Abstract

Aged garlic extract (AGE) is widely used as a dietary supplement on account of its protective effects against oxidative stress and inflammation. But less is known about specific molecular targets of AGE and its bioactive components, including N-α-(1-deoxy-D-fructos-1-yl)-L-arginine (FruArg). Our recent study showed that both AGE and FruArg significantly attenuate lipopolysaccharide (LPS)-induced neuroinflammatory responses in BV-2 microglial cells. This study aims to unveil effects of AGE and FruArg on gene expression regulation in LPS stimulated BV-2 cells. Results showed that LPS treatment significantly altered mRNA levels from 2563 genes. AGE reversed 67% of the transcriptome alteration induced by LPS, whereas FruArg accounted for the protective effect by reversing expression levels of 55% of genes altered by LPS. Key pro-inflammatory canonical pathways induced by the LPS stimulation included toll-like receptor signaling, IL-6 signaling, and Nrf2-mediated oxidative stress pathway, along with elevated expression levels of genes, such as Il6, Cd14, Casp3, Nfkb1, Hmox1, and Tnf. These effects could be modulated by treatment with both AGE and FruArg. These findings suggests that AGE and FruArg are capable of alleviating oxidative stress and neuroinflammatory responses stimulated by LPS in BV-2 cells.

Highlights

  • Fructose-amino acids in Aged garlic extract (AGE), and is an Amadori rearrangement product arising from the condensation reaction between free glucose and arginine during early stages of the Maillard reaction, which is responsible for color formation in foods and, to a large extent, antioxidant properties of AGE14–16

  • Our results show that AGE is capable of repressing levels of pro-inflammatory mRNAs in LPS-treated cells and that FruArg is an active functional component in AGE that accounts for the protective effects

  • The global gene expression profile alterations that were created by LPS stimulus was represented by the differentially expressed genes (DEGs) between BV-2 microglial cells treated with 100 ng/mL LPS and control cells

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Summary

Introduction

Fructose-amino acids in AGE, and is an Amadori rearrangement product arising from the condensation reaction between free glucose and arginine during early stages of the Maillard reaction, which is responsible for color formation in foods and, to a large extent, antioxidant properties of AGE14–16. RNA-Seq analysis was conducted to assess global gene expression affected by AGE and FruArg in LPS-induced BV-2 microglial cells. Our results show that AGE is capable of repressing levels of pro-inflammatory mRNAs in LPS-treated cells and that FruArg is an active functional component in AGE that accounts for the protective effects. The present study addresses the regulatory function of AGE and FruArg on LPS-stimulated cells with respect to global gene expression by providing quantitative information about the population of mRNA species. The data broaden our understanding of the effect of AGE and FruArg to the level of gene expression regulation and suggested their therapeutic potential for mitigating inflammatory abnormalities in the aging individuals

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