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

Abstract

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.

Compounds Blocking Methylglyoxal-induced Protein Modification and Brain Endothelial Injury

“…These antioxidant and antiglycation properties may explain the efficacy of retinoic acid against MG toxicity on brain endothelial cells according to real-time viability assay. The beneficial effect of retinoic acid was also reported in MG-induced diabetes in rats (63). In the present study retinoic acid preserved the integrity of the endothelial barrier from the permeability increasing effect of MG.…”

Resveratrol Protects against Methylglyoxal-Induced Hyperglycemia and Pancreatic Damage In Vivo

“…In agreement with these previous studies, our study indicated that resveratrol can at least partially activate the ERK signaling pathway, which was previously shown to enhance Nrf2 nuclear translocation and activation [ 39 ]. In addition, activation of Nrf2 by several compounds, including monascin, ankaflavin and dimerumic acid, elevated MG metabolism to alleviate diabetic damage in vivo [ 53 , 54 , 55 , 56 ]. Activation of Nrf2 also protected from oxidation of high-density lipoprotein cholesterol [ 57 ] and airway inflammation in vivo [ 58 ].…”

Methylglyoxal in Metabolic Disorders: Facts, Myths, and Promises

“…NAC is a clinically approved drug with antioxidant properties, which is known as an MG scavenger and inhibitor of ROS formation both in vitro and in vivo . Monascin, a novel product derived from the mold gender Monascus with potential antidiabetic properties, was recently identified as an agonist of both Nrf2 and PPARγ, having protective effects on MG‐induced toxicity, anti‐inflammatory properties in MG‐treated monocytes and protecting effects in MG‐treated β‐cells . However, more studies are necessary to evaluate its therapeutic potential.…”