A novel natural Nrf2 activator with PPAR gamma-agonist (monascin) attenuates the toxicity of methylglyoxal and hyperglycemia

作者：Hsu Wei Hsuan; Lee Bao Hong; Chang Yu Ying; Hsu Ya Wen; Pan Tzu Ming^*

来源：Toxicology and Applied Pharmacology, 2013, 272(3): 842-851.

DOI：10.1016/j.taap.2013.07.004

• Methylglyoxal (MG)
• Advanced glycation end-products (AGEs)
• Peroxisome proliferator-activated receptor-gamma (PPAR gamma)
• Nuclear factor-erythroid 2-related factor 2 (Nrf2)

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-gamma (PPAR gamma) 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 PPAR gamma 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 PPAR gamma-agonist activity were confirmed by Nrf2 and PPAR gamma 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.

• 出版日期2013-11-1