Astragaloside IV ameliorates motor deficits and dopaminergic neuron degeneration via inhibiting neuroinflammation and oxidative stress in a Parkinson's disease mouse model

• Published in: International immunopharmacology 2019-10, Vol.75, p.105651-105651, Article 105651
• Main Authors: Yang, Cong, Mo, Yousheng, Xu, Erjin, Wen, Huihong, Wei, Renrong, Li, Shaoling, Zheng, Jiayi, Li, Weirong, Le, Baoluu, Chen, Yonggen, Pan, Huafeng, Huang, Shuiqing, Wang, Shengqiang, Wang, Qi
• Format: Article
• Language: English
• Subjects: Activation; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants; Astragaloside IV; Astragalus membranaceus; Cell Line; Degeneration; Disease Models, Animal; Dopamine receptors; Dopaminergic Neurons - drug effects; Inflammasomes; Inflammasomes - immunology; Inflammation; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Male; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Microglia - immunology; Molecular modelling; Motor Activity - drug effects; Movement disorders; MPTP; MPTP Poisoning - drug therapy; MPTP Poisoning - immunology; MPTP Poisoning - physiopathology; Neurodegeneration; Neurodegenerative diseases; Neuroinflammation; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; NF-E2-Related Factor 2; NF-κB protein; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors; NLR Family, Pyrin Domain-Containing 3 Protein - immunology; NLRP3; Nrf2; Oxidative stress; Oxidative Stress - drug effects; Parkinson's disease; Rats; Reactive oxygen species; Saponins - pharmacology; Saponins - therapeutic use; Signal transduction; Triterpenes - pharmacology; Triterpenes - therapeutic use
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.05.036

Oxidative stress and neuroinflammation are the key and early events during the pathological process of Parkinson's disease (PD). Thus, therapeutic intervention to regulate oxidative stress and neuroinflammation would be an effective strategy to alleviate the progression of PD. Astragaloside IV, the main active component isolated from Astragalus membranaceus, has been shown to possess anti-inflammatory and anti-oxidant properties in neurodegeneration diseases, however, the molecular mechanisms of Astragaloside IV in the pathology of PD are still unclear. In this study, we explored the mechanisms of Astragaloside IV of PD on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model and lipopolysaccharide (LPS)-induced BV2 microglia cells. Our results showed Astragaloside IV significantly alleviated behavioral impairments and dopaminergic neuron degeneration induced by MPTP. Also, Astragaloside IV inhibited microglia activation and reduced the oxidative stress of MPTP mouse model. In addition, Astragaloside IV significantly inhibited NFκB mediated NLRP3 inflammasome activation and activated Nrf2 both in vivo and in vitro. Furthermore, Astragaloside IV lessened reactive oxygen species (ROS) generation in LPS-induced BV2 microglia cells remarkably. These findings demonstrate that Astragaloside IV protects dopaminergic neuron from neuroinflammation and oxidative stress which are largely dependent upon activation of the Nrf2 pathways and suppression of NFκB/NLRP3 inflammasome signaling pathway. Therefore, Astragaloside IV is a promising neuroprotective agent that should be further developed for neurodegeneration diseases. •Astragaloside IV could protect the dopaminergic neuron from neuroinflammation and oxidative stress.•The neuroprotective effect of Astragaloside IV on PD may be through the promotion of Nrf2 activation and inhibition of NLRP3 inflammasome activation.•Astragaloside IV might be the therapeutic drug for PD treatment.