title: Chinese herbal medicines promote hippocampal neuroproliferation, reduce stress hormone levels, inhibit apoptosis, and improve behavior in chronically stressed mice.
abstract: BACKGROUND
  An efficacious antidepressant without unwanted side effects is need urgently at present. This study aimed to investigate whether treatment with four Chinese herbal medicines (CHMs), namely Radix Astragali, Saposhnikovia divaricate (SD), Eucommia ulmoides Oliv. bark (EU), and Corydalis yanhusuo W. T. Wang (C. yanhusuo), could reverse the effects of chronic mild stress (CMS) in a depression-like mouse model and the potential mechanism(s) of their action.
  
  
  METHODS
  In vitro study, the proliferation of NSCs was assessed using the MTS assay. In vivo study, chronic mild stress (CMS) was used in mice for 14 days to establish a depression-like mouse model. Plasma corticosterone levels were assessed by UPLC coupled to a triple-quadrupole mass spectrometer. The forced swim test (FST) was used to assess the effects of the four CHMs on depression. BrdU incorporation and TUNEL staining were used to assay hippocampal precursor cell proliferation rate and apoptosis.
  
  
  RESULTS
  The CHMs included Radix Astragali, EU, C. yanhusuo, and SD were shown to promote neuroproliferation in vitro. In vivo study, oral administration of these four CHMs for 14 days reversed the elevated plasma corticosterone levels, body weight loss, decrease in proliferation of hippocampal precursor cells; they also inhibited hippocampal cell apoptosis, and exhibited an antidepressant-like effect in a depression-like mouse model induced by CMS.
  
  
  CONCLUSIONS
  Our study indicates that each of these CHMs has the potential to ameliorate depression. The possible mechanisms of action include modulation of the HPA axis, reduction in stress hormone levels, inhibition of apoptosis, and promotion of hippocampal neuronal plasticity and neurogenesis.
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Gao-Ge
authors.initials: GG
authors.lastname: Sun
authors.affiliation: Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Jui-Hu
authors.initials: JH
authors.lastname: Shih
authors.affiliation: Institute of Pharmacology, National Yang-Ming University & Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital & School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Chen-Jee
authors.initials: CJ
authors.lastname: Hong
authors.affiliation: Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Shao-Wei
authors.initials: SW
authors.lastname: Lu
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China; Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China. Electronic address: paolh@mail.cgust.edu.tw.
authors.forename: Li-Heng
authors.initials: LH
authors.lastname: Pao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood*; D003863:Depression / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D004365:Drugs, Chinese Herbal; D003345:Corticosterone
keywords: Anti-depression; Chinese herbal medicine; Hippocampus; Neural stem cell; Neurogenesis