title: Glucocorticoid receptor is involved in the neuroprotective effect of ginsenoside Rg1 against inflammation-induced dopaminergic neuronal degeneration in substantia nigra.
abstract: Accumulating clinical and experimental evidence suggests that chronic neuroinflammation is associated with dopaminergic neuronal death in Parkinson's disease (PD). Ginsenoside Rg1, the most active components of ginseng, possesses a variety of biological effects on the central nervous system, cardiovascular system and immune system. The present study aimed to evaluate the protective effects of ginsenoside Rg1 on lipopolysaccharide (LPS)-induced microglia activation and dopaminergic neuronal degeneration in rat substantia nigra (SN) and its potential mechanisms. Treatment with Rg1 could ameliorate the apomorphine-induced rotational behavior in LPS-lesioned rats. GR antagonist RU486 partly abolished the protective effect of Rg1. Rg1 treatment significantly attenuated LPS-induced loss of tyrosin hydroxlase (TH) positive neurons in substantial nigra par compacta (SNpc) and decreased content of dopamine (DA) and its metabolites in striatum of the lesioned side. Meanwhile, Rg1 significantly inhibited LPS-induced microglial activation and production of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and nitric oxide (NO). These effects were abolished by co-treatment with RU486. In addition, Rg1 treatment significantly inhibited the LPS-induced phosphorylation of IκB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) in the lesioned side of substantial nigra. These effect could be also partly blocked by RU486. Taken together, these data indicate that Rg1 has protective effects on mesencephalic dopaminergic neurons from LPS-induced microglia inflammation. GR signaling pathway might be involved in the anti-inflammatory effect of Rg1.
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Medical College of Qingdao University, Qingdao, PR China; Department of Special Medicine, Medical College of Qingdao University, Qingdao, People's Republic of China; Department of Physiology, Medical College of Taishan, Taian, People's Republic of China.
authors.forename: Xian-Chang
authors.initials: XC
authors.lastname: Sun
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Medical College of Qingdao University, Qingdao, PR China; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, People's Republic of China.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Ren
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Medical College of Qingdao University, Qingdao, PR China; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Medical College of Qingdao University, Qingdao, PR China; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, People's Republic of China.
authors.forename: Xian-Qi
authors.initials: XQ
authors.lastname: Gao
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Medical College of Qingdao University, Qingdao, PR China; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, People's Republic of China.
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Xie
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Medical College of Qingdao University, Qingdao, PR China; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, People's Republic of China. Electronic address: chenwenfangqd@163.com.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Chen
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D036145:Ginsenosides / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D036145:Ginsenosides; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D015735:Mifepristone; D001058:Apomorphine; C035054:ginsenoside Rg1; D004298:Dopamine
keywords: Dopaminergic neuron; Ginsenoside Rg1; Glucocorticoid receptor; LPS; Neuroinflammation; Parkinson’s disease