Morin hydrate suppresses lipoteichoic acid-induced oxidative stress-mediated inflammatory events in macrophages via augmenting Nrf2/HO-1 and antioxidant defense molecules

Abstract

Oxidative stress induces chronic inflammatory diseases in aerobic organisms, and antioxidants from plants represent an efficient strategy to prevent this condition. Morin hydrate (MH), a bioactive flavonoid, has a wide range of pharmacological properties, including anti-inflammatory and anti-oxidant. This study evaluated the protective effects of MH on lipoteichoic acid (LTA)-induced inflammation in RAW 264.7 macrophages by testing the main oxidative and inflammatory biomarkers and also investigating the molecular pathways involved. The antioxidant and anti-inflammatory effects of MH were evaluated in a cell-free system and RAW264.7 cells. Quantitative real-time PCR (RT-qPCR) and assay kits were used to measure the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) mRNA, as well as the activity of antioxidant enzymes. The effects of MH on LTA-induced inducible nitric oxide synthase (iNOS), IL-1β, and TNF-α mRNA and protein expression were also evaluated by RT-qPCR and Western blotting. MH reduced DPPH and ABTS radicals in a cell-free system and LTA-induced ROS and NO production in RAW264.7 cells. MH upregulated Nrf2 and HO-1 mRNA expression and reversed LTA-mediated reduction of antioxidant enzymes, at a high concentration of 20 µM pretreated cells. MH also effectively attenuated LTA-induced iNOS, IL-1β, and TNF-α mRNA and protein expression, and these effects were reversed by ML385. The study found that the Nrf2/HO-1 played role in the inhibition of LTA-induced oxidative stress in macrophages by MH. This study may consider to be a promising induced macrophage-targeted strategy via regulating anti-oxidative defense to control inflammatory-related disease.