Neuroprotective Effects of Ginsenosides against Cerebral Ischemia.

Zhekang Cheng,Ying Zhu,Meng Zhang,Hongwei Ren,Chengli Ling,Chao Hong,Jianxin Wang,Jing Qin,Tongxiang Liu

doi:10.3390/molecules24061102

Abstract

Ginseng has been used worldwide as traditional medicine for thousands of years, and ginsenosides have been proved to be the main active components for their various pharmacological activities. Based on their structures, ginsenosides can be divided into ginseng diol-type A and ginseng triol-type B with different pharmacological effects. In this study, six ginsenosides, namely ginsenoside Rb1, Rh2, Rg3, Rg5 as diol-type ginseng saponins, and Rg1 and Re as triol-type ginseng saponins, which were reported to be effective for ischemia-reperfusion (I/R) treatment, were chosen to compare their protective effects on cerebral I/R injury, and their mechanisms were studied by in vitro and in vivo experiments. It was found that all ginsenosides could reduce reactive oxygen species (ROS), inhibit apoptosis and increase mitochondrial membrane potential in cobalt chloride-induced (CoCl2-induced) PC12 cells injury model, and they could reduce cerebral infarction volume, brain neurological dysfunction of I/R rats in vivo. The results of immunohistochemistry and western blot showed that the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), silencing information regulator (SIRT1) and nuclear transcription factor P65 (NF-κB) in hippocampal CA1 region of some ginsenoside groups were also reduced. In general, the effect on cerebral ischemia of Rb1 and Rg3 was significantly improved compared with the control group, and was the strongest among all the ginsenosides. The effect on SIRT1 activation of ginsenoside Rb1 and the inhibition effect of TLR4/MyD88 protein expression of ginsenoside Rb1 and Rg3 were significantly stronger than that of other groups. The results indicated that ginsenoside Rg1, Rb1, Rh2, Rg3, Rg5 and Re were effective in protecting the brain against ischemic injury, and ginsenoside Rb1 and Rg3 have the strongest therapeutic activities in all the tested ginsenosides. Their neuroprotective mechanism is associated with TLR4/MyD88 and SIRT1 activation signaling pathways, and they can reduce cerebral ischemic injury by inhibiting NF-κB transcriptional activity and the expression of proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).

Highlights

Cerebral ischemia is a common refractory brain disease that seriously endangers human health.There are 15 million new stroke patients worldwide each year, and six million people die from the disease, among which ischemic stroke accounts for 80% [1,2]
2A), 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide assaycorrelated (MTT assay, 2A),2 and we found that the survival rates of PC12 cells were inversely withFigure the CoCl and we foundWhen that the theconcentration survival rates of PC12 cells were inversely correlated with the CoCl2 concentration
The results showed that ginsenoside Rb1 and Rg3 could significantly improve the neurological score and reduce the area of middle cerebral artery occlusion (MCAO) cerebral infarction

Summary

Introduction

Cerebral ischemia is a common refractory brain disease that seriously endangers human health. There are 15 million new stroke patients worldwide each year, and six million people die from the disease, among which ischemic stroke accounts for 80% [1,2]. Cerebral ischemia-reperfusion (I/R) injury is the damage caused by the recovery of blood supply after a certain period of brain tissue ischemia. The dysfunction and structural damage of the brain tissue will be aggravated. Inflammation plays an important role in the process of ischemic stroke. In the initial stage of inflammation, microglia and astrocytes are activated in the cerebral ischemia, and cytokines and chemokines cross the activated vascular wall to reach the penumbra [6,7]

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