https://scholars.lib.ntu.edu.tw/handle/123456789/377133
標題: | A novel natural Nrf2 activator with PPARγ-agonist (monascin) attenuates the toxicity of methylglyoxal and hyperglycemia | 作者: | TZU-MING PAN | 關鍵字: | Advanced glycation end-products (AGEs); Methylglyoxal (MG); Nuclear factor-erythroid 2-related factor 2 (Nrf2); Peroxisome proliferator-activated receptor-γ (PPARγ) | 公開日期: | 2013 | 卷: | 272 | 期: | 3 | 起(迄)頁: | 842-851 | 來源出版物: | Toxicology and Applied Pharmacology | 摘要: | Methylglyoxal (MG) is a toxic-glucose metabolite and a major precursor of advanced glycation endproducts (AGEs). MG has been reported to result in inflammation by activating receptor for AGEs (RAGE). We recently found that Monascus-fermented metabolite monascin acts as a novel natural peroxisome proliferator-activated receptor-γ (PPARγ) agonist that improves insulin sensitivity. We investigated the metabolic, biochemical, and molecular abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats treated with oral administration of monascin or rosiglitazone. Monascin (a novel PPARγ agonist) activated nuclear factor-erythroid 2-related factor 2 (Nrf2) and down-regulated hyperinsulinmia in oral glucose tolerance test (OGTT). Monascin was able to elevate glyoxalase-1 expression via activation of hepatic Nrf2, hence, resulting in MG metabolism to d-lactic acid and protected from AGEs production in MG-treated rats. Rosiglitazone did not activate Nrf2 nor glyoxalase expression to lower serum and hepatic AGEs levels. Monascin acts as a novel natural Nrf2 activator with PPARγ-agonist activity were confirmed by Nrf2 and PPARγ reporter assays in Hep G2 cells. These findings suggest that monascin acts as an anti-diabetic and anti-oxidative stress agent to a greater degree than rosiglitazone and thus may have therapeutic potential for the prevention of diabetes. ? 2013 Elsevier Inc. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84884676723&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/377133 |
DOI: | 10.1016/j.taap.2013.07.004 | SDG/關鍵字: | advanced glycation end product receptor; glucose; glyoxalase; insulin; interleukin 1beta; lactic acid; methylglyoxal; monascin; peroxisome proliferator activated receptor gamma; peroxisome proliferator activated receptor gamma agonist; rosiglitazone; small interfering RNA; transcription factor Nrf2; tumor necrosis factor alpha; unclassified drug; animal experiment; antidiabetic activity; antioxidant activity; article; cell strain HepG2; controlled study; enzyme linked immunosorbent assay; glucose blood level; hyperglycemia; hyperinsulinemia; immunohistochemistry; insulin blood level; insulin sensitivity; insulin tolerance test; male; nonhuman; oral glucose tolerance test; protein expression; rat; Advanced glycation end-products (AGEs); Methylglyoxal (MG); Nuclear factor-erythroid 2-related factor 2 (Nrf2); Peroxisome proliferator-activated receptor-γ (PPARγ); Animals; Dose-Response Relationship, Drug; Hep G2 Cells; Heterocyclic Compounds, 3-Ring; Humans; Hyperglycemia; Male; NF-E2-Related Factor 2; PPAR gamma; Pyruvaldehyde; Rats; Rats, Wistar |
顯示於: | 生化科技學系 |
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