Effects of Monascin on Anti-inflammation Mediated by Nrf2 Activation in Advanced Glycation End Product-Treated THP‑1 Monocytes and Methylglyoxal-Treated Wistar Rats

• Published in: Journal of agricultural and food chemistry Vol. 61; no. 6; pp. 1288 - 1298
• Main Authors: Lee, Bao-Hong, Hsu, Wei-Hsuan, Huang, Tao, Chang, Yu-Ying, Hsu, Ya-Wen, Pan, Tzu-Ming
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 13.02.2013
• Subjects: Animals; Anti-Inflammatory Agents - administration & dosage; antioxidant activity; Cell Line; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - immunology; glycation; Glycation End Products, Advanced - immunology; heme oxygenase (decyclizing); Heterocyclic Compounds, 3-Ring - administration & dosage; Humans; hyperglycemia; inflammation; Male; monocytes; Monocytes - drug effects; Monocytes - immunology; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - immunology; noninsulin-dependent diabetes mellitus; Pyruvaldehyde - immunology; Rats; Rats, Wistar; retinoic acid; silymarin; tumor necrosis factor-alpha; Up-Regulation; methylglyoxal; silymarin; nuclear factor-erythroid 2-related factor-2; receptor for advanced glycation end product; monascin; retinoic acid receptor-α
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf305067n

Hyperglycemia is associated with advanced glycation end products (AGEs). This study was designed to evaluate the inhibitory effects of monascin on receptor for advanced glycation end product (RAGE) signal and THP-1 monocyte inflammation after treatment with S100b, a specific ligand of RAGE. Monascin inhibited cytokine production by S100b-treated THP-1 monocytes via up-regulation of nuclear factor-erythroid 2-related factor-2 (Nrf2) and alleviated p47phox translocation to the membrane. Methylglyoxal (MG, 600 mg/kg bw) was used to induce diabetes in Wistar rats. Inhibitions of RAGE and p47phox by monascin were confirmed by peripheral blood mononuclear cells (PBMCs) of MG-induced rats. Silymarin (SM) was used as a positive control group. It was found that monascin promoted heme oxygenase-1 (HO-1) expression mediated by Nrf2. Suppressions of AGEs, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-β) in serum of MG-induced rats were attenuated in the monascin administration group treated with retinoic acid (RA). RA treatment resulted in Nrf2 inactivation by increasing RA receptor-α (RARα) activity, suggesting that RA acts as an inhibitor of Nrf2. The results showed that monascin exerted anti-inflammatory and antioxidative effects mediated by Nrf2 to prevent the development of diseases such as type 2 diabetes caused by inflammation.