Oleanolic Acid Alleviates Cerebral Ischemia/Reperfusion Injury via Regulation of the GSK-3β/HO-1 Signaling Pathway.

Kaili Lin,Peili Zhu,Ying Wang,Zhang Zhang,Zhu Zhang,Shiqing Zhang,Xiaoli Jiang,Qiudi Deng,Ken Kin Lam Yung

doi:10.3390/ph15010001

Kaili Lin, Peili Zhu + Show 7 more

Open Access

https://doi.org/10.3390/ph15010001

Copy DOI

Abstract

Oleanolic acid (OA), a bioactive ingredient of Panax ginseng, exhibits neuroprotective pharmacological effects. However, the protective role of OA in cerebral ischemia and involved mechanisms remain unclear. This study attempted to explore the therapeutic effects of OA both in vitro and in vivo. OA attenuated cytotoxicity and overproduction of intracellular reactive oxygen species (ROS) by regulation of glycogen synthase kinase-3β (GSK-3β)/heme oxygenase-1 (HO-1) signal in oxygen-glucose deprivation/reoxygenation (OGD/R)-exposed SH-SY5Y cells. Additionally, OA administration significantly reduced the area of cerebral infarction and the neurological scores in the rat models of cerebral ischemia with middle cerebral artery occlusion (MCAO). The OA administration group showed a higher percentage of Nissl+ and NeuN+ cells, along with lower TUNEL+ ratios in the infarct area of MCAO rats. Moreover, OA administration reduced ROS production while it suppressed the GSK-3β activation and upregulated the HO-1 expression in infarcted tissue. Our results illustrated that OA significantly counteracted cerebral ischemia-mediated injury through antioxidant effects induced by the regulation of the GSK-3β/HO-1 signaling pathway, implicating OA as a promising neuroprotective drug for the therapy of ischemic stroke.

Highlights

Introduction published maps and institutional affilIschemic stroke accounts for ~80% of all cases of stroke, which ranks as the second leading cause of death globally [1]
We monitored the neuroprotective effects of oleanolic acid (OA) in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced SH-SY5Y cell model of ischemic injury
Immunofluorescent NeuN staining revealed that the proportion of NeuN+ cells in the infarct areas was dramatically decreased in the middle cerebral artery occlusion (MCAO) group compared to the sham group. This reduction was markedly ameliorated following OA administration in a dose-dependent manner (Figure 3C,D). These findings suggested that OA administration significantly and dose-dependently reduced infarct volumes untreatedin significantly and dose-dependently ameliorated neuronal damage in compared infarctedtoregions

Summary

Introduction

Ischemic stroke accounts for ~80% of all cases of stroke, which ranks as the second leading cause of death globally [1]. Despite the significant pharmaceutical advances that have been made in recent years, clinically effective drugs for the treatment of ischemic strokes are still lacking [2]. Traditional Chinese medicine (TCM) is considered a huge source of novel drugs and compounds for therapy in neurological diseases [3]. Ginseng (Panax ginseng), a popular herb used in TCM, has been confirmed to play a protective role in cerebral ischemia in vivo [4]. The accumulation of reactive oxygen species (ROS) after an ischemic stroke leads to oxidative stress in the brain, which is one of the fundamental mechanisms underlying iations Among the bioactive ingredients of ginseng, the triterpenoid oleanolic acid (OA) has exhibited favorable pharmacological properties—including neuroprotective, anticancer, and anti-inflammatory activities [5].

Methods

Results

Discussion

Conclusion