{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:47:02Z","timestamp":1789991222014,"version":"4.0.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>NAD(P)H oxidase contributes to the pathogenesis of cancer and cardiovascular diseases such as hypertension, atherosclerosis, restenosis, cardiac hypertrophy and heart failure. Plumbagin, a plant-derived naphthoquinone, has been shown to exert anticarcinogenic and anti-atherosclerosis effects in animals. However, the molecular mechanisms underlying these effects remain unknown. It is possible that the beneficial effect of plumbagin is due to the inhibition of NAD(P)H oxidase. Human embryonic kidney 293 (HEK293) and brain tumour LN229 cells express mainly Nox-4, a renal NAD(P)H oxidase. We have examined the effect of plumbagin on Nox-4 activity in HEK293 and LN229 cells using lucigenin-dependent chemiluminescence assay. Plumbagin inhibited the activity of Nox-4 in a time- and dose-dependent manner in HEK293 and LN229 cells. Production of superoxide in HEK293 cells was inhibited by diphenyleneiodonium (DPI), a NAD(P)H oxidase inhibitor. The superoxide production in HEK293 cells was NADPH- and NADH-dependent indicating that the superoxide was generated by a NAD(P)H oxidase in HEK293 cells, but not by the redox-cycling of lucigenin. Furthermore, plumbagin inhibited the superoxide production in Nox-4 transfected COS-7 cells. These results indicated that plumbagin directly interacted with Nox-4 and inhibited its activity.<\/jats:p>","DOI":"10.1211\/0022357055119","type":"journal-article","created":{"date-parts":[[2004,12,15]],"date-time":"2004-12-15T00:16:47Z","timestamp":1103069807000},"page":"111-116","source":"Crossref","is-referenced-by-count":114,"title":["Inhibition of Nox-4 activity by plumbagin, a plant-derived bioactive naphthoquinone"],"prefix":"10.1093","volume":"57","author":[{"given":"Yaxian","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Medicine, Case Western Reserve University and University Hospital of Cleveland , Cleveland, Ohio 44106,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Jiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Case Western Reserve University and University Hospital of Cleveland , Cleveland, Ohio 44106,","place":["USA"]},{"name":"Department of Medicine, Reproductive Research Center, Shandong Provincial Hospital, Shandong University , Jinan,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiguo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Case Western Reserve University and University Hospital of Cleveland , Cleveland, Ohio 44106,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danian","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Medicine, Case Western Reserve University and University Hospital of Cleveland , Cleveland, Ohio 44106,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Vetter","sequence":"additional","affiliation":[{"name":"Department of Medicine, Case Western Reserve University and University Hospital of Cleveland , Cleveland, Ohio 44106,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Ho","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Case Western Reserve University and University Hospital of Cleveland , Cleveland, Ohio 44106,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,1,1]]},"reference":[{"key":"2024103109413243900_cit1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1161\/01.HYP.25.2.155","article-title":"Hypertension and the pathogenesis of atherosclerosis: oxidative stress and the mediation of arterial inflammatory response \u2014 a new perspective","volume":"25","author":"Alexander","year":"1995","journal-title":"Hypertension"},{"key":"2024103109413243900_cit2","doi-asserted-by":"crossref","first-page":"7915","DOI":"10.1073\/pnas.90.17.7915","article-title":"Oxidants, antioxidants, and the degenerative diseases of aging","volume":"90","author":"Ames","year":"1993","journal-title":"Proc. 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