title: Salvianolic acid B attenuates toxin-induced neuronal damage via Nrf2-dependent glial cells-mediated protective activity in Parkinson's disease models.
abstract: Salvianolic acid B (SalB), a bioactive compound isolated from the plant-derived medicinal herb Danshen, has been shown to exert various anti-oxidative and anti-inflammatory activities in several neurological disorders. In this study, we sought to investigate the potential protective effects and associated molecular mechanisms of SalB in Parkinson's disease (PD) models. To determine the neuroprotective effects of SalB in vitro, MPP+- or lipopolysaccharide (LPS)-induced neuronal injury was achieved using primary cultures with different compositions of neurons, microglia and astrocytes. Our results showed that SalB reduced both LPS- and MPP+-induced toxicity of dopamine neurons in a dose-dependent manner. Additionally, SalB treatment inhibited the release of microglial pro-inflammatory cytokines and resulted in an increase in the expression and release of glial cell line-derived neurotrophic factor (GDNF) from astrocytes. Western blot analysis illustrated that SalB increased the expression and nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The knockdown of Nrf2 using specific small interfering RNA (siRNA) partially reversed the SalB-induced GDNF expression and anti-inflammatory activity. Moreover, SalB treatment significantly attenuated dopaminergic (DA) neuronal loss, inhibited neuroinflammation, increased GDNF expression and improved the neurological function in MPTP-treated mice. Collectively, these findings demonstrated that SalB protects DA neurons by an Nrf-2 -mediated dual action: reducing microglia activation-mediated neuroinflammation and inducing astrocyte activation-dependent GDNF expression. Importantly the present study also highlights critical roles of glial cells as targets for developing new strategies to alter the progression of neurodegenerative disorders.
authors.affiliation: Department of Neurosurgery, Lanzhou General Hospital, Lanzhou Command of PLA, Lanzhou, Gansu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Lanzhou General Hospital, Lanzhou Command of PLA, Lanzhou, Gansu, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Qu
authors.affiliation: Department of Neurosurgery, Lanzhou General Hospital, Lanzhou Command of PLA, Lanzhou, Gansu, China.
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Lanzhou General Hospital, Lanzhou Command of PLA, Lanzhou, Gansu, China.
authors.lastname: Wei-Ji
authors.affiliation: Department of Neurosurgery, Lanzhou General Hospital, Lanzhou Command of PLA, Lanzhou, Gansu, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Lanzhou General Hospital, Lanzhou Command of PLA, Lanzhou, Gansu, China.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Lanzhou General Hospital, Lanzhou Command of PLA, Lanzhou, Gansu, China.
authors.forename: Jiao-Jiang
authors.initials: JJ
authors.lastname: He
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001572:Benzofurans / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053630:Depsides
chemical_list: D015655:1-Methyl-4-phenylpyridinium; D001572:Benzofurans; D016207:Cytokines; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; C495040:Gdnf protein, mouse; C495636:Nfe2l2 protein, mouse; C076944:salvianolic acid B; D053630:Depsides