Anthocyanins downregulate lipopolysaccharide-induced inflammatory responses in BV2 microglial cells by suppressing the NF-κB and Akt/MAPKs signaling pathways.

Yung Hyun Choi,Byung Tae Choi,Jin-Woo Jeong,Sung Chul Shin,Gi-Young Kim,Byung Choi,Won Sup Lee

doi:10.3390/ijms14011502

Abstract

Anthocyanins are naturally occurring polyphenols that impart bright color to fruits, vegetables and plants and have a variety of protective properties, which have generally been attributed to their antioxidant capacity. However, little is known about the molecular mechanisms underlying anti-inflammatory effects of anthocyanins related to neurodegenerative diseases. Therefore, we determined whether anthocyanins isolated from black soybean seed coats would inhibit pro-inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated murine BV2 microglial cells. Our results showed that anthocyanins significantly inhibited LPS-induced pro-inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2, and pro-inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, without significant cytotoxicity. Anthocyanins also downregulated excessive expression of inducible NO synthase, cyclooxygenase-2, TNF-α, and IL-1β in LPS-stimulated BV2 cells. Moreover, anthocyanins inhibited nuclear translocation of nuclear factor-kappa B (NF-κB) by reducing inhibitor of NF-κB alpha degradation as well as phosphorylating extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and Akt. These findings suggest that anthocyanins may offer substantial therapeutic potential for treating inflammatory and neurodegenerative diseases accompanied by microglial activation.

Highlights

Microglia are resident macrophages in the central nervous system (CNS) and are thought to be a key mediator of brain disease and injury
The MTT assay was performed at 24 h after treatment with the indicated concentrations of anthocyanins in the presence or absence of LPS to determine the effect of anthocyanins on BV2 cell viability
Activation of NF-κB is closely related to regulation of inducible NO synthase (iNOS), COX-2, tumor necrosis factor-α (TNF-α), and IL-1β genes in activated BV2 cells; we investigated whether anthocyanins modulate the NF-κB

Summary

Introduction

Microglia are resident macrophages in the central nervous system (CNS) and are thought to be a key mediator of brain disease and injury. Microglia become readily activated in response to injury, infection, or inflammation and are capable of producing a variety of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2) and reactive oxygen species, pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α), and potentially neurotoxic compounds [2,3]. These factors are thought to be responsible for some of the deleterious effects of brain injuries and diseases, including ischemia, septic shock, Alzheimer’s disease, Parkinson’s disease, atherosclerosis, multiple sclerosis, and neural death [4,5]. Few studies have been conducted on the effects of anthocyanins on microglia activation related to neurodegenerative disorders

Results

Discussion

Conclusion