Proteomics‐based screening of the target proteins associated with antidepressant‐like effect and mechanism of Saikosaponin A

Abstract

Depression is a commonly occurring neuropsychiatric disease with an increasing incidence rate. Saikosaponin A (SA), a major bioactive component extracted from Radix Bupleuri, possesses anti‐malignant cell proliferation, anti‐inflammation, anti‐oxidation and liver protective effects. However, few studies have investigated SA’s antidepressant effects and pharmacological mechanisms of action. Our study aimed to explore the anti‐depression effect of SA and screen the target proteins regulated by SA in a rat model of chronic unpredictable mild stress (CUMS)‐induced depression. Results showed that 8‐week CUMS combined with separation could successfully produce depressive‐like behaviours and cause a decrease of dopamine (DA) in rat hippocampus, and 4‐week administration of SA could relieve CUMS rats’ depressive symptoms and up‐regulated DA content. There were 15 kinds of significant differentially expressed proteins that were detected not only between the control and CUMS groups, but also between the CUMS and SA treatment groups. Proline‐rich transmembrane protein 2 (PRRT2) was down‐regulated by CUMS while up‐regulated by SA. These findings reveal that SA may exert antidepressant effects by up‐regulating the expression level of PRRT2 and increasing DA content in hippocampus. The identification of these 15 differentially expressed proteins, including PRRT2, provides further insight into the treatment mechanism of SA for depression.

Comparative proteomic analysis provides insight into the key proteins as potential targets underlying the effect of malachite green against Ichthyophthirius multifiliis

“…One such approach was that of the isobaric tag for relative and absolute quantification (iTRAQ) quantitative technique. A latest study using an iTRAQ‐based method suggested the proline‐rich transmembrane protein 2 played a crucial role in rat model of chronic unpredictable mild stress (CUMS) with saikosaponin A treatment and provided novel candidate target of the anti‐depression mechanism of saikosaponin A (Guo et al., 2020). In addition, another study also identified rapamycin protein kinase (mTOR) signalling as an important target of panduratin A by iTRAQ proteomic analysis (Lai et al., 2015).…”

An Integrative Pharmacology-Based Strategy to Uncover the Mechanism of Xiong-Pi-Fang in Treating Coronary Heart Disease with Depression

“…Rosmarinic acid can treat neurodegenerative diseases via anti-neuroinflammatory activity ( Wei et al, 2018 ). Furthermore, saponins, such as saikosaponin A, are the major bioactive component extracted from Radix Bupleuri ( Chen et al, 2018 ; Liu R et al, 2018 ) and have anti-inflammatory and antioxidant pharmacological activities, as well as a good therapeutic effect on many diseases of the central nervous system and cardiovascular system ( Guo et al, 2020 ). Flavonoids, such as hesperidin and hesperetin, can inhibit inflammatory reactions and oxidative stress, and protect nerve cells and vascular endothelium ( Hwang et al, 2012 ; Van Rymenant et al, 2017 ).…”

A Study of Icariin Modulating Hippocampal Neurogenesis in Depression Based on Quantitative CSF Proteomics

“…A large number of studies have con rmed that abnormal ribosomal proteins expression or transcription exists in patients with depression and animal models. Most of such studies have observed that the expression of ribosomal proteins is up-regulated or increased transcription in blood, liver, hippocampus and other tissues of depressed individuals [23][24][25]. It has been also observed that the expression of ribosomal proteins in the hippocampus of rats was signi cantly down-regulated under 3-week exposure to CUMS [26].…”