Inhibitory effects on the production of inflammatory mediators and reactive oxygen species by Mori folium in lipopolysaccharide-stimulated macrophages and zebrafish.

Da Hye Kwon,Jin Woo Jeong,Su Hyun Hong,Hye-Jin Hwang,Ki Won Lee,Hye Won Lee,Sung Goo Kim,Chang-Gue Son,Yung Hyun Choi,Eun Ok Choi,Ki Young Kim,Cheol Park,Gi-Young Kim

doi:10.1590/0001-3765201720160836

Abstract

Mori folium, the leaf of Morus alba L. (Moraceae), has been traditionally used for various medicinal purposes from ancient times to the present. In this study, we examined the effects of water extract of Mori folium (WEMF) on the production of inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. Our data indicated that WEMF significantly suppressed the secretion of NO and PGE2 in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects were accompanied by a marked reduction in their regulatory gene expression at the transcription level. WEMF attenuated LPS-induced intracellular ROS production in RAW 264.7 macrophages. It inhibited the nuclear translocation of the nuclear factor-kappa B p65 subunit and the activation of mitogen-activated protein kinases in LPS-treated RAW 264.7 macrophages. Furthermore, WEMF reduced LPS-induced NO production and ROS accumulation in zebrafish. Although more efforts are needed to fully understand the critical role of WEMF in the inhibition of inflammation, the findings of the present study may provide insights into the approaches for Mori folium as a potential therapeutic agent for inflammatory and antioxidant disorders.

Highlights

Inflammation is a primary protective response of the body involving the activation of immune system processes
When macrophages are over-activated by inflammatory stimulants, including the gramnegative bacterial endotoxin lipopolysaccharides (LPS), the cells induce the production of inflammatory mediators, including nitric oxide (NO) and prostaglandin E2 (PGE2), and inflammatory cytokines along with the activation of several signaling pathways, such as nuclear factorkappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling (Kaminska 2005, Lu et al 2011, Rigoglou and Papavassiliou 2013, Muralidharan and Mandrekar 2013)
To exclude the cellular toxicity caused by water extract of Mori folium (WEMF) treatment, RAW 264.7 cells were treated with WEMF and/or LPS for 24 h

Summary

Introduction

Inflammation is a primary protective response of the body involving the activation of immune system processes. When macrophages are over-activated by inflammatory stimulants, including the gramnegative bacterial endotoxin lipopolysaccharides (LPS), the cells induce the production of inflammatory mediators, including nitric oxide (NO) and prostaglandin E2 (PGE2), and inflammatory cytokines along with the activation of several signaling pathways, such as nuclear factorkappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling (Kaminska 2005, Lu et al 2011, Rigoglou and Papavassiliou 2013, Muralidharan and Mandrekar 2013) Excessive production of these inflammatory mediators and cytokines further provoke deleterious consequences in the pathogenesis of many inflammatory diseases (McDaniel et al 1996, Muralidharan and Mandrekar 2013). The overproduced ROS by activated macrophages acts as an important contributor to the manifestation of inflammation (Varga et al 2013, Mills and O'Neill 2016), and it is involved in the production of inflammatory mediators in LPS-

Methods

Results

Discussion

Conclusion