Astragaloside IV and echinacoside benefit neuronal properties via direct effects and through upregulation of SOD1 astrocyte function in vitro

Naunyn Schmiedebergs Arch Pharmacol. 2021 May;394(5):1019-1029. doi: 10.1007/s00210-020-02022-w. Epub 2020 Nov 20.

Abstract

Amyotrophic lateral sclerosis (ALS), also known as a major type of motor neuron disease, is a disease characterized by the degeneration of both upper and lower motor neurons. Astragaloside IV (AST) is one of the most effective compounds isolated from Astragalus membranaceus. Echinacoside (ECH) is also an active constituent in Cistanche tubulosa. These two herbs had been used in treating disease described like ALS in ancient China under the guidance of traditional Chinese medicine theory and now they are still being used extensively for ALS in current Chinese medicine practice, but whether AST or ECH has effect on ALS disease condition is still unclear. Survivals of primary cultured neuron and astrocyte were determined by the MTS assay. Proteins including GLT1 and GFAP, from SOD1 G93A Tg (transgenic) astrocyte lysate were determined by Western blot. Synaptic markers, PSD95 and VGLUT1, were stained by immunofluorescence and observed by a confocal microscope. Proper dilution of AST and ECH was confirmed to be not harmful to both astrocytes and neurons. AST and ECH enhanced neuronal synaptic markers density or intensity/area in different aspects. Both AST and ECH could significantly rescue SOD1 astrocyte conditional medium-treated neuronal survival and synapse loss. Ten micromolars ECH could significantly rescue the suppressed GLT1 level expressed by SOD1 Tg astrocyte. This present research proved that AST and ECH could benefit neuronal properties and rescue certain dysfunction, such as GLT1 low expression, loss of neuron-supporting function, of astrocytes under SOD1 condition.

Keywords: ALS; Astragaloside IV; Echinacoside; GLT1; Neuronal properties; SOD1.

Publication types

  • Comparative Study

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Astragalus propinquus / chemistry
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Cistanche / chemistry
  • Disease Models, Animal
  • Excitatory Amino Acid Transporter 2 / metabolism
  • Glycosides / isolation & purification
  • Glycosides / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism
  • Saponins / isolation & purification
  • Saponins / pharmacology*
  • Superoxide Dismutase-1 / metabolism
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*
  • Up-Regulation / drug effects

Substances

  • Excitatory Amino Acid Transporter 2
  • Glycosides
  • Saponins
  • Slc1a2 protein, mouse
  • Triterpenes
  • astragaloside A
  • Sod1 protein, mouse
  • Superoxide Dismutase-1
  • echinacoside