Inhibitory Effects of Myricetin on Lipopolysaccharide-Induced Neuroinflammation.

Jung-Hee Jang,Kyungsook Jung,Gunhyuk Park,Seung Hoon Lee,Horyong Yoo

doi:10.3390/brainsci10010032

Abstract

Microglial activation elicits an immune response by producing proinflammatory modulators and cytokines that cause neurodegeneration. Therefore, a plausible strategy to prevent neurodegeneration is to inhibit neuroinflammation caused by microglial activation. Myricetin, a natural flavanol, induces neuroprotective effects by inhibiting inflammation and oxidative stress. However, whether myricetin inhibits lipopolysaccharide (LPS)-induced neuroinflammation in hippocampus and cortex regions is not known. To test this, we examined the effects of myricetin on LPS-induced neuroinflammation in a microglial BV2 cell line. We found that myricetin significantly downregulated several markers of the neuroinflammatory response in LPS-induced activated microglia, including inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory modulators and cytokines such as prostaglandin E2 (PGE2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Moreover, myricetin suppressed the expression of c-Jun NH2-terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK), which are components of the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, myricetin inhibited LPS-induced macrophages and microglial activation in the hippocampus and cortex of mice. Based on our results, we suggest that myricetin inhibits neuroinflammation in BV2 microglia by inhibiting the MAPK signaling pathway and the production of proinflammatory modulators and cytokines. Therefore, this could potentially be used for the treatment of neuroinflammatory diseases.

Highlights

Microglia are found in the central nervous system (CNS) where they play a pivotal role in the immune response and maintaining homeostasis in the brain, protecting the CNS against diverse types of pathogens
We found that myricetin prevented LPS-induced neuroinflammation by suppressing proinflammatory cytokines (IL-1β and TNF- α), the overexpression of nitric oxide (NO) and prostaglandin E2 (PGE2), and protein overexpression of inducible nitric oxide (NO) synthase (iNOS) and COX-2, by interfering with mitogen-activated protein kinase (MAPK) signaling pathways
We demonstrated that myricetin remarkably inhibited the generation of tumor necrosis factor-α (TNF-α), IL-1β and PGE2 in LPS-stimulated BV2 microglia

Summary

Introduction

Microglia are found in the central nervous system (CNS) where they play a pivotal role in the immune response and maintaining homeostasis in the brain, protecting the CNS against diverse types of pathogens. Injury and irritants such as lipopolysaccharide (LPS) lead to the activation of microglia and the release of various cytokine and chemokine factors including cyclooxygenase-2 (COX-2). Inducible nitric oxide (NO) synthase (iNOS), inflammatory modulators such as prostaglandin. Brain Sci. 2020, 10, 32; doi:10.3390/brainsci10010032 www.mdpi.com/journal/brainsci. Brain Sci. 2020, 10, 32 factor-α (TNF-α) [1,2,3,4]. These neuroinflammatory molecules secreted by activated microglia are reported to be associated with mitogen-activated protein kinase (MAPK), nuclear factor (NF)-κB signaling [2,5]. Inhibiting neuroinflammatory events in microglia may be a promising strategy for preventing the progression of neuroinflammatory-modulated neurodegenerative diseases

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