Hydroxysafflor Yellow A Exerts Anti-Inflammatory Effects Mediated by SIRT1 in Lipopolysaccharide-Induced Microglia Activation.

Xiude Qin,Haobin Cai,Chuanpeng Li,Jinfang Li,Juanjuan Chen,Haotao Zheng,Tianxiang Guan,Hong Xue,Guowei Zhang,Jinqiang Zhu,Yu Liu

doi:10.3389/fphar.2020.01315

Abstract

Abnormal microglia activation causes sever neuroinflammation, contributing to the development of many diseases, yet the mechanism remains incompletely unknown. In current study, we identified that Hydroxysafflor yellow A (HYA), a chalcone glycoside derived from Carthamus tinctorius L effectively attenuates LPS-induced inflammation response in primary microglia via regulating the expression of inflammatory genes and remodeling the polarization of microglia. We also reported the effects of HYA on improving lipopolysaccharide (LPS)-stimulated mitochondrial dysfunction and oxidative stress for the first time. Interestingly, we found that HYA could serves as an effective SIRT1 activator. Deficiency of SIRT1 abrogates the protective effects of HYA against LPS-induced response. Overall, our data suggest HYA, a novel SIRT1 activator, could serve as an effective approach to treat LPS-induced neurodegenerative diseases.

Highlights

Previous studies indicated that abnormal activation of microglia leads to neuroinflammation and contributes to the development of some several diseases, including Parkinson’s disease, Alzheimer’s disease, and other diseases sclerosis and encephalitis (Nolan et al, 2013; Heppner et al, 2015; Borjini et al, 2016; Schwartz and Deczkowska, 2016)
Hydroxysafflor yellow A (HYA) supplement significantly suppressed the LPS-induced activation of microglia and the secretion of pro-inflammatory cytokines
The anti-inflammatory effects of HYA could be effectively abolished by the SIRT1 antagonist, EX-527, even on LPS-induced state

Summary

Introduction

Previous studies indicated that abnormal activation of microglia leads to neuroinflammation and contributes to the development of some several diseases, including Parkinson’s disease, Alzheimer’s disease, and other diseases sclerosis and encephalitis (Nolan et al, 2013; Heppner et al, 2015; Borjini et al, 2016; Schwartz and Deczkowska, 2016). Neuroinflammation homeostasis is mainly contributed by the microglia cells, which actively survey the brain micro-environment dependent on its activation. The microglias are over-activated and secrets pro-inflammatory cytokines to neighboring neurons, which is considered as a deleterious risk for the microenvironment health (Hirsch and Hunot, 2009). Several studies indicated that genetic or no-genetic factors which inhibits its activation, have been recognized as main approaches to delay or therapy neuroinflammatory diseases

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