Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Asiatic Acid Protects Dopaminergic Neurons from Neuroinflammation by Suppressing Mitochondrial ROS Production

  • Chen, Dong (Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University) ;
  • Zhang, Xiao-Ya (Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University) ;
  • Sun, Jing (Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University) ;
  • Cong, Qi-Jie (Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University) ;
  • Chen, Wei-Xiong (Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University) ;
  • Ahsan, Hafiz Muhammad (Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University) ;
  • Gao, Jing (Neurobiology & Mitochondrial Key Laboratory, School of Pharmacy, Jiangsu University) ;
  • Qian, Jin-Jun (Department of Neurology, The Fourth People's Hospital of Zhenjiang)
  • Received : 2018.09.27
  • Accepted : 2019.02.20
  • Published : 2019.09.01
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Abstract

This study sought to evaluate the effects of Asiatic acid in LPS-induced BV2 microglia cells and 1-methyl-4-phenyl-pyridine ($MPP^+$)-induced SH-SY5Y cells, to investigate the potential anti-inflammatory mechanisms of Asiatic acid in Parkinson's disease (PD). SH-SY5Y cells were induced using $MPP^+$ to establish as an in vitro model of PD, so that the effects of Asiatic acid on dopaminergic neurons could be examined. The NLRP3 inflammasome was activated in BV2 microglia cells to explore potential mechanisms for the neuroprotective effects of Asiatic acid. We showed that Asiatic acid reduced intracellular production of mitochondrial reactive oxygen species and altered the mitochondrial membrane potential to regulate mitochondrial dysfunction, and suppressed the NLRP3 inflammasome in microglia cells. We additionally found that treatment with Asiatic acid directly improved SH-SY5Y cell viability and mitochondrial dysfunction induced by $MPP^+$. These data demonstrate that Asiatic acid both inhibits the activation of the NLRP3 inflammasome by downregulating mitochondrial reactive oxygen species directly to protect dopaminergic neurons from, and improves mitochondrial dysfunction in SH-SY5Y cells, which were established as a model of Parkinson's disease. Our finding reveals that Asiatic acid protects dopaminergic neurons from neuroinflammation by suppressing NLRP3 inflammasome activation in microglia cells as well as protecting dopaminergic neurons directly. This suggests a promising clinical use of Asiatic acid for PD therapy.

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References

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