Ganoderic Acid A Attenuates LPS-Induced Neuroinflammation in BV2 Microglia by Activating Farnesoid X Receptor

Yue Jia,Hongkun Bao,Haoran Li,Jing Du,Hua Yin,Dandan Zhang

doi:10.1007/s11064-021-03303-3

Abstract

Neuroinflammation plays an important role in the onset and progression of neurodegenerative diseases. Microglia-mediated neuroinflammation have been proved to be the main reason for causing the neurodegenerative diseases. Ganoderic acid A (GAA), isolated from Ganoderma lucidum, showed anti-inflammatory effect in metabolism diseases. However, little research has been focused on the effect of GAA in neuroinflammation and the related mechanism. In the present study, lipopolysaccharide(LPS)-stimulated BV2 microglial cells were used to evaluate the anti-inflammatory capacity of GAA. Our data showed that GAA significantly suppressed LPS-induced BV2 microglial cells proliferation and activation in vitro. More strikingly, GAA promoted the conversion of BV2 microglial cells from M1 status induced by LPS to M2 status. Furthermore, GAA inhibited the pro-inflammatory cytokines release and promoted neurotrophic factor BDNF expression in LPS-induced BV2 microglial cells. Finally, we found that the expression of farnesoid-X-receptor (FXR) was prominently downregulated in LPS-stimulated BV2 microglial cells, antagonism of FXR with z-gugglesterone and FXR siRNA can reverse the effect of GAA in LPS-induced BV2 microglial cells. Taking together, our findings demonstrate that GAA can significantly inhibit LPS-induced neuroinflammation in BV2 microglial cells via activating FXR receptor.

Highlights

Neuroinflammation, inflammation of the central nervous system (CNS), is an immune response often initiated against a variety of harmful stimuli, including pathogens, trauma and neural damage, etc
The results showed that Ganoderic acid A (GAA) treatment had no cytotoxicity to BV2 microglial cells at the dosage from 1 to 100 μg/ml, it began to exert cytotoxic effect at the dosage of 200 μg/ml (Fig. 2a)
We evaluated whether GAA can inhibit LPS-induced microglial proliferation, BV2 microglial cells were cultured with different concentrations of GAA and with LPS (0.5 μg/ml) for 24 h

Summary

Introduction

Neuroinflammation, inflammation of the central nervous system (CNS), is an immune response often initiated against a variety of harmful stimuli, including pathogens, trauma and neural damage, etc. The inflammation reaction is an automatic defense response of the body to external stimuli. In some cases, it is usually beneficial because it can promote the clearance of pathogenic factors and the healing of damaged tissue; but in other cases, it is detrimental because it can aggravate the damage of injured tissue or cells and worsen the condition [4]. Microglia are the resident macrophages of the CNS and plays an important role in immune surveillance, homeostasis and neuroinflammation [5].

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