Parkinson�s disease (PD) was one of the most common neurodegenerative diseases with a slow and progressive loss of dopamine\n(DA) neurons in the midbrain substantia nigra (SN). Neuroinflammation was identified to be an important contributor to PD\npathogenesis with the hallmark of microglia activation. Tetrahydroxystilbene glucoside (TSG) was the main active component\nextracted from Polygonum multiflorum and held amounts of pharmacological activities including antioxidant, free radicalscavenging,\nanti-inflammation, and cardioprotective properties. Recent studies demonstrated that TSG exerted neuroprotection\nfrom several neurodegenerative disease models. However, the underlying mechanisms were not completely elucidated. In the\npresent study, rat nigral stereotaxic injection of 6-hydroxydopamine- (6-OHDA-) elicited DA neuronal injury was performed to\ninvestigate TSG-mediated neuroprotection on DA neurons. In addition, primary rat midbrain neuron-glia cocultures were\napplied to explore the mechanisms underlying TSG-exerted neuroprotection. Results showed that daily intraperitoneal injection\nof TSG for 14 consecutive days significantly protected DA neurons from 6-OHDA-induced neurotoxicity and suppressed\nmicroglia activation. Similar neuroprotection was shown in primary neuron-glia cocultures. In vitro studies further\ndemonstrated that TSG inhibited microglia activation and subsequent release of proinflammatory factors. Moreover, TSGmediated\nneuroprotection was closely related with the inactivation of mitogen-activated protein kinase (MAPK) signaling\npathway. Together, TSG protects DA neurons from 6-OHDA-induced neurotoxicity via the inhibition of microglia-elicited\nneuroinflammation. These findings suggest that TSG might hold potential therapeutic effects on PD.
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