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: Wei-Hsuan Hsu, Bao-Hong Lee, Yu-Ying Chang, Ya-Wen Hsu, Tzu-Ming Pan
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 272 Issue 3 Pg. 842-51 (Nov 01 2013) ISSN: 1096-0333 [Electronic] United States
• PMID: 23954466 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Heterocyclic Compounds, 3-Ring
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• PPAR gamma
• Pyruvaldehyde
• monascin

Topics

• Animals
• Dose-Response Relationship, Drug
• Hep G2 Cells
• Heterocyclic Compounds, 3-Ring (pharmacology, therapeutic use)
• Humans
• Hyperglycemia (metabolism, prevention & control)
• Male
• NF-E2-Related Factor 2 (metabolism)
• PPAR gamma (agonists, metabolism)
• Pyruvaldehyde (antagonists & inhibitors, toxicity)
• Rats
• Rats, Wistar