Platycodin D Inhibits Inflammatory Response in LPS-Stimulated Primary Rat Microglia Cells through Activating LXRα-ABCA1 Signaling Pathway.

Yunhe Fu,Jiaxin Wang,Yanan Wang,Jingjing Wang,Bin Liu,Zhuoyuan Xin,Xu Zhang,Fan Li

doi:10.3389/fimmu.2017.01929

Yunhe Fu, Jiaxin Wang + Show 6 more

Open Access

https://doi.org/10.3389/fimmu.2017.01929

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Abstract

Platycodin D (PLD), an effective triterpenesaponin extracted from Platycodon grandiflorum, has been known to have anti-inflammatory effect. In the present study, we investigate the anti-inflammatory effects of PLD on LPS-induced inflammation in primary rat microglia cells. The results showed that PLD significantly inhibited LPS-induced ROS, TNF-α, IL-6, and IL-1β production in primary rat microglia cells. PLD also inhibited LPS-induced NF-κB activation. Furthermore, our results showed that PLD prevented LPS-induced TLR4 translocation into lipid rafts via disrupting the formation of lipid rafts by inducing cholesterol efflux. In addition, PLD could activate LXRα–ABCA1 signaling pathway which induces cholesterol efflux from cells. The inhibition of inflammatory cytokines by PLD could be reversed by SiRNA of LXRα. In conclusion, these results indicated that PLD prevented LPS-induced inflammation by activating LXRα–ABCA1 signaling pathway, which disrupted lipid rafts and prevented TLR4 translocation into lipid rafts, thereby inhibiting LPS-induced inflammatory response.

Highlights

Neuroinflammation plays a critical role in the pathogenesis of neurodegenerative diseases [1, 2]
The results showed that LPS significantly upregulated the levels of ROS, TNF-α, IL-1β, and IL-6 in primary rat microglia cells
Our results showed that the inhibition of Platycodin D (PLD) on TNF-α, IL-1β, and IL-6 production were reversed by LXRα antagonist geranylgeranyl pyrophosphate (Figure 6)

Summary

Introduction

Neuroinflammation plays a critical role in the pathogenesis of neurodegenerative diseases [1, 2]. LPS leads to the activation of TLR4 signaling pathway, as well as the activation of NF-κB and inflammatory cytokines release in microglia [6]. Overproduction of these cytokines leads to the pathogenesis of neurodegenerative diseases [7]. Inhibition of these inflammatory cytokines may attenuate the development of neurodegenerative diseases. Disruption of lipid rafts could inhibit TLR4 signaling pathway through preventing TLR4 translocation into lipid rafts

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