Conclusion
Our study demonstrated that SalB relieved CMS-induced depressive-like state through the mitigation of inflammatory status, oxidative stress, and the activation of AMPK/SIRT1 signaling pathway.
Methods
The rats were randomly divided into three groups: control group with no stressor, CMS group and CMS+SalB (30 mg/kg/d) group. After administration for 28 consecutive days, the behavior tests were performed. The rats were sacrificed after behavior tests, and the brain tissues were collected for biochemical analysis.
Results
It was observed that the administration of SalB for 28 consecutive days successfully corrected the depressive-like behaviors in CMS-treated rats. SalB could effectively reduce the gene expression of pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α), as well as nuclear factor-kappa B (NF-κB) p65 protein. In addition, inhibitor of NF-κB (IκB) protein expression was significantly increased after the administration of SalB. Moreover, SalB could effectively decrease protein expression of oxidative stress markers such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) and increase the activity of catalase (CAT). SalB treatment also reversed CMS-induced inhibition of Nrf2 signaling pathway, along with increasing the mRNA expression of NAD(P)H:quinone oxidoreductase (NQO-1) and heme oxygenase 1 (HO-1). Regarding the endoplasmic reticulum (ER) stress markers, the protein expressions of C/EBP-homologous protein (CHOP) and glucose-regulated protein 78 kD (GRP78) were also significantly reduced after SalB administration. Furthermore, the supplementation of SalB could effectively activate the AMPK/SIRT1 signaling pathway, which indicated significant increase in pAMPK/AMPK ratio and SIRT1 protein expression.