Synergistic Regulation of Microglia Gene Expression by Natural Molecules in Herbal Medicine

Qiburi Qiburi,Temuqile Temuqile,Huricha Baigude

doi:10.1155/2021/9920364

Abstract

The activated microglia contribute to stroke-induced neuroinflammation by upregulating the expression of a pleura of genes that are characterized as either proinflammatory or anti-inflammatory. The natural products alantolactone (Ala) and dehydrodiisoeugenol (Deh) found in Inula helenium L. and Myristica fragrans Houtt., respectively, are regularly used in traditional herb medicine, which play anti-inflammatory and antioxidant roles via regulation of canonical pathways such as nuclear factor kappa B (NF-κB) in microglia and microphages. To illustrate the full spectra of gene expression alteration in microglia treated with Ala, Deh, and the mixture of Ala and Deh (denoted as Mix), we performed RNA-seq analysis of total RNA extracted from lipopolysaccharide- (LPS-) treated microglia subsequently exposed to Ala, Deh, and Mix. While both chemicals regulated the gene expression that facilitates an anti-inflammatory polarization, the mixture exerted some distinctive synergic regulatory effect, which differed from either of the chemicals alone. Our data provide important evidence for further research on the therapeutic mechanism of traditional medicine including Eerdun Wurile (EW).

Highlights

Microglia are the main immune cells in the central nervous system (CNS) [1, 2]
Various reports suggest that the modulation of microglia-derived cytokines and neuroinflammatory proteins may play a neuroprotective role in brain injury [8,9,10,11]
To obtain the optimal concentration of the compounds for further in vitro assay, the MTS assay was performed in this experiment. e results showed that Ala and Deh did not impact the BV2 cells viability at concentrations 21.5 μM and 1.0 μM, respectively (P < 0.05) (Figure 1). erefore, the concentrations of 21.5 μM Ala and 1.0 μM Deh were used for the following experiment

Summary

Introduction

Microglia are the main immune cells in the central nervous system (CNS) [1, 2]. In a normal brain, resting microglia exhibit a ramified phenotype and play an important role in monitoring the brain parenchyma and interacting dynamically with neighboring neurons, astrocytes, and blood vessels [3, 4]. In the middle cerebral artery occlusion and reperfusion (MCAO/R) rat model, Ala could inhibit the expression of proinflammatory factors via suppression of NF-κB and MAPK signaling pathways [17] and had neuroprotective effect in traumatic brain injured rats [16]. We hypothesize that the neuroprotective effect of EW results from the synergic effect of active chemicals including Ala and Deh. To assess the combinatory effect of Ala and Deh on microglia polarization, in this report, we investigated the impact of each single molecule as well as the mixture on the gene expression pattern of BV2 cells, focusing on the inflammation pathways. We used RNA-seq technology to confirm the synergistic regulation of gene expression in LPSstimulated microglia by natural products, Ala and Deh. Significant differential expression was discovered in the synergistic effect of the two bioactive molecules, including anti-inflammatory and antioxidant effects, which may provide the neuroprotective mechanism of EW

Materials and Methods

Results

Discussion