Curcumin Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors via Restoring Changes in Oxidative Stress and the Activation of Nrf2 Signaling Pathway in Rats.

Dehua Liao,Chuanfeng Lv,Ni Liu,Yi Wu,Minghui Long,Dunwu Yao,Pei Jiang,Lizhi Cao

doi:10.1155/2020/9268083

Abstract

Accumulating evidence has demonstrated that oxidative stress is associated with depression. Our present study aimed at investigating the antidepressant effect and the possible mechanisms of curcumin (CUR) in chronic unpredictable mild stress- (CUMS-) induced depression model in rats. After exposure to CUMS for four weeks, the rats showed depressive-like behavior, and the depressive-like behaviors in CUMS-treated rats were successfully corrected after administration of CUR. In addition, CUR could effectively decrease protein expression of oxidative stress markers (Nox2, 4-HNE, and MDA) and increase the activity of CAT. CUR treatment also reversed CUMS-induced inhibition of Nrf2-ARE signaling pathway, along with increasing the mRNA expression of NQO-1 and HO-1. Furthermore, the supplementation of CUR also increased the ratio of pCREB/CREB and synaptic-related protein (BDNF, PSD-95, and synaptophysin). In addition, CUR could effectively reverse CUMS-induced reduction of spine density and total dendritic length. In conclusion, the study revealed that CUR relieves depressive-like state through the mitigation of oxidative stress and the activation of Nrf2-ARE signaling pathway.

Highlights

As one of the most common neuropsychiatric illness, depression has affected 300 million people of all ages in the modern world [1]
Our study observed that the number of crossing (Figure 2(e), p < 0:05) and rearing (Figure 2(f), p < 0:01) in OPT was all significantly decreased in the CUMS group
The immunohistochemical staining results of 8-OHDG and Nox2 are shown in Figure 4(a); the results showed that the expressions of 8-OHDG and Nox2 were all increased in CUMS-treated rats when compared to control group, and the supplementation of CUR markedly moderated CUMS-induced increasing of 8-OHDG and Nox2

Summary

Introduction

As one of the most common neuropsychiatric illness, depression has affected 300 million people of all ages in the modern world [1]. Many chemical treatments are used for depression, such as tricyclic antidepressants, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors [4, 5]. Increasing evidence suggested that oxidative stress is responsible for the development of depression [9]. Oxidative stress mainly focused on brain which has a limited amount of antioxidant capacity [10]. It was reported that antidepressants could effectively reduced oxidative damage in depressed patients [11, 12]. The antioxidant subjects like polyphenolic compounds exhibit antidepressant activity in experimentally induced depression models by modulating the brain oxidative stress status [13]

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Conclusion