title: Salvianolic acid B ameliorates depressive-like behaviors in chronic mild stress-treated mice: involvement of the neuroinflammatory pathway.
abstract: OBJECTIVE
  Major depressive disorder (MDD) is a debilitating mental disorder associated with dysfunction of the neurotransmitter-neuroendocrine system and neuroinflammatory responses. Salvianolic acid B (SalB) has shown a variety of pharmacological activities, including anti-inflammatory, antioxidant and neuroprotective effects. In this study, we examined whether SalB produced antidepressant-like actions in a chronic mild stress (CMS) mouse model, and explored the mechanisms underlying the antidepressant-like actions of SalB.
  
  
  METHODS
  Mice were subjected to a CMS paradigm for 6 weeks. In the last 3 weeks the mice were daily administered SalB (20 mg·kg(-1)·d(-1), ip) or a positive control drug imipramine (20 mg·kg(-1)·d(-1), ip). The depressant-like behaviors were evaluated using the sucrose preference test, the forced swimming test (FST), and the tail suspension test (TST). The gene expression of cytokines in the hippocampus and cortex was analyzed with RT-PCR. Plasma corticosterone (CORT) and cerebral cytokines levels were assayed with an ELISA kit. Neural apoptosis and microglial activation in brain tissues were detected using immunofluorescence staining.
  
  
  RESULTS
  Administration of SalB or imipramine reversed the reduced sucrose preference ratio of CMS-treated mice, and significantly decreased their immobility time in the FST and TST. Administration of SalB significantly decreased the expression of pro-inflammatory cytokines IL-1β and TNF-α, and markedly increased the expression of anti-inflammatory cytokines IL-10 and TGF-β in the hippocampus and cortex of CMS-treated mice, and normalized their elevated plasma CORT levels, whereas administration of imipramine did not significantly affect the imbalance between pro- and anti-inflammatory cytokines in the hippocampus and cortex of CMS-treated mice. Finally, administration of SalB significantly decreased CMS-induced apoptosis and microglia activation in the hippocampus and cortex, whereas administration of imipramine had no significant effect on CMS-induced apoptosis and microglia activation in the hippocampus and cortex.
  
  
  CONCLUSIONS
  SalB exerts potent antidepressant-like effects in CMS-induced mouse model of depression, which is associated with the inhibiting microglia-related apoptosis in the hippocampus and the cortex.
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
authors.forename: Jin-Qiang
authors.initials: JQ
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Wu
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
authors.affiliation: State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Xie
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Fan
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Yan
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
authors.forename: Qiu-Ying
authors.initials: QY
authors.lastname: Zhao
authors.affiliation: State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.affiliation: School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
authors.forename: Zi-Li
authors.initials: ZL
authors.lastname: You
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001572:Benzofurans / Q000008:administration & dosage / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000235:genetics; D003865:Major Depressive Disorder / Q000276:immunology / Q000517:prevention & control* / Q000523:psychology; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D015213:Neuroimmunomodulation / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D013315:Stress, Psychological / Q000188:drug therapy* / Q000276:immunology / Q000523:psychology; D053630:Depsides
chemical_list: D001572:Benzofurans; D003345:Corticosterone; D016207:Cytokines; D004365:Drugs, Chinese Herbal; C076944:salvianolic acid B; D053630:Depsides