Monascin Attenuates Oxidative Stress-Mediated Lung Inflammation via Peroxisome Proliferator-Activated Receptor-Gamma (PPAR-γ) and Nuclear Factor-Erythroid 2 Related Factor 2 (Nrf-2) Modulation

Abstract

We speculated that peroxisome proliferator-activated receptor (PPAR)-γ agonists may modulate the oxidative stress pathway to ameliorate the development of airway inflammation. The effect of Monascus-fermented metabolite monascin (MS) and rosiglitazone (Rosi) on oxidative stress-induced lung inflammation was evaluated. Luciferase assay and DNA binding activity assay were used to point out that MS may be a novel PPAR-γ agonist and nuclear factor-erythroid 2 related factor 2 (Nrf-2) activator. We used hydrogen peroxide (H2O2) to induce inflammation in lung epithelial cells. MS and Rosi prevented H2O2-induced ROS generation in A549 epithelial cells through PPAR-γ translocation, avoiding inflammatory mediator expression via inhibiting nuclear factor (NF)-κB translocation. The regulatory ability of MS was abolished by siRNA against PPAR-γ. MS also elevated antioxidant enzyme expression via Nrf-2 activation. Both PPAR-γ and Nrf-2 might have benefits against lung inflammation. MS regulated PPAR-γ and Nrf-2 to improve lung oxidative inflammation.

Effect of long-term maternal smoking on the offspring’s lung health

“…Mitochondria are the major cellular source of ROS (59) and as such are a pharmacological target for ROS production. It is well established that oxidative stress can induce the secretion of inflammatory cytokines and the expression of adhesion molecules and inflammatory mediators in the lung (3,24,27). It has also been shown that maternal smoking can significantly increase oxidative stress in the offspring, including the lung tissue (4).…”

Monascus Secondary Metabolites Monascin and Ankaflavin Inhibit Activation of RBL-2H3 Cells

“…As shown in Figure 5, monascin and ankaflavin influenced the previous work, monascin and ankaflavin improved the ovalbumin-induced BALB/c airway allergic inflammation. 10,16 Monascin also down-regulated the maturation of dendritic cells and Th2 cytokine production. 16 We suggest that monascin and ankaflavin could suppress allergic reaction.…”

“…10,16 Monascin also down-regulated the maturation of dendritic cells and Th2 cytokine production. 16 We suggest that monascin and ankaflavin could suppress allergic reaction. To sum up these observations, monascin and ankaflavin may have a relieving effect on type I allergy patients and thus have potential for development into medicine s such as azelastine.…”

“…Monascin, ankaflavin, and rosiglitazone are PPARγ ligands. 16 In addition, many PPARγ agonists have been proven to possess an improving effect on the activation of mast cells. 18 To verify whether the ameliorative expressions of monascin, ankaflavin, and rosiglitazone on activation are achieved by PPARγ activation, we added the PPARγ antagonist GW9662 with samples to the cells for 24 h, and then we stimulated cells with PMA/ionomycin.…”

“…14,15 Additionally, monascin and ankaflavin have been proven to improved ovalbumin-treated BALB/c mice airway inflammation, which is a commonly used model of asthma. 10,16 Our previous study further examined whether monascin and ankaflavin affect participative cells in allergy. We found that monascin inhibited the maturation of dendritic cells, which belong to APCs.…”