Silibinin ameliorates anxiety/depression-like behaviors in amyloid β-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus

Xiaoyu Song; Bo Liu; Lingyu Cui; Biao Zhou; Weiwei Liu; Fanxing Xu; Toshihiko Hayashi; Shunji Hattori; Yuko Ushiki-Kaku; Shin-Ichi Tashiro; Takashi Ikejima

doi:10.1016/j.physbeh.2017.07.023

Silibinin ameliorates anxiety/depression-like behaviors in amyloid β-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus

Physiol Behav. 2017 Oct 1:179:487-493. doi: 10.1016/j.physbeh.2017.07.023. Epub 2017 Jul 19.

Authors

Affiliations

¹ China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China; Medical Research Center, Shenzhen University Health Science Center, Shenzhen 518060, China.
² China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
³ Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017, Japan.
⁴ Department of Medical Education & Primary Care, Kyoto Prefectural University of Medicine, Kajiicho 465, Kamikyo-ku, Kyoto City, Kyoto 602-8566, Japan.
⁵ China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: ikejimat@vip.sina.com.

PMID: 28735062
DOI: 10.1016/j.physbeh.2017.07.023

Abstract

Depression is one of the most frequent psychiatric disorders of Alzheimer's disease (AD). Depression and anxiety are associated with increased risk of developing AD. Silibinin, a flavonoid derived from milk thistle (Silybum marianum), has been used as a hepato-protectant in the clinical treatment of liver diseases. In this study, the effect of silibinin on Aβ-induced anxiety/depression-like behaviors in rats was investigated. Silibinin significantly attenuated anxiety/depression-like behaviors caused by Aβ1-42-treatment as shown in tail suspension test (TST), elevated plus maze (EPM) and forced swimming tests (FST). Moreover, silibinin was able to attenuate the neuronal damage in the hippocampus of Aβ1-42-injected rats. Silibinin-treatment up-regulated the function through BDNF/TrkB pathway and attenuated autophagy in the hippocampus. Our study provides a new insight into the protective effects of silibinin in the treatment of anxiety/depression.

Keywords: Anxiety; Autophagy; BDNF; Depression; Silibinin.

MeSH terms

Alzheimer Disease / drug therapy*
Alzheimer Disease / metabolism
Alzheimer Disease / pathology
Amyloid beta-Peptides
Animals
Anxiety / drug therapy*
Anxiety / metabolism
Anxiety / pathology
Autophagy / drug effects
Brain-Derived Neurotrophic Factor / metabolism
Depression / drug therapy*
Depression / metabolism
Depression / pathology
Disease Models, Animal
Donepezil
Dose-Response Relationship, Drug
Hippocampus / drug effects*
Hippocampus / metabolism
Hippocampus / pathology
Indans / pharmacology
Male
Neurons / drug effects
Neurons / metabolism
Neurons / pathology
Neuroprotective Agents / chemistry
Neuroprotective Agents / pharmacology
Peptide Fragments
Piperidines / pharmacology
Psychotropic Drugs / chemistry
Psychotropic Drugs / pharmacology*
Rats, Sprague-Dawley
Receptor, trkB / metabolism
Signal Transduction / drug effects
Silybin
Silymarin / chemistry
Silymarin / pharmacology*
Up-Regulation / drug effects

Substances

Amyloid beta-Peptides
Brain-Derived Neurotrophic Factor
Indans
Neuroprotective Agents
Peptide Fragments
Piperidines
Psychotropic Drugs
Silymarin
amyloid beta-protein (1-42)
Silybin
Donepezil
Ntrk2 protein, rat
Receptor, trkB