title: A novel natural Nrf2 activator with PPARγ-agonist (monascin) attenuates the toxicity of methylglyoxal and hyperglycemia.
abstract: 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.
authors: Department of Biochemical Science & Technology, College of Life Science, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
authors: Wei-Hsuan
authors: WH
authors: Hsu
authors: Bao-Hong
authors: BH
authors: Lee
authors: Yu-Ying
authors: YY
authors: Chang
authors: Ya-Wen
authors: YW
authors: Hsu
authors: Tzu-Ming
authors: TM
authors: Pan
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D047495:PPAR gamma; D011765:Pyruvaldehyde; C517880:monascin
keywords: Advanced glycation end-products (AGEs); Methylglyoxal (MG); Nuclear factor-erythroid 2-related factor 2 (Nrf2); Peroxisome proliferator-activated receptor-γ (PPARγ)