Neuroprotective Effects of Cornus officinalis on Stress-Induced Hippocampal Deficits in Rats and H2O2-Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells.

Weishun Tian,Jeong-Hwi Cho,Byung-Yong Park,Jing Zhao,Sang-Ki Kim,Md Rashedunnabi Akanda,Jeong-Ho Lee,Yu-Jin Choi

doi:10.3390/antiox9010027

Abstract

Oxidative stress plays a vital role in neurodegenerative diseases. Cornus officinalis (CC) has a wide range of pharmacological activities (e.g., antioxidant, neuroprotective, and anti-inflammatory). The present study was undertaken to elucidate the neuroprotective mechanism of CC and fermented CC (FCC) on stress and H2O2-induced oxidative stress damage in rats and SH-SY5Y cells. A dose of 100 mg/kg CC or FCC was orally administered to rats 1 h prior to immobilization 2 h per day for 14 days. CC, especially FCC administration decreased immobility time in forced swim test (FST), effectively alleviated the oxidative stress, and remarkably decreased corticosterone, β-endorphin and increased serotonin levels, respectively. In cells, CC and FCC significantly inhibited reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) release and significantly increased the genes expression of antioxidant and neuronal markers, such as superoxide dismutase (SOD), catalase (CAT), and brain-derived neurotrophic factor (BDNF). Moreover, the pro-apoptotic factor Bax and anti-apoptotic factor Bcl-2 (Bax/Bcl-2) ratio was regulated by CC and FCC pretreatment. Both in rats and cells, CC and FCC downregulated mitogen-activated protein kinase (MAPK) phosphorylation. Taken together, these results demonstrated that CC and particularly FCC ameliorated oxidative stress and may be used on the neuroprotection.

Highlights

Stress is a feeling of emotional or physical tension
Loganin was identified in water extracts of CC or fermented CC (FCC) using HPLC analysis (Figure 1a)
HLPC analysis results, we suspected this compound is morroniside that contented in CC extract and will be investigated in the future

Summary

Introduction

Stress is a feeling of emotional or physical tension. Long-term exposure to stress dampens learning and memory, and causes a number of diseases, including depression, insomnia, anxiety, and post-traumatic stress disorder [1]. Immobilization stress is widely used to induce depressive-like and anxiety-like behaviors, and hippocampal neuronal damage in rodents [2,3]. The hippocampus is one of the most stress-prone targets because it expresses many glucocorticoid and mineralocorticoid receptors [4,5]. Stress alters hippocampal neuronal activity and synaptic plasticity, Antioxidants 2020, 9, 27; doi:10.3390/antiox9010027 www.mdpi.com/journal/antioxidants. Antioxidants 2020, 9, 27 increases hippocampal glucocorticoid receptor activation, and reduces neuronal cell survival and neurogenesis [6,7,8]. The excessive production of free radicals causes oxidative damage to the brain [9,10]. Oxidative stress is induced by an imbalance between the generation of reactive oxygen species (ROS) and the ability of biological systems to detoxify active intermediates.

Methods

Results

Discussion

Conclusion