Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway.
Major depression is a common long-lasting or recurrent psychiatric disease with high lifetime prevalence and high incidence of suicide. The main purpose of the current study was to verify whether liquiritigenin conferred an antidepressant-like effect on the depressive mouse model established by unpredictable chronic mild stress (UCMS) and explore its possible mechanism. The results of depression-related behaviors including sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) indicated that both liquiritigenin (7.5mg/kg, 15mg/kg) and fluoxetine (20mg/kg) dramatically improved the depression symptoms. Enzyme-linked immunosorbent assay (ELISA) revealed that treatment with liquiritigenin significantly reduced the concentrations of pro-inflammatory cytokines including interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α in serum and hippocampus. Compared with the UCMS group, the administrations of liquiritigenin, increased levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and decreased Malondialdehyde (MDA) content. Meanwhile, glucocorticoids (GC) content was reduced in the liquiritigenin group, which suggested that liquiritigenin exhibiting the ameliorative effect on activated hypothalamic-pituitary-adrenal (HPA) axis stimulated with UCMS. Mice treated with liquiritigenin showed restored levels of neurotransmitter norepinephrine (NE) and serotonin (5-HT). Western blot analysis displayed up-regulated expressions of p-phosphatidylinositol 3-kinase (PI3K), p-Akt, p- mammalian target of rapamycin (mTOR), p-tropomyosin-related kinase B (TrkB), brain-derived neurotrophic factor (BDNF). Thus, it was supposed that liquiritigenin might be useful for the treatment of chronic depression possibly through PI3K/Akt/mTOR mediated BDNF/TrkB pathway.
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: taoweiweinanjing@126.com.
Weiwei
W
Tao
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Yu
Y
Dong
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Qiang
Q
Su
College of Pharmacy, Ningxia Medical University, Ningxia 750004, China.
Hanqing
H
Wang
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Yanyan
Y
Chen
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Wenda
W
Xue
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Chang
C
Chen
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Baomei
B
Xia
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jinao
J
Duan
Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: chengang@njucm.edu.cn.
Gang
G
Chen
D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D005508:Food Deprivation; D005518:Food Preferences; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009638:Norepinephrine / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013315:Stress, Psychological / Q000150:complications; D014868:Water Deprivation
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D044950:Flavanones; D017382:Reactive Oxygen Species; D012701:Serotonin; D019869:Phosphatidylinositol 3-Kinases; C083152:liquiritigenin; D009638:Norepinephrine
BDNF/TrkB; Depression; Liquiritigenin; PI3K/Akt/mTOR