title: Analysis of main constituents and mechanisms underlying antidepressant-like effects of Xiaochaihutang in mice.
abstract: BACKGROUND
  Xiaochaihutang (XCHT), a famous Chinese herbal formula which consists of seven Chinese herbs, has been used clinically in depressive disorders in China. Our previous studies have demonstrated that XCHT improved depressive-like behavior in several animal models of depression. However, therapeutic basis of XCHT on depression are challenging, due to the complex active constituents of XCHT and the unclear pharmacological mechanism of action.
  
  
  METHODS
  To provide further insights into therapeutic basis of XCHT, the core in compatibility of XCHT on antidepressant therapy was assessed by the method of orthogonal array design. The comparative evaluations on antidepressant effects of XCHT and its core in compatibility were executed by tail suspension test (TST), forced swim test (FST), novelty suppressed feeding test (NSFT), reserpine-induced hypothermia and palpebral ptosis. Moreover, the potential mechanism was explored by investigating levels of monoamine neurotransmitters in hypothalamus and striatum and neurogenesis in hippocampus. Chemical profile of active constituents in plasma after oral administration of the core in compatibility of XCHT was revealed by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
  
  
  RESULTS
  The results of orthogonal array design experiment showed that Huangqin (Radix scutellariae), Renshen (Ginseng) and Gancao (Radix glycyrrhizae), defined as HRG, might be the core in compatibility of XCHT on antidepressant therapy. In accordance with XCHT, oral administration of HRG for 15 days significantly reduced immobility duration in TST and FST without affecting locomotor activity. Both HRG and XCHT increased immobility latency in FST, decreased the latency in NSFT, reversed reserpine-induced hypothermia and palpebral ptosis. Moreover, both HRG and XCHT significantly increased levels of 5-HT and DA in hypothalamus. In addition, HRG could remarkably increase Ki-67 and doublecortin (DCX) positive cells in hippocampus. A total 25 active constituents in plasma, including 14 prototype components and 11 metabolites, were identified by UPLC-MS/MS after oral administration of HRG.
  
  
  CONCLUSIONS
  The present results reveal that HRG is supposed to be the core in compatibility of XCHT on antidepressant therapy. In accordance with XCHT, HRG exerts significant antidepressant-like effects, which are likely attributed to regulating serotonergic and dopaminergic systems and increasing hippocampal neurogenesis. The constituents identified in plasma after oral administration of HRG may be the potential active ingredients for the treatment of depression.
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors: Kuo
authors: K
authors: Zhang
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors: Fang
authors: F
authors: Wang
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors: Jing-yu
authors: JY
authors: Yang
authors: Department of Pharmaceutical Analysis, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors: Li-juan
authors: LJ
authors: Wang
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors: Huan-huan
authors: HH
authors: Pang
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors: Guang-yue
authors: GY
authors: Su
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors: Jie
authors: J
authors: Ma
authors: Department of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors: Shao-jiang
authors: SJ
authors: Song
authors: Department of Pharmaceutical Analysis, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: bearry200@126.com.
authors: Zhi-li
authors: ZL
authors: Xiong
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China. Electronic address: wucf@syphu.edu.cn.
authors: Chun-fu
authors: CF
authors: Wu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000089662:Doublecortin Protein; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D005248:Feeding Methods; D006035:Glycyrrhiza; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D005894:Panax; D031364:Scutellaria baicalensis; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D015306:Biogenic Monoamines; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D004365:Drugs, Chinese Herbal; C461320:shosaiko-to
keywords: 3,4-Dihydroxyphenylacetic acid (PubChem CID: 547); 4-Hydroxy-3-methoxyphenylacetic acid (PubChem CID: 1738); 5-Hydroxyindole-3-acetic acid (PubChem CID: 1826).; 5-Hydroxytryptamine (PubChem CID: 5202); Active constituents; Antidepressant; Baicalein (PubChem CID: 5281605); Baicalin (PubChem CID: 64982); Behavioral test; Compatibility; Dopamine (PubChem CID: 681); Liquiritin (PubChem CID: 503737); Monoamine neurotransmitter; Wogonin (PubChem CID: 5281703); Wogonoside (PubChem CID: 29927693); Xiaochaihutang