The RIG-I Signal Pathway Mediated Panax notoginseng Saponin Anti-Inflammatory Effect in Ischemia Stroke.

Chujun Zhang,Qinghong Du,Yanhong Hu,Sai Zhang,Jiabao Ma,Tianshi Sun,Yixin Dong,Soyeon Kang,Weihong Li,Shihao Liu,Lanxiang Wang,Tenghui Li,Fan Zhang,Muhammad Ali Hashmi

doi:10.1155/2021/8878428

Abstract

Panax notoginseng saponins (PNS), the main bioactive constituents of a traditional Chinese herb Panax notoginseng, were commonly used for ischemic stroke in China. However, the associated cellular and molecular mechanisms of PNS have not been well examined. This study aimed to decipher the underlying molecular target of PNS in the treatment of cerebral ischemia. The oxygen-glucose-deprived (OGD) model of rat brain microvascular endothelial cells (BMECs) was used in this study. The alteration of gene expression in rat BMECs after PNS treatment was measured by microarray and indicated that there were 38 signaling pathways regulated by PNS. Among them, RIG-I receptor and related signaling molecules TNF receptor-associated factor 2 (Traf2) and nuclear factor-kappa B (NF-κB) were significantly suppressed by PNS, which was verified again in OGD-induced BMECs measured by FQ-PCR and western blotting and in middle cerebral artery occlusion (MCAO) rats measured by immunohistochemistry. The levels of TNF-α, IL-8, and the downstream cytokines regulated by RIG-I receptor pathway were also decreased by PNS. Meanwhile, the neurological evaluation, hematoxylin and eosin (HE) staining, and Evans blue staining were conducted to evaluate the effect of PNS in MCAO rats. Results showed PNS significantly improved functional outcome and cerebral vascular leakage. Flow cytometry showed the number of the inflammatory cells infiltrated in brain tissue was decreased in PNS treatment. Our results identified that RIG-I signaling pathway mediated anti-inflammatory properties of PNS in cerebral ischemia, which provided the novel insights of PNS application in clinics.

Highlights

Ischemic cerebral apoplexy, which is more commonly known as stroke, is an acute condition compromise of the cerebral perfusion or vasculature or cerebrovascular accident and one of the leading causes of death worldwide. e initial ischemic injury can trigger a cascade of detrimental events including glutamate-associated excitotoxicity, inflammation, oxidant stress, and apoptosis [1, 2]
The microarray was used to screen the genes regulated by Panax notoginseng saponins (PNS) in the oxygenglucose deprivation- (OGD-) induced brain microvascular endothelial cells (BMECs). rough the pathway analysis, we found that retinoic acid-inducible gene-I (RIG-I) reception signaling pathway was downregulated by PNS. en, the change of RIG-I signaling pathway and the downstream effect was further verified in in vitro and vivo ischemic model
38 Signaling Pathways Regulated by PNS Were Screened Out by Genomic Analysis. e differentially expressed genes in OGD-induced BMECs treated with or without PNS were screened by Affymetrix GeneChip Array. e microarray results showed there were 1195 differentially expressed genes in the PNS group compared to BMECs of the OGD group, including 552 upregulated genes and 643 downregulated genes. e most significantly affected genes included those coding for proteins involved in oxidation-reduction process, transmembrane transport, ion transport, and immune response

Summary

Introduction

Ischemic cerebral apoplexy, which is more commonly known as stroke, is an acute condition compromise of the cerebral perfusion or vasculature or cerebrovascular accident and one of the leading causes of death worldwide. e initial ischemic injury can trigger a cascade of detrimental events including glutamate-associated excitotoxicity, inflammation, oxidant stress, and apoptosis [1, 2]. Ischemic cerebral apoplexy, which is more commonly known as stroke, is an acute condition compromise of the cerebral perfusion or vasculature or cerebrovascular accident and one of the leading causes of death worldwide. E initial ischemic injury can trigger a cascade of detrimental events including glutamate-associated excitotoxicity, inflammation, oxidant stress, and apoptosis [1, 2]. It has been known that ischemic stroke can induce acute inflammation in ischemic core and penumbra, which aggravates primary brain damage [3]. Pharmacochemical studies showed that Panax notoginseng contains various chemical components such as saponins, amino acids, polysaccharides, and flavonoids [8] with Panax notoginseng saponin (PNS) being the most important one. Recent studies suggested that PNS can increase blood flow and inhibit inflammation and platelet aggregation as well as attenuate oxidative stress [9, 10]

Results

Discussion

Conclusion