{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:09:50Z","timestamp":1789409390366,"version":"build-2803163510"},"reference-count":86,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,7,24]],"date-time":"2012-07-24T00:00:00Z","timestamp":1343088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND AND PURPOSE<\/jats:bold>\n                    Diabetes is characterized by hyperglycaemia, which facilitates the formation of advanced glycation end\u2010products (AGEs). Type 2 diabetes mellitus is commonly accompanied by non\u2010alcoholic steatohepatitis, which could lead to hepatic fibrosis. Receptor for AGEs (RAGE) mediates effects of AGEs and is associated with increased oxidative stress, cell growth and inflammation. The phytochemical curcumin inhibits the activation of hepatic stellate cells (HSCs), the major effectors during hepatic fibrogenesis. The aim of this study was to explore the underlying mechanisms of curcumin in the elimination of the stimulating effects of AGEs on the activation of HSCs. We hypothesize that curcumin eliminates the effects of AGEs by suppressing gene expression of RAGE.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>\n                    Gene promoter activities were evaluated by transient transfection assays. The expression of\n                    <jats:italic>rage<\/jats:italic>\n                    was silenced by short hairpin RNA. Gene expression was analysed by real\u2010time PCR and Western blots. Oxidative stress was evaluated.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>KEY RESULTS<\/jats:bold>\n                    AGEs induced\n                    <jats:italic>rage<\/jats:italic>\n                    expression in cultured HSCs, which played a critical role in the AGEs\u2010induced activation of HSCs. Curcumin at 20\u2003\u00b5M eliminated the AGE effects, which required the activation of PPAR\u03b3. In addition, curcumin attenuated AGEs\u2010induced oxidative stress in HSCs by elevating the activity of glutamate\u2010cysteine ligase and by stimulating\n                    <jats:italic>de novo<\/jats:italic>\n                    synthesis of glutathione, leading to the suppression of gene expression of RAGE.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION AND IMPLICATIONS<\/jats:bold>\n                    Curcumin suppressed gene expression of RAGE by elevating the activity of PPAR\u03b3 and attenuating oxidative stress, leading to the elimination of the AGE effects on the activation of HSCs.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>LINKED ARTICLE<\/jats:bold>\n                    This article is commented on by Stefanska, pp. 2209\u20132211 of this issue. To view this commentary visit\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/j.1476-5381.2012.01959.x\">http:\/\/dx.doi.org\/10.1111\/j.1476\u20105381.2012.01959.x<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1111\/j.1476-5381.2012.01910.x","type":"journal-article","created":{"date-parts":[[2012,2,21]],"date-time":"2012-02-21T12:28:13Z","timestamp":1329827293000},"page":"2212-2227","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Curcumin inhibits gene expression of receptor for advanced glycation end\u2010products (RAGE) in hepatic stellate cells\n                    <i>in vitro<\/i>\n                    by elevating PPAR\u03b3 activity and attenuating oxidative 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