Paeoniflorin ameliorates chronic stress-induced depression-like behavior in mice model by affecting ERK1/2 pathway

Abstract

Depression is a mental and emotional disorder that has made an opening great burden to the society. Paeoniflorin showed remarkable antidepressant-like effects in multiple animal models with depressive disorders. However, the molecule of paeoniflorin on depression is less studied. This study aims to explore the effect and the molecular mechanism of paeoniflorin on depression in a chronic restraint stress (CRS) mice model. CRS model of C57BL/6 J mice was set up. Sucrose preference test (SPT), tail suspension test (TST), open field test (OFT) and forced swimming test (FST) were used to assess depression symptoms. Immunofluorescence staining, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were implemented to detect the expression changes of the proteins involved in extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Results showed that paeoniflorin treatment decreased the degree of depression in the CRS mice. Further analysis showed that the expression of ERK1/2 proteins was significantly downregulated, while paeoniflorin could elevate the expression of ERK1/2 proteins in CRS mice. Finally, it showed that inhibiting signaling ERK1/2 pathway could aggravate the depressive behavior when treatment with ERK-specific inhibitor U0126, while the condition could be partially relieved when treated with paeoniflorin. In conclusion, the present study demonstrated that paeoniflorin attenuated chronic stress-induced depression-like behavior in mice by affecting the ERK1/2 pathway. These findings provided the basis for the molecular mechanism of paeoniflorin on the effect of depression, which support paeoniflorin might act as an important drug in the treatment of depression.

Role of BDNF–TrkB signaling in the antidepressant‐like actions of loganin, the main active compound of Corni Fructus

“…A series of studies indicated that the target of antidepressant drugs was determined by using inhibitors 40,41 . For example, previous studies showed that the antidepressant‐like actions of paeoniflorin, geniposide, and curcumin were blocked by using U0126, LY94002, and SR18292, which identified ERK, PI3K, and PGC‐1α as the targets of the above drugs, respectively 42–44 . This study also used a similar method to diagnose whether TrkB could be used as the antidepressant target of loganin by using the recognized TrkB inhibitor K252a in CUMS‐induced depression–like mice.…”

“…40,41 For example, previous studies showed that the antidepressant-like actions of paeoniflorin, geniposide, and curcumin were blocked by using U0126, LY94002, and SR18292, which identified ERK, PI3K, and PGC-1α as the targets of the above drugs, respectively. [42][43][44] This study also used a similar method to diagnose whether TrkB could be used as the antidepressant target of loganin by using the recognized TrkB inhibitor K252a in CUMS-induced depression-like mice. In this study, behavioral results displayed that 10 and 20 mg/kg loganin significantly reversed the decrease of sucrose intake in SPT induced by CUMS, while K252a blocked the antidepressant-like actions of loganin, suggesting that TrkB might be a target for the antidepressant-like actions of loganin.…”

Quantitative proteomics reveals the therapeutic effects of RFAP against depression via pathway regulation of long-term depression and potentiation

“…All of them presented potential pharmacological mechanisms. Of these, Paeoniflorin possibly plays a neuroprotective effect in improving chronic stress-induced depression and neuronal damage in rats through activation of the ERK-CREB pathway [ 26 , 27 ]. Studies have shown that albiflorin directs antidepressant role by the cytoplasmic phospholipase A2 (cPLA2) -protein kinase B (Akt1)-indoleamine 2,3-dioxidase 1(IDO1) regulatory loop [ 28 ].…”

Icariin prevents depression-like behaviors in chronic unpredictable mild stress-induced rats through Bax/cytoplasm C/caspase-3 axis to alleviate neuronal apoptosis

“…Icariin (ICA) is a flavonoid glucoside isolated from Epimedium brevicornu Maxim , which is frequently used in traditional Chinese medicine (TCM) to treat asthma [19], kidney disease [20], testicular dysfunction [21] and cartilage damage [22]. TCM is often used to treat depression, for example, paeoniflorin improves chronic stress-induced depression behavior in mice model by influencing the ERK1/2 pathway [23]. Zhang et al revealed that Xiaoyao powder can reduce the damage of hippocampal neurons in CUMS-induced hippocampal depression model rats through connexin 43Cx43/GR/brain-derived neurotrophic factor signaling pathway [24].…”