title: Antidepressant-like effect of ethanol extract from Zuojin Pill, containing two herbal drugs of Rhizoma Coptidis and Fructus Evodiae, is explained by modulating the monoaminergic neurotransmitter system in mice.
abstract: BACKGROUND
  Zuojin Pill (ZJP), a traditional Chinese medicinal decoction, contains two herbal drugs: Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in the ratio of 6:1 (w/w). Previous pharmacological studies have shown that two herbs in ZJP have the antagonistic effects on catecholamine secretion in bovine adrenal medullary cells. Furthermore, the alkaloids from the two herbs in ZJP may provide a protective effect for depression in individuals with a low expressing 5-HTT allele by increasing receptor concentration in serotonergic neurons. However, antidepressant effect has not been reported before and has not been fully clarified.
  
  
  OBJECTIVE
  The present study aimed to investigate the antidepressant potential of ethanol extract from ZJP and its monoaminergic mechanism in mice.
  
  
  METHODS
  Seven alkaloids were determined from the ethanol extract of ZJP using High Performance Liquid Chromatography (HPLC) with the gradient mobile phase. The ethanol extract from ZJP was used to evaluate the antidepressant potential in mice. Mouse models of depression including the tail suspension test (TST) and the forced swim test (FST) were used to evaluate the effects of the ethanol extract from ZJP. A possible mechanism was explored in the tests of antagonism of reserpine-induced ptosis and hypothermia, and 5-HTP induced head twitch response in mice. The contents of monoamine neurotransmitters including norepinephrine (NE), serotonin (5-hydroxytryptamine or 5-HT) in hippocampus of mice and NE, 5-HT, dopamine (DA) in striatum of mice were determined by HPLC system with Electrochemical Detector (ECD).
  
  
  RESULTS
  The results showed that intragastric administration of the ethanol extract from ZJP (5, 10, 20mg/kg) or fluoxetine (7.5mg/kg) significantly reduced the duration of immobility in TST and FST. However, the effect was not dose-dependent. Ethanol extract from ZJP (5, 10, 20mg/kg) also increased the accumulative number of the 5-HTP-induced head twitch response in mice. The mice were treated with the ethanol extract from ZJP (5, 10, 20mg/kg) or fluoxetine (7.5mg/kg), which could antagonize reserpine-induced ptosis and hypothermia, moreover, both of them could elevate the contents of NE, 5-HT in hippocampus as well as NE, 5-HT, DA in striatum significantly.
  
  
  CONCLUSIONS
  These results indicate that the ethanol extract from ZJP produced antidepressant-like effect and the possible mechanism, at least in part, is via the central monoaminergic neurotransmitter system and 5-HT plays a major role.
authors.affiliation: Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88 YuQuan Road, Nankai District, Tianjin 300193, PR China.
authors.forename: Qiang-Song
authors.initials: QS
authors.lastname: Wang
authors.forename: Shi-Lan
authors.initials: SL
authors.lastname: Ding
authors.forename: Hao-Ping
authors.initials: HP
authors.lastname: Mao
authors.forename: Yuan-Lu
authors.initials: YL
authors.lastname: Cui
authors.forename: Xue-Jie
authors.initials: XJ
authors.lastname: Qi
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D039323:Coptis / Q000737:chemistry*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D000431:Ethanol / Q000737:chemistry; D032086:Evodia / Q000737:chemistry*; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism*; D008517:Phytotherapy / Q000379:methods; D011897:Random Allocation; D012110:Reserpine / Q000494:pharmacology; D027343:Rhizome / Q000737:chemistry*; D012701:Serotonin / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D004365:Drugs, Chinese Herbal; D018377:Neurotransmitter Agents; C545320:zuojin; D005473:Fluoxetine; D012701:Serotonin; D000431:Ethanol; D012110:Reserpine; D006916:5-Hydroxytryptophan; D004298:Dopamine