Protective Effects of Withania Somnifera Extract in SOD1 G93A Mouse Model of Amyotrophic Lateral Sclerosis

Exp Neurol. 2018 Nov;309:193-204. doi: 10.1016/j.expneurol.2018.08.008. Epub 2018 Aug 19.

Abstract

Withania somnifera (WS; commonly known as Ashwagandha or Indian ginseng) is a medicinal plant whose extracts have been in use for centuries in various regions of the world as a rejuvenator. There is now a growing body of evidence documenting neuroprotective functions of the plant extracts or its purified compounds in several models of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Based on the extract's beneficial effect in a mouse model of ALS with TDP-43 proteinopathy, the current study was designed to test its efficacy in another model of familial ALS. Our results show that administration of WS extracts by gavage to mice expressing G93A mutant form of superoxide dismutase (SOD1) resulted in increased longevity, improved motor performance and increased number of motor neurons in lumbar spinal cord. The WS treatment caused substantial reduction in levels of misfolded SOD1whereas it enhanced expression of cellular chaperons in spinal cord of SOD1G93A mice. WS markedly reduced glial activation and prevented phosphorylation of nuclear factor kappaB (NF-κB). The overall immunomodulatory effect of WS was further evidenced by changes in expression of multiple cytokines/chemokines. WS also served as an autophagy inducer which may be beneficial at early stages of the disease. These results suggest that WS extracts might constitute promising therapeutics for treatment of ALS with involvement of misfolded SOD1.

Keywords: Amyotrophic lateral sclerosis; Autophagy; SOD1; Withania somnifera.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Autophagy / drug effects
  • Body Weight / drug effects
  • Body Weight / genetics
  • Calcium-Binding Proteins / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Ganglia, Spinal / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microfilament Proteins / metabolism
  • Motor Neurons / drug effects
  • Nerve Tissue Proteins / metabolism
  • Neuroprotective Agents / therapeutic use*
  • Plant Extracts / therapeutic use*
  • Psychomotor Performance / drug effects
  • Reflex / drug effects
  • Reflex / genetics
  • Spinal Cord / pathology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Withania / chemistry*

Substances

  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Cytokines
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Plant Extracts
  • SOD1 G93A protein
  • Superoxide Dismutase

Grant support