Cissus verticillata Extract Decreases Neuronal Damage Induced by Oxidative Stress in HT22 Cells and Ischemia in Gerbils by Reducing the Inflammation and Phosphorylation of MAPKs.

Woosuk Kim,Hyo Young Jung,Soo Young Choi,Dong-Sool Yu,Yong-Bok Jo,Beom-Goo Kang,Soon-Sung Lim,Hyun Jung Kwon,Dae Won Kim,In Koo Hwang

doi:10.3390/plants10061217

Abstract

In the present study, we examined the effects of Cissus verticillata leaf extracts (CVE) against hydrogen peroxide (H2O2)- and ischemia-induced neuronal damage in HT22 cells and gerbil hippocampus. Incubation with CVE produced concentration-dependent toxicity in HT22 cells. Significant cellular toxicity was observed with >75 μg/mL CVE. CVE treatment at 50 μg/mL ameliorated H2O2-induced reactive oxygen species formation, DNA fragmentation, and cell death in HT22 cells. In addition, incubation with CVE significantly mitigated the increase in Bax and decrease in Bcl-2 induced by H2O2 treatment in HT22 cells. In an in vivo study, the administration of CVE to gerbils significantly decreased ischemia-induced motor activity 1 d after ischemia, as well as neuronal death and microglial activation 4 d after ischemia, respectively. CVE treatment reduced the release of interleukin-1β, interleukin-6, and tumor necrosis factor-α 6 h after ischemia. Furthermore, CVE treatment significantly ameliorated ischemia-induced phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase 1/2, and p38. These results suggest that CVE has the potential to reduce the neuronal damage induced by oxidative and ischemic stress by reducing the inflammatory responses and phosphorylation of MAPKs, suggesting that CVE could be a functional food to prevent neuronal damage induced by ischemia.

Highlights

Hydrogen peroxide (H2O2) is a well-known reactive oxygen species (ROS) and causes oxidative stress in various cell lines, including HT22 hippocampal cells [1,2,3]
We validated the cellular toxicity of Cissus verticillata leaf extracts (CVE) in HT22 hippocampal cells based on the cell viability, ROS formation, and DNA fragmentation
We selected the optimal concentration of 50 μg/mL, which did not show significant changes in cell viability, ROS formation, and DNA fragmentation in HT22 cells

Summary

Introduction

Hydrogen peroxide (H2O2) is a well-known reactive oxygen species (ROS) and causes oxidative stress in various cell lines, including HT22 hippocampal cells [1,2,3]. The hippocampus, thalamus, and neocortex are highly susceptible to transient forebrain ischemia in gerbils [5,6]. Damage to the hippocampus causes hyperactivity and memory impairment due to hippocampal neuronal damage [7,8]. Ischemia is caused by an insufficient blood supply which does not meet the metabolic requirements in the brain, leading to brain tissue damage [9]. Interruption of blood vessels and reperfusion enormously increases the formation of ROS because of the high content of unsaturated fatty acids in neurons [10]. Increased ROS react with unsaturated fatty acids in membranes and DNA in the nucleus and causes the neuronal damage. Cell death mechanisms have been widely elucidated [16,17], but few therapeutics have been approved for the treatment of ischemia

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Results

Conclusion