Salvianolic acid B ameliorates depressive-like behaviors in chronic mild stress-treated mice： involvement of the neuroinflammatory pathway  

作　　者：Jin-qiang ZHANG Xiao-hui WU Yi FENG Xiao-fang XIE Yong-hua FAN Shuo YAN Qiu-ying ZHAO Cheng PENG Zi-li YOU 

机构地区：[1]School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China [2]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

出　　处：《Acta Pharmacologica Sinica》2016年第9期1141-1153,共13页中国药理学报（英文版）

摘　　要：Aim： 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-IO 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 sigAim： 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-IO 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 sig

关 键 词：major depressive disorder chronic mild stress ANTIDEPRESSANT salvianolic acid B IMIPRAMINE CYTOKINES apoptosis microglia activation 

分 类 号：R[医药卫生]