volume":"292","author":"Ohga","year":"2007","journal-title":"Am. J. Physiol. Ren. Physiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/19\/7003\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:12:51Z","timestamp":1760177571000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/19\/7003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,23]]},"references-count":42,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["ijms21197003"],"URL":"https:\/\/doi.org\/10.3390\/ijms21197003","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,23]]}}}