DA-9805 protects dopaminergic neurons from endoplasmic reticulum stress and inflammation

Sora Kang, Ying Piao, Young Cheol Kang, Suyeol Lim, Youngmi Kim Pak

Research output: Contribution to journalArticlepeer-review

Abstract

Parkinson's disease (PD) is a multifactorial neurodegenerative disease with damages to mitochondria and endoplasmic reticulum (ER), followed by neuroinflammation. We previously reported that a triple herbal extract DA-9805 in experimental PD toxin-models had neuroprotective effects by alleviating mitochondrial damage and oxidative stress. In the present study, we investigated whether DA-9805 could suppress ER stress and neuroinflammation in vitro and/or in vivo. Pre-treatment with DA-9805 (1 μg/ml) attenuated upregulation of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and cleaved caspase-3 in SH-SY5Y neuroblastoma cells treated with thapsigargin (1 µg/ml) or tunicamycin (2 µg/ml). In addition, DA-9805 prevented the production of IL-1β, IL-6, TNF-α and nitric oxide through inhibition of NF-κB activation in BV2 microglial cells stimulated with lipopolysaccharides (LPS). Intraperitoneal injection of LPS (10 mg/kg) into mice can induce acute neuroinflammation and dopaminergic neuronal cell death. Oral administration of DA-9805 (10 or 30 mg/kg/day for 3 days before LPS injection) prevented loss of dopaminergic neurons and activation of microglia and astrocytes in the substantia nigra in LPS-injected mouse models. Taken together, these results indicate that DA-9805 can effectively prevent ER stress and neuroinflammation, suggesting that DA-9805 is a multitargeting and disease-modifying therapeutic candidate for PD.

Original languageEnglish
Article number112389
JournalBiomedicine and Pharmacotherapy
Volume145
DOIs
Publication statusPublished - Jan 2022

Keywords

  • ER stress
  • Herbal medicine
  • Mitochondria
  • Neuroinflammation
  • Parkinson's disease

Fingerprint

Dive into the research topics of 'DA-9805 protects dopaminergic neurons from endoplasmic reticulum stress and inflammation'. Together they form a unique fingerprint.

Cite this