Biomol Ther.  2019 Sep;27(5):442-449. 10.4062/biomolther.2018.188.

Asiatic Acid Protects Dopaminergic Neurons from Neuroinflammation by Suppressing Mitochondrial ROS Production

• Chen D
• Zhang XY
• Sun J
• Cong QJ
• Chen WX
• Ahsan HM
• Gao J
• Qian JJ

• KMID: 2456218
• DOI: http://doi.org/10.4062/biomolther.2018.188

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.

Keyword

Parkinson’s disease; Neuroinflammation; Asiatic acid; NLRP3 inflammasome; Mitochondria

MeSH Terms

Cell Survival
Dopaminergic Neurons*
In Vitro Techniques
Inflammasomes
Membrane Potential, Mitochondrial
Microglia
Mitochondria
Neuroprotective Agents
Reactive Oxygen Species
Inflammasomes
Neuroprotective Agents
Reactive Oxygen Species