Matrine Exerts Antidepressant-Like Effects on Mice: Role of the Hippocampal PI3K/Akt/mTOR Signaling

Abstract

BackgroundCurrent antidepressants in clinical use always take weeks or even months to exert full therapeutic effects, and sometimes have serious side effects. Thus, it is very necessary to develop novel antidepressants with better efficacy and fewer adverse effects. The present study focused on investigating the antidepressant potential of matrine and its possible mechanisms of action.MethodsThe forced swim test, tail suspension test, and chronic unpredictable mild stress model of depression were used to reveal the antidepressant-like effects of matrine on mice. Western blotting, immunohistochemistry, and lentivirus were further used together to explore the antidepressant mechanism of matrine.ResultsIt was found that matrine exhibited significant antidepressant actions in the forced swim test and tail suspension test without affecting the locomotor activity of mice. Chronic matrine administration fully reversed the chronic unpredictable mild stress-induced depressive-like symptoms in forced swim test, tail suspension test, and sucrose preference test. After that, western blotting analysis revealed that chronic matrine treatment restored the decreasing effects of chronic unpredictable mild stress on the PI3K/Akt/mammalian target of rapamycin signaling in hippocampus, but not prefrontal cortex. Furthermore, pharmacological and genetic blockade of the PI3K/Akt/mammalian target of rapamycin signaling in hippocampus abolished the antidepressant actions of matrine on mice.ConclusionsTaken together, matrine produces antidepressant-like effects on mice via promoting the hippocampal PI3K/Akt/ mammalian target of rapamycin signaling.

Antidepressant‐like effects of 20(S)‐protopanaxadiol in a mouse model of chronic social defeat stress and the related mechanisms

“…TrkB‐induced PI3K activity leads to AKT activation, which, once activated, leads to the phosphorylation of mTOR at serine 2448, thereby promoting downstream molecules (Y. Lu et al, ). It has been reported that the upregulation of PI3K/AKT/mTOR signalling in the prefrontal cortex and hippocampus leads to rapid and consistent antidepressant‐like effects (Z. Wu et al, ). In agreement with previous studies, we observed CSDS‐induced depressive symptoms and consequent PI3K/AKT/mTOR signalling downregulation.…”

A Systematic Review of the Pharmacology, Toxicology and Pharmacokinetics of Matrine

“…It was demonstrated that MT alleviated anxiety and depression symptoms in a mouse model of burn injury by inhibiting JNK-mediated apoptosis/inflammatory signaling, oxidative stress, and reversing the burn-induced down-regulation of BDNF/VEGF in the hippocampus (Khan et al, 2020). Furthermore, Wu et al (2018) demonstrated that MT possessed antidepressant-like effect on mice by activating the PI3K/Akt/mTOR signaling pathway in the hippocampus.…”

Effects of different drying methods on the chemical constituents of Lilium lancifolium Thunb. based on UHPLC‐MS analysis and antidepressant activity of the main chemical component regaloside A

“…Its hyperactivity can lead to the accumulation of corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone (CORT), which can lead to neuroinflammation and damage the functional morphology of the brain [20], which is an important risk factor for depression. The phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway is an important signaling pathway involved in neuronal survival, synaptic morphology, structure formation, and synaptic information transmission [21]. Activation of this pathway protects the nerve from multiple stress injuries and is involved in the process underlying the antidepressant effects [22,23].…”