{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:54:23Z","timestamp":1792065263510,"version":"4.4.0"},"reference-count":37,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T00:00:00Z","timestamp":1558396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the PUMC Youth Fund","award":["No. 2017350013"],"award-info":[{"award-number":["No. 2017350013"]}]},{"DOI":"10.13039\/100007471","name":"Applied Basic Research Foundation of Yunnan Province","doi-asserted-by":"publisher","award":["2016FB143"],"award-info":[{"award-number":["2016FB143"]}],"id":[{"id":"10.13039\/100007471","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Technology Innovation Talents Project of Yunnan Province","award":["2017HB097"],"award-info":[{"award-number":["2017HB097"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Obcordata A (OA) is a polyoxypregnane glycoside derived from the Dai medicine Aspidopterys obcordata vines. This study aims to investigate the efficacy of OA on renal tubular epithelial cells exposed to calcium oxalate crystals. We incubated renal tubular cells with 28 \u03bcg\u00b7cm2 calcium oxalate crystals for 24 h with and without OA, GKT137831, phorbol-12-myristate-13-acetate (PMA), and tocopherol. The MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, microscopic examination, flow cytometry, and immunofluorescence staining revealed that calcium oxalate crystals decreased cell viability and elevated reactive oxygen species (ROS) levels. OA, GKT137831, and tocopherol protected cells and decreased ROS levels. However, OA did not exhibit direct DPPH scavenging ability. In addition, immunoblotting illustrated that OA inhibited the NOX4 (nicotinamide adenine dinucleotide phosphate oxidases 4) expression and downregulated the protein expression in the NOX4\/ROS\/p38 MAPK (p38 mitogen-activated protein kinase) pathway. The findings suggest that the cytoprotective and antioxidant effects of OA can be blocked by the NOX4 agonist PMA. In conclusion, OA could be used as a NOX4 inhibitor to prevent kidney stones.<\/jats:p>","DOI":"10.3390\/molecules24101957","type":"journal-article","created":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T10:52:51Z","timestamp":1558435971000},"page":"1957","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy of Obcordata A from Aspidopterys obcordata on Kidney Stones by Inhibiting NOX4 Expression"],"prefix":"10.3390","volume":"24","author":[{"given":"Yihang","family":"Li","sequence":"first","affiliation":[{"name":"Yunnan Branch, Institute of Medicinal Plant, Chinese Academy of Medical Sciences, Peking Union Medical College, Jinghong 666100, China"},{"name":"Key Laboratory of Dai and Southern Medicine of Xishuangbanna Dai Autonomous Prefecture, Jinghong 666100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxu","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana","family":"Lv","sequence":"additional","affiliation":[{"name":"Yunnan Branch, Institute of Medicinal Plant, Chinese Academy of Medical Sciences, Peking Union Medical College, Jinghong 666100, China"},{"name":"Key Laboratory of Dai and Southern Medicine of Xishuangbanna Dai Autonomous Prefecture, Jinghong 666100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Su","sequence":"additional","affiliation":[{"name":"Yunnan Branch, Institute of Medicinal Plant, Chinese Academy of Medical Sciences, Peking Union Medical College, Jinghong 666100, China"},{"name":"Key Laboratory of Dai and Southern Medicine of Xishuangbanna Dai Autonomous Prefecture, Jinghong 666100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2393-5269","authenticated-orcid":false,"given":"Guang","family":"Li","sequence":"additional","affiliation":[{"name":"Yunnan Branch, Institute of Medicinal Plant, Chinese Academy of Medical Sciences, Peking Union Medical College, Jinghong 666100, China"},{"name":"Key Laboratory of Dai and Southern Medicine of Xishuangbanna Dai Autonomous Prefecture, Jinghong 666100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7635-0451","authenticated-orcid":false,"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Yunnan Branch, Institute of Medicinal Plant, Chinese Academy of Medical Sciences, Peking Union Medical College, Jinghong 666100, China"},{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41630","DOI":"10.1038\/srep41630","article-title":"Prevalence of kidney stones in mainland China: A systematic review","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_2","first-page":"8","article-title":"Nephrolithiasis","volume":"6","author":"Januchowski","year":"2014","journal-title":"Osteopath. Fam. Physician"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1007\/s00345-017-2008-6","article-title":"Epidemiology of stone disease across the world","volume":"35","author":"Sorokin","year":"2017","journal-title":"World J. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1001\/jamapediatrics.2015.1419","article-title":"Current Trends, Evaluation, and Management of Pediatric Nephrolithiasis","volume":"169","author":"Hernandez","year":"2015","journal-title":"JAMA Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/ng1762","article-title":"Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6","volume":"38","author":"Jiang","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1080\/00365590600589898","article-title":"Epidemiology of kidney stones in Iceland A population-based study","volume":"40","author":"Indridason","year":"2006","journal-title":"Scand. J. Urol. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00240-005-0463-9","article-title":"International comparison of cost effectiveness of medical management strategies for nephrolithiasis","volume":"33","author":"Lotan","year":"2005","journal-title":"Urol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/sj.ki.5002699","article-title":"Effect of bolus and divided feeding on urine ions and supersaturation in genetic hypercalciuric stone-forming rats","volume":"73","author":"Bushinsky","year":"2008","journal-title":"Kidney Int."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dhayat, N.A., Faller, N., Bonny, O., Mohebbi, N., Ritter, A., Pellegrini, L., Bedino, G., Sch\u00f6nholzer, C., Venzin, R.M., and H\u00fcsler, C. (2018). Efficacy of standard and low dose hydrochlorothiazide in the recurrence prevention of calcium nephrolithiasis (NOSTONE trial): Protocol for a randomized double-blind placebo-controlled trial. BMC Nephrol., 19.","DOI":"10.1186\/s12882-018-1144-6"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s00240-011-0448-9","article-title":"Is oxidative stress, a link between nephrolithiasis and obesity, hypertension, diabetes, chronic kidney disease, metabolic syndrome?","volume":"40","author":"Khan","year":"2012","journal-title":"Urol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"36845","DOI":"10.1074\/jbc.M200832200","article-title":"COM Crystals Activate the p38 Mitogen-activated Protein Kinase Signal Transduction Pathway in Renal Epithelial Cells","volume":"277","author":"Koul","year":"2002","journal-title":"J. Boil. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1093\/ndt\/gfr035","article-title":"Effect of NADPH oxidase inhibition on the expression of kidney injury molecule and calcium oxalate crystal deposition in hydroxy-l-proline-induced hyperoxaluria in the male Sprague\u2013Dawley rats","volume":"26","author":"Zuo","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/1271864","article-title":"Losartan Ameliorates Calcium Oxalate-Induced Elevation of Stone-Related Proteins in Renal Tubular Cells by Inhibiting NADPH Oxidase and Oxidative Stress","volume":"2018","author":"Qin","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0254-6272(16)30052-8","article-title":"Acute toxicity study of Aspidopterys obcordata aqueous extract in Sprague-Dawley rats","volume":"36","author":"Yihang","year":"2016","journal-title":"J. Tradit. Chin. Med."},{"key":"ref_15","first-page":"1047","article-title":"Inhibiting effect of Aspidopterys obcordata Hemsl on renal calculus","volume":"24","author":"Song","year":"2015","journal-title":"Chin. J. New Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.fitote.2018.07.003","article-title":"New polyoxypregnane glycosides from Aspidopterys obcordata vines with antitumor activity","volume":"129","author":"Hu","year":"2018","journal-title":"Fitoterapia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1089\/end.2005.19.759","article-title":"Nonsurgical Management of Urolithiasis: An Overview of Expulsive Therapy","volume":"19","author":"Healy","year":"2005","journal-title":"J. Endourol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/3068365","article-title":"Kidney Stone Disease: An Update on Current Concepts","volume":"2018","author":"Alelign","year":"2018","journal-title":"Adv. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/MEJ.0000000000000324","article-title":"Renal colic: Current protocols for emergency presentations","volume":"23","author":"Leveridge","year":"2016","journal-title":"Eur. J. Emerg. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45766","DOI":"10.1038\/srep45766","article-title":"Association Study of Reported Significant Loci at 5q35.3, 7p14.3, 13q14.1 and 16p12.3 with Urolithiasis in Chinese Han Ethnicity","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1126\/science.1191968","article-title":"Crystal Growth Inhibitors for the Prevention of L-Cystine Kidney Stones through Molecular Design","volume":"330","author":"Rimer","year":"2010","journal-title":"Science"},{"key":"ref_22","first-page":"256","article-title":"Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis","volume":"3","author":"Khan","year":"2014","journal-title":"Transl. Androl. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1442-2042.2007.01953.x","article-title":"Mechanism of calcium oxalate renal stone formation and renal tubular cell injury","volume":"15","author":"Tsujihata","year":"2008","journal-title":"Int. J. Urol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1007\/s002040000173","article-title":"Cultures of exfoliated epithelial cells from different locations of the human urinary tract and the renal tubular system","volume":"74","author":"Golka","year":"2000","journal-title":"Arch. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1248\/bpb.35.539","article-title":"Gallotannin Suppresses Calcium Oxalate Crystal Binding and Oxalate-Induced Oxidative Stress in Renal Epithelial Cells","volume":"35","author":"Lee","year":"2012","journal-title":"Boil. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1248\/cpb.55.1397","article-title":"Cholinesterase Inhibiting and Antiplasmodial Steroidal Alkaloids from Sarcococca hookeriana","volume":"55","author":"Devkota","year":"2007","journal-title":"Chem. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhao, H.-Y., Shao, C.-L., Li, Z.-Y., Han, L., Cao, F., and Wang, C.-Y. (2013). Bioactive Pregnane Steroids from a South China Sea Gorgonian Carijoa sp.. Molecules, 18.","DOI":"10.3390\/molecules18033458"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1210\/me.2005-0156","article-title":"The Nuclear Xenobiotic Receptor Pregnane X Receptor: Recent Insights and New Challenges","volume":"19","author":"Orans","year":"2005","journal-title":"Mol. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1007\/s12272-015-0653-0","article-title":"Nizwaside: A new anticancer pregnane glycoside from the sap of Desmidorchis flava","volume":"38","author":"Hussain","year":"2015","journal-title":"Arch. Pharmacal"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2013","DOI":"10.1038\/cddis.2015.359","article-title":"New view in cell death mode: Effect of crystal size in renal epithelial cells","volume":"6","author":"Sun","year":"2015","journal-title":"Cell Death"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1038\/cdd.2012.18","article-title":"Inhibition of Drp1 provides neuroprotection in vitro and in vivo","volume":"19","author":"Grohm","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13871","DOI":"10.1039\/C8RA02554A","article-title":"Notoginsenoside R1 prevents H9c2 cardiomyocytes apoptosis against hypoxia\/reoxygenation via the ERs\/PI3K\/Akt pathway","volume":"8","author":"Li","year":"2018","journal-title":"RSC Adv."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1046\/j.1523-1755.2003.00866.x","article-title":"Crystal attachment to injured renal collecting duct cells: Influence of urine proteins and pH","volume":"63","author":"Wiessner","year":"2003","journal-title":"Kidney Int."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Jeong, B.Y., Lee, H.Y., Park, C.G., Kang, J., Yu, S.L., Choi, D., Han, S.Y., Park, M.H., Cho, S., and Lee, S.Y. (2018). Oxidative stress caused by activation of NADPH oxidase 4 promotes contrast-induced acute kidney injury. PLoS ONE, 2018.","DOI":"10.1371\/journal.pone.0191034"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1128\/MCB.01393-09","article-title":"Structural Insights into Nox4 and Nox2: Motifs Involved in Function and Cellular Localization","volume":"30","author":"Noack","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1042\/BJ20061903","article-title":"NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation","volume":"406","author":"Serrander","year":"2007","journal-title":"Biochem. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.talanta.2006.03.050","article-title":"Radical scavenging ability of polyphenolic compounds towards DPPH free radical","volume":"71","author":"Troncoso","year":"2007","journal-title":"Talanta"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/10\/1957\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:54:01Z","timestamp":1760187241000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/10\/1957"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,21]]},"references-count":37,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["molecules24101957"],"URL":"https:\/\/doi.org\/10.3390\/molecules24101957","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,21]]}}}