The effect of Chaihu-Shugan-San and its components on the expression of ERK5 in the hippocampus of depressed rats.
BACKGROUND
Chaihu-Shugan-San (CSS) is a well-known, Chinese traditional medicine used to treat depression. Little is known about the antidepressant mechanism of CSS. The main aims of the this study were to evaluate the antidepressant-like effects of CSS and its components and further explore the CSS׳s effect upon signal transduction of extracellular signal-regulated kinase 5 (ERK5) expressions in the hippocampus of rats with depression induced by chronic unpredicted mild stress.


METHODS
SD rats were randomly divided into six groups: Normal; Model; CSS; Component I; Component II; and Fluoxetine. Antidepressant-like effects of CSS and two of its constituents, Components I and II in aqueous extract, were assessed using rats exposed to chronic unpredictable mild stress (CUMS) by measuring weight change, observing the open-field test and measuring sucrose water consumption. Antidepressant mechanism were examined by measuring the effect of CSS, and two of its constituents, on extracellular signal-regulated kinase 5 (ERK5) expression, phosphorylation-ERK5 (p-ERK5), and ERK5 mRNA in the hippocampus by using western blotting and Real-time Polymerase Chain Reaction (PCR). Three preparations were prepared: (1) an aqueous extract of CSS (5.9 g/kg·d); (2) Component I (3.3 g/kg·d); and (3) Component II (2.6 g/kg·d). During the 28-day CUMS, the three preparations were intragastrically administered all three preparations. Simultaneously a parallel positive fluoxetine control group was given fluoxetine hydrochloride (1.8mg/kg·d). Normal and Model groups were intragastrically administered with a isovolumic distilled water (4.5 ml/kg·d).


RESULTS
Depressed rats had decreased weight gain; decreased locomotor activity as measured by the open field test; and reduced sucrose consumption. The rats׳ hippocampus ERK5 activation was significantly suppressed. CSS reduced the incidence of depressive-like behaviors and increased ERK5 activation in depressed rats at the same rate as fluoxetine. Component I, and II, each had only a partial effect on the depression indicators measured.


CONCLUSIONS
CSS aqueous extract has antidepressant-like effects on CUMS-induced depression model rats. The antidepressant effect of CSS is greater than that of either the two separate components measured. CSS׳s antidepressant mechanism may be mediated by reversing the stress-induced disruption of ERK5 activity.
Institute of Integrated Traditional Chinese Medicine and Western Medicine, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan, China; Department of Nuclear Medicine, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China. Electronic address: tangzl@163.com.
Juan
J
Qiu
Institute of Integrated Traditional Chinese Medicine and Western Medicine, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan, China.
Sui-Yu
SY
Hu
Institute of Integrated Traditional Chinese Medicine and Western Medicine, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan, China.
Chun-Hu
CH
Zhang
Department of Nuclear Medicine, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Guang-Qing
GQ
Shi
Institute of Integrated Traditional Chinese Medicine and Western Medicine, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan, China.
Su-e
SE
Wang
Department of Nuclear Medicine, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Tian
T
Xiang
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics*; D009043:Motor Activity / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
D000928:Antidepressive Agents; D010936:Plant Extracts; C497000:chaihu-shugan-san; D005473:Fluoxetine; D048054:Mitogen-Activated Protein Kinase 7
Antidepressant-like activity; Chaihu-Shugan-San; Extracellular signal-regulated kinase; Hippocampus