Novel Botanical Therapeutic NB-02 Effectively Treats Alzheimer's Neuropathophysiology in an APP/PS1 Mouse Model

eNeuro. 2021 May 24;8(3):ENEURO.0389-20.2021. doi: 10.1523/ENEURO.0389-20.2021. Print 2021 May-Jun.

Abstract

Alzheimer's disease (AD) is an incurable neurodegenerative disorder and a major cause of dementia. Some of the hallmarks of AD include presence of amyloid plaques in brain parenchyma, calcium dysregulation within individual neurons, and neuroinflammation. A promising therapeutic would reverse or stymie these pathophysiologies in an animal model of AD. We tested the effect of NB-02, previously known as DA-9803, a novel multimodal therapeutic, on amyloid deposition, neuronal calcium regulation and neuroinflammation in 8- to 10-month-old APP/PS1 mice, an animal model of AD. In vivo multiphoton microscopy revealed that two-month-long administration of NB-02 halted amyloid plaque deposition and cleared amyloid in the cortex. Postmortem analysis verified NB-02-dependent decrease in plaque deposition in the cortex as well as hippocampus. Furthermore, drug treatment reversed neuronal calcium elevations, thus restoring neuronal function. Finally, NB-02 restored spine density and transformed the morphology of astrocytes as well as microglia to a more phagocytic state, affecting neuroinflammation. NB-02 was effective at reversing AD neuropathophysiology in an animal model. Therefore, in addition to serving as a promising preventative agent, NB-02 holds potential as a treatment for AD in the clinic.

Keywords: Alzheimer’s disease; astrocyte; neuron; therapy.

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Disease Models, Animal
  • Mice
  • Mice, Transgenic
  • Plaque, Amyloid / drug therapy

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor