The effect of Piper laetispicum extract (EAE-P) during chronic unpredictable mild stress based on interrelationship of inflammatory cytokines, apoptosis cytokines and neurotrophin in the hippocampus.

Hui Xie,Juan Liu,Jian Chen,Xueru Shi,Yun Kang,Macheng Yan,Hongrui Liu,Shengli Pan,Haixing Shen,Di Jin

doi:10.1186/s12906-015-0747-8

Abstract

BackgroudThe Piper laetispicum C.DC. (Piperaceae) is a traditionally used herb in China for invigorating circulation and reducing stasis, detumescence and analgesia, which is distributed in the southern part of China and the southeastern part of Asia. Previous studies demonstrated that the ethyl acetate extract (EAE-P) of P. laetispicum possesses a significant antidepressant-like effect at doses higher than 60 mg/kg in Kunming (KM) mice, and this effect was not due to an increase in locomotive activity.MethodsTo research this mechanism, in the present study, the chronic unpredictable mild stress (CUMS) model in Sprague–Dawley rats was used to further elucidate behavioral changes and corresponding changes in inflammatory cytokines (TNF-α, IL-6, IL-10), apoptosis cytokines (P53, Bax, Bcl2, caspase-3) and neurotrophin (BDNF) in the hippocampus of EAE-P treatment animals.Results and conclusionsThe results suggest that EAE-P is beneficial to the behavioral outcome of the CUMS model animals, and decreased amounts of inflammatory cytokine IL-6 contributed to the antidepressant-like activation of EAE-P in every dosage group (15, 30, 60 mg/kg). In the low dosage group, down-regulated apoptosis cytokine p53 is associated with EAE-P effect, but it is inflammatory cytokine TNF-α that is related to the effect of EAE-P in the high dosage group. Meanwhile, the P53-dependent antiapoptotic effect of EAE-P may not be through Bcl-2 and Bax modulation. Furthermore, EAE-P showed up-regulated expression of brain-derived neurotrophic factor (BDNF) mRNA and down-regulated apoptosis cytokine caspase-3 mRNA, which was the same change tendency as with Fluoxetine.

Highlights

Depression is one of the most burdensome diseases, usually associated with acute and persistent symptoms leading to life quality impairment [1]
We further demonstrated that the ethyl acetate extract of P. laetispicum (EAE-P) possesses a significantly antidepressantlike effect at doses higher than 60 mg/kg in KM mice and proved that this was not due to an increase in locomotive activity [9]
At the end of the third week, significant differences were observed between the control and model groups, which are the key indicator of successful implementation of the chronic unpredictable mild stress (CUMS) model

Summary

Introduction

Depression is one of the most burdensome diseases, usually associated with acute and persistent symptoms leading to life quality impairment [1]. Extensive studies of herbal medicines potentially useful in the treatment of depression have been conducted. (Piperaceae) is an endemic, climbing, glabrous plant distributed in the southern part of China and the southeastern part of Asia where it is popularly known as Xiao Chang-feng, Shan Hu-jiao, and Ye Hu-jiao. It is traditionally used for invigorating circulation and reducing stasis, detumescence and analgesia in China [7]. We further demonstrated that the ethyl acetate extract of P. laetispicum (EAE-P) possesses a significantly antidepressantlike effect at doses higher than 60 mg/kg in KM mice and proved that this was not due to an increase in locomotive activity [9]

Methods

Results

Conclusion