Glucocorticoid receptor is involved in the neuroprotective effect of ginsenoside Rg1 against inflammation-induced dopaminergic neuronal degeneration in substantia nigra.
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.
['Sun|Xian-Chang|XC|', 'Ren|Xiao-Fan|XF|', 'Chen|Lei|L|', 'Gao|Xian-Qi|XQ|', 'Xie|Jun-Xia|JX|', 'Chen|Wen-Fang|WF|']
D000818:Animals D001058:Apomorphine D004298:Dopamine D005260:Female D036145:Ginsenosides D007249:Inflammation D008070:Lipopolysaccharides D017628:Microglia D015735:Mifepristone D009474:Neurons D018696:Neuroprotective Agents D009569:Nitric Oxide D017208:Rats, Wistar D011965:Receptors, Glucocorticoid D013378:Substantia Nigra D014409:Tumor Necrosis Factor-alpha
Glucocorticoid receptor Ginsenoside Rg1 Dopaminergic neuron Neuroinflammation LPS Parkinson’s disease