Protective Effect of Stachydrine Against Cerebral Ischemia-Reperfusion Injury by Reducing Inflammation and Apoptosis Through P65 and JAK2/STAT3 Signaling Pathway.

Li Li,Wenjun Zhu,Kangyuan Hu,Lili Sun,Junqin Mao,Yan Qiu

doi:10.3389/fphar.2020.00064

Abstract

Stachydrine, a constituent of Leonurus japonicus Houtt which also called Japanese motherwort has been shown to improve vascular microcirculation and ameliorate endothelial dysfunction. This study investigated the neuroprotective effect of stachydrine. Male Sprague-Dawley (SD) rats were randomly divided into sham, control, and stachydrine groups. The neurological deficit score was evaluated and the infarct size of the brain was measured using 2,3,5-triphenyltetra-zolium (TTC) chloride staining assay, and the pathological changes in the brain tissues were examined by HE staining. Nissl and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) staining were performed to assess the numbers of Nissl bodies and the levels of apoptosis in the neurons. The activities of superoxide dismutase (SOD) and the levels of malondialdehyde (MDA) were also measured. The release of inflammatory factors IL-1β and TNF-α were detected by Enzyme-linked immunosorbent assay (ELISA). Compared with the control group, the stachydrine group showed a significant prevention of neurological deficit, as indicated by the reduced infarct volume in the brain. Moreover, the stachydrine treatment reduced the activities of SOD, the levels of MDA and decreased the amount of IL-1β, and TNF-α, indicating that it could function to decrease the level of inflammation, thus reducing brain damage. The ischemic stroke model of PC12 cells was prepared via oxygen-glucose deprivation (OGD) protocol for 6 h. The expression of P65 and JAK2/STAT3 signaling pathway related proteins was measured by western blot. The treatment group was found to have the survival rate of PC12 cells improved and the release of inflammatory factors reduced when compared with the OGD group. This study demonstrated that stachydrine could improve nerve function by inhibiting the phosphorylation of P65/JAK2 and STAT3.

Highlights

Stroke is the second leading cause of death in the industrialized countries and the leading cause of acquired adult disability (Go et al, 2013)
In this study we focused on rats and PC12 cells, because stachydrine was reported to produce a protective effect on cerebral ischemic reperfusion damage in rats, enhancing the survival of PC12 cells after oxygen-glucose deprivation (OGD)
Since oxidative stress plays an important role in ischemiareperfusion injury, we investigated the effect of stachydrine on superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in the brain tissue and serum

Summary

Introduction

Stroke is the second leading cause of death in the industrialized countries and the leading cause of acquired adult disability (Go et al, 2013). It was estimated that there would be 1.5 million stroke patients in Europe each year till 2025 Thrombolysis is well recognized to be the only effective therapy for stroke; approximately 5% of the patients treated this way are at a high risk of intracranial hemorrhagic transformation (Campos et al, 2013). Ischemic stroke was reported to show a complex pathophysiological course involving a plethora of distinct molecular and cellular pathways (Wang et al, 2014). It is still imperative that we pursue a consistently effective therapy for stroke

Methods

Results

Conclusion