A novel natural Nrf2 activator with PPARγ-agonist (monascin) attenuates the toxicity of methylglyoxal and hyperglycemia
Journal
Toxicology and Applied Pharmacology
Journal Volume
272
Journal Issue
3
Pages
842-851
Date Issued
2013
Author(s)
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. ? 2013 Elsevier Inc.
Subjects
Advanced glycation end-products (AGEs); Methylglyoxal (MG); Nuclear factor-erythroid 2-related factor 2 (Nrf2); Peroxisome proliferator-activated receptor-γ (PPARγ)
SDGs
Other Subjects
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
Type
journal article