Antidepressant-like effects of Xiaochaihutang in a rat model of chronic unpredictable mild stress.
BACKGROUND
Xiaochaihutang (XCHT) has been used in China for thousands of years to treat "Shaoyang syndrome", which involves depressive-like symptoms. However, few studies have investigated its antidepressant effects and pharmacological mechanism of action. The present study was designed to confirm the antidepressant effect of XCHT using a chronic unpredictable mild stress (CUMS) model and explore its potential mechanism of action by investigating the monoamine neurotransmitters (dopamine and 5-hydroxytryptamine) and neurotrophins (BDNF and NGF).


METHODS
The CUMS model was established in rats, and the antidepressant effect of XCHT (0.6, 1.7 and 5mg/kg/day, given by gastric gavage for 4 weeks) was investigated using the open field test (OFT), food consumption test and sucrose preference test. The concentrations of 5-HT and DA in the hippocampus were measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD). The expressions of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and their receptors tyrosine receptor kinase B (TrkB) and tyrosine receptor kinase A (TrkA) in the hippocampus were measured by immunohistochemical staining analysis.


RESULTS
CUMS caused a significant decrease in OFT, food consumption and sucrose preference in rats, and these depression-like behaviors were significantly improved by XCHT (1.7 and 5 g/kg/day). Moreover, XCHT significantly increased the concentrations of 5-HT (0.6 and 5 g/kg/day) and DA (5 g/kg/day), and improved the BDNF, NGF, TrkB and TrkA expressions in the hippocampus (1.7 and 5 g/kg/day), which was reduced in CUMS rats.


CONCLUSIONS
The results obtained suggested that XCHT may have therapeutic actions on depression-like behavior induced by CUMS in rats possibly mediated by increasing the monoamine neurotransmitter concentration and neurotrophin expression in the hippocampus.
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China.
Guang Yue
GY
Su
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China.
Jing Yu
JY
Yang
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China.
Fang
F
Wang
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China.
Jie
J
Ma
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China.
Kuo
K
Zhang
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China.
Ying Xu
YX
Dong
Department of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
Shao Jiang
SJ
Song
Department of pharmaceutical analysis, Shenyang Pharmaceutical University, 110016 Shenyang, China.
Xiu Mei
XM
Lu
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: wucf@syphu.edu.cn.
Chun Fu
CF
Wu
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy*; D013395:Sucrose / Q000008:administration & dosage
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D004365:Drugs, Chinese Herbal; C461320:shosaiko-to; D012701:Serotonin; D013395:Sucrose; D020932:Nerve Growth Factor; D004298:Dopamine
5-Hydroxytryptamine (PubChem CID: 5202); Antidepressant; Baicalein (PubChem CID: 5281605); Baicalin (PubChem CID: 64982); CUMS; Dopamine (PubChem CID: 681); Ginsenoside Rg(1) (PubChem CID: 441923); Glycyrrhizic acid (PubChem CID: 14982); Isoliquiritin (PubChem CID: 5318591); Liquiritin (PubChem CID: 503737); Monoamine; Neurotrophin; Saikosaponin A (PubChem CID: 167928); Wogonin (PubChem CID: 5281703); Xiaochaihutang