Total Saikosaponins Attenuates Depression-Like Behaviors Induced by Chronic Unpredictable Mild Stress in Rats by Regulating the PI3K/AKT/NF-κB Signaling Axis

Abstract

Background. Depression is a major cause of disability and most antidepressant medicines are ineffective owing to their high toxicity and numerous adverse effects. As a result, there is an urgent need to find new effective treatment methods. This paper aims to investigate the effect and mechanism of total saikosaponins (TSS) on depression-like behaviors induced by chronic unpredictable mild stress (CUMS) in rats. Methods. Twenty-four male SD rats were randomly divided into 4 groups: control group, CUMS group, TSS group, and fluoxetine (Flu) group. Then, the following tests were conducted: sucrose preference test, open field test, and elevated plus maze test. Additionally, ELISA was used to detect the levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH) in the serum of the rats as well as the levels of inflammatory cytokines IL-1β, IL-6, and TNF-α in the hippocampus, and Western blot was used for measuring the expression of brain-derived neurotrophic factor (BDNF) protein and related proteins of the PI3K/AKT/NF-κB signaling pathway in the hippocampus. Results. TSS could significantly improve rat behaviors, specifically indicated by increases in sucrose preference, total movement distance, stay time in the central area, number of entries into open arms, time spent in open arms, and a decrease in stay time in the peripheral area. TSS acted to significantly reduce BDNF protein expression and increase the contents of ACTH and CORT in serum as well as the levels of IL-1β, IL-6, and TNF-α in the hippocampal tissue in rats. In addition, it was able to raise the ratios of p-PI3K/PI3K and p-AKT/AKT and decrease the ratio of p-p65/p65 in tissues, which in turn regulated the PI3K/AKT/NF-κB signaling pathway. Conclusions. TSS, through regulating PI3K/AKT/NF-κB signaling axis, can alleviate depression-like behaviors and elevate neuroendocrine hormone levels and inflammatory factor levels.

Polygonum sibiricum polysaccharides exert the antidepressant‐like effects in chronic unpredictable mild stress‐induced depressive mice by modulating microbiota‐gut‐brain axis

“…Furthermore, promoting the neurotrophic factor release, regulating the glutamatergic system function, inhibiting the hippocampal neuronal apoptosis and improving the mitochondrial dysfunction are also related to PI3K/AKT signaling pathway (Jiang et al, 2021). In agreement with previous studies, our results demonstrated that the CUMS procedure induced the activation of TLR4/NF‐κB and the inhibition of the PI3K/AKT signaling pathway in the hippocampus of mice, and both PSP administration and transplantation of PSP‐associated fecal microbiota remarkably reversed these changes (Zhou et al, 2022). These results demonstrated that the inhibition of neuroinflammation by PSP via the MGB axis was related to the PI3K/AKT/TLR4/NF‐κB signaling pathway.…”

“…It has been confirmed that the PI3K/AKT pathway is inhibited in depression animal model induced by chronic stress (Nazeem et al, 2021). The downregulation of the PI3K/AKT signaling pathway can lead to increased phosphorylation of NF‐κB, providing negative feedback regulation to the TLR4/NF‐κB signaling pathway (Zhou et al, 2022). Furthermore, promoting the neurotrophic factor release, regulating the glutamatergic system function, inhibiting the hippocampal neuronal apoptosis and improving the mitochondrial dysfunction are also related to PI3K/AKT signaling pathway (Jiang et al, 2021).…”

An Investigation of the Anti-Depressive Properties of Phenylpropanoids and Flavonoids in Hemerocallis citrina Baroni

“…[63]. Pro-inflammatory cytokines-including IL-6, IL-1β, and TNF-α-were increased in depressed patients' bodies [64]. In this study, CUMS significantly improved the hippocampal levels of IL-6, IL-1β, and TNF-α in rats, while HFPE and HFFE significantly reversed the increase in these pro-inflammatory cytokines.…”

“…According to the inflammatory theory for depression, stress triggers inflammatory processes, which impair the body's ability to produce serotonin and regulate the HPA axis, resulting in depression [63]. Pro-inflammatory cytokines-including IL-6, IL-1β, and TNF-α-were increased in depressed patients' bodies [64]. In this study, CUMS significantly improved the hippocampal levels of IL-6, IL-1β, and TNF-α in rats, while HFPE and HFFE significantly reversed the increase in these pro-inflammatory cytokines.…”

Saikosaponin A and Its Epimers Alleviate LPS-Induced Acute Lung Injury in Mice

“…The total SSs alleviated depression-like behaviors and decreased neuroendocrine hormone and inflammatory factor levels by regulating the PI3K/AKT/NF-κB signaling pathway [ 33 ]. SSD protected mice from APAP-induced hepatotoxicity, mainly by restraining NF-κB- and STAT3-mediated inflammatory signaling [ 34 ].…”