Tanshinone IIA Protects Against Cerebral Ischemia Reperfusion Injury by Regulating Microglial Activation and Polarization via NF-κB Pathway.

Zhibing Song,Dahai Yu,Yuefan Zhang,Shanshan Deng,Tiejun Li,Jingjing Feng,Qian Zhang

doi:10.3389/fphar.2021.641848

Abstract

Tanshinone IIA, a fat-soluble diterpenoid isolated from Salvia miltiorrhiza Bunge, has been shown to attenuate the cerebral ischemic injury. The aim of this study was to examine the effects on neuroprotection and microglia activation of Tanshinone IIA. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO). We found that Tanshinone IIA significantly reduced infarction volume, alleviated neuronal injuries, reduced the release of TNF-α, IL-1β, and IL-6, increased SOD activity, and decrease the content of MDA in MCAO rats. Hematoxylin and eosin staining, Nissl staining, TUNEL staining and immunofluorescence staining showed that Tanshinone IIA improved the distribution and morphology of neurons in brain tissues and reduced apoptosis. In addition, Co-immunofluorescence staining of rat brain tissues and the mRNA expression levels of CD11b, CD32, iNOS, and Arg-1, CD206, IL-10 in BV2 cells indicated that Tanshinone IIA can downregulate M1 microglia and upregulate M2 microglia in MCAO rats. Further, BV2 microglial cells were subjected to oxygen-glucose deprivation, the protein expression levels were detected by western blot. Tanshinone IIA inhibited the expression levels of NF-κB signaling pathway related proteins. Taken together, this study suggested that Tanshinone IIA modulated microglial M1/M2 polarization via the NF-κB signaling pathway to confer anti-neuroinflammatory effects.

Highlights

Senile neurological diseases stroke has become the third leading cause of death in developed countries and the main cause of global disability (Collaborators, 2018)
Tanshinone IIA (T4952) and 2,3,5-triphenyltetrazolium chloride (TTC) were purchased from Sigma-Aldrich (United States).; BPL (3-n-Butylphthalide, a marketed drug for acute ischemic stroke) (H20100041) was purchased from CSPC (China); BAY-11-7082 (S2913) was purchased from Selleck (United States); Enzyme-linked Immunosorbent Assay (ELISA) Kit was purchased from R&D Systems (United States); superoxide dismutase (SOD) and malondialdehyde (MDA) assay kit were purchased from Nanjing Jiancheng Bioengineering Institute (China); total RNA Kit was purchased from Takara (Japan)
A recent study showed that Tanshinone IIA (20 and 40 mg/kg) reduced brain water content and normalized neurological deficit score after cerebral ischemiareperfusion injury in rats (Wang et al, 2020)

Summary

Introduction

Senile neurological diseases stroke has become the third leading cause of death in developed countries and the main cause of global disability (Collaborators, 2018). The main pathophysiological mechanism of ischemic stroke neurological injury is inflammatory response. Microglia are one of the resident immune cells in the central nervous system. In the case of ischemic stroke, microglia rapidly transform from a resting state to an active “amebic-like” state, releasing a variety of inflammatory and cytotoxic mediators, causing cell damage and death, aggravating brain damage (Zhao et al, 2017; Lamkanfi and Dixit, 2014). M2 type can promote nerve repair during central nervous system injury (Chen et al, 2015; Kalkman and Feuerbach, 2016; Liu et al, 2019) and has a vital role in resolving inflammatory responses and debris removal, tissue remodeling, and angiogenesis (Mantovani et al, 2013)

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