Salvianolic Acid B Ameliorates Cerebral Ischemia/Reperfusion Injury Through Inhibiting TLR4/MyD88 Signaling Pathway

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ORIGINAL ARTICLE

Salvianolic Acid B Ameliorates Cerebral Ischemia/Reperfusion Injury Through Inhibiting TLR4/MyD88 Signaling Pathway Yujue Wang,1 Guang Chen,1 Xiangdong Yu,1 Yunchao Li,1 Li Zhang,2 Zongze He,3 Nannan Zhang,4 Xiuping Yang,4 Yansheng Zhao,5 Na Li,6 and Hong Qiu1,7

ABSTRACT—Ischemic stroke can activate multiple transcription factors and cause inflammatory reactions, which involve pattern recognition receptors with immunostimulatory effects. Toll-like receptor 4 (TLR4) is one of the receptors related to innate immunity and several inflammatory reactions. The promising antiinflammatory activity of salvianolic acid B (SAB) had been previously reported, but its effect on ischemic stroke remains unknown. An oxygen-glucose deprivation and reoxygenation (OGD/R) model in vitro and a middle cerebral artery occlusion (MCAO) model in vivo were used in this paper, and the results showned that SAB remarkably increased the viabilities of PC12 cells and primary cortical neurons after OGD/R injury and notably prevented cerebral ischemia/reperfusion (I/R) injury. SAB also significantly ameliorated NeuN release from primary cortical neurons. Further research indicated that the neuroprotection of SAB was completed through inhibiting the TLR4/MyD88/TRAF6 signaling pathway. The blocking of TLR4 by SAB also restrained NF-kB transcriptional activity and pro-inflammatory cytokine responses (IL-1β, IL-6, and TNF-α). These findings supply a new insight that will aid in clarifying the effect of SAB against cerebral I/R injury and provide the development of SAB as a potential candidate for treating ischemic stroke. KEY WORDS: cerebral I/R injury; inflammation; ischemic stroke; SAB; TLR4.

INTRODUCTION

Yujue Wang and Guang Chen contributed equally to this work. 1

Department of Neurosurgery, KaiLuan General Hospital, Tangshan, 063000, China 2 Department of Neurosurgery, Tangshan People’s Hospital, Tangshan, 063000, China 3 Department of Neurosurgery, The Affiliated Hospital of University of Electronic Science and Technology of China & Sichuan Provincial People’s Hospital, Chengdu, 610072, China 4 Department of Neurology, KaiLuan General Hospital, Tangshan, 063000, China 5 Department of Nuclear Magnetic, KaiLuan General Hospital, Tangshan, 063000, China 6 Department of Emergency, Chinese People’s Liberation Army 255 Hospital, Tangshan063000, China 7 To whom correspondence should be addressed at Department of Neurosurgery, KaiLuan General Hospital, Tangshan, 063000, China. E-mail: [email protected]

Ischemic stroke is associated with various risk factors, such as hypertension, atherosclerosis, thrombosis, and diabetes [1]. Approximately 15 million people are subjected to ischemic strokes in the world each year, which mainly result in acquired disability and even death in adults [2]. In spite of this, fibrinolysis is the only therapy for treating stroke [3]. However, the subsequent restoration of blood flow and reoxygenation lead to hemorrhagic transformation, blood–brain barrier disruption, and brain injury [4]. According