Berberine attenuates Aβ-induced neuronal damage through regulating miR-188/NOS1 in Alzheimer's disease

Mol Cell Biochem. 2020 Nov;474(1-2):285-294. doi: 10.1007/s11010-020-03852-1. Epub 2020 Aug 10.

Abstract

Alzheimer's disease (AD) is a public health issue worldwide. Berberine (Ber) acts as the neuroprotective role in an animal experiment of AD. MicroRNA-188 (miRNA-188) was reported to be decreased in primary hippocampal neurons of mice. However, the roles and molecular basis of Ber and miRNA-188 in the treatment of AD need to be further explored. In this study, 5 μM Ber treatment has little effect on cell viability. Ber treatment or miR-188 overexpression expedited proliferation and inhibited caspase-3 activity and apoptotic rate in amyloid-beta (Aβ)-treated BV2 and N2a cells. MiR-188 was downregulated, and nitric oxide synthase 1 (NOS1) was upregulated in Aβ-induced BV2 and N2a cells. NOS1 worked as the target of miR-188. NOS1 overturned miR-188-induced effects on cell viability, caspase-3 activity, and apoptotic rate in Aβ-induced BV2 and N2a cells. Ber mitigated neuronal damage in Aβ-induced BV2 and N2a cells by miR-188/NOS1 axis. These results suggested that Ber accelerated cell viability and suppressed caspase-3 activity and apoptotic rate possible by miR-188/NOS1 pathway, implying the treatment of Ber as an underlying effective drug for AD patients.

Keywords: Alzheimer’s disease; Apoptosis; Ber; NOS1; Proliferation; miR-188.

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / prevention & control
  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Berberine / pharmacology*
  • Cells, Cultured
  • Gene Expression Regulation
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Microglia / drug effects*
  • Microglia / metabolism
  • Microglia / pathology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide Synthase Type I / genetics
  • Nitric Oxide Synthase Type I / metabolism*
  • Signal Transduction

Substances

  • Amyloid beta-Peptides
  • MIRN188 microRNA, mouse
  • MicroRNAs
  • Neuroprotective Agents
  • Berberine
  • Nitric Oxide Synthase Type I
  • Nos1 protein, mouse