Treatment with extracts from the Withania somnifera plant improved motor performance and delayed disease progression in mice with amyotrophic lateral sclerosis (ALS), according to researchers.
The study, “Protective effects of Withania somnifera extract in SOD1G93A mouse model of amyotrophic lateral sclerosis,” was published in the journal Experimental Neurology.
ALS generally develops sporadically, indicating that in most cases, there is no definitive cause or inheritance pattern. However, 10% of patients with ALS develop the disease due to inherited mutations, known as familial ALS (fALS).
Mutations that occur in the SOD1 gene account for approximately 20% of all familial ALS cases and 2-7% of sporadic cases. The mutant SOD1 gene provides instructions to produce abnormal SOD1 protein.
Studies suggest that, in the cases associated with these mutations, ALS develops as the mutant SOD1 proteins fold incorrectly and form aggregates, leading to cellular stress, dysfunction of the mitochondria (the cellular organelle that is responsible for producing energy), and issues with nerve cell function.
Withania somnifera, an herb whose extracts have long been used in Indian, Chinese, and Arabic traditional medicines, has been reported to possess a broad range of effects, including anti-inflammatory, anti-tumor, anti-oxidant, and rejuvenating properties.
The administration of Withaferin A, one of the more than 40 bio-active compounds found in Withania somnifera, has been associated with an improvement across a range of neurodegenerative disease models, including some models of familial ALS.
In fact, a previous study showed that treatment of TDP-43A315T mice, a mouse model of familial ALS with TDP-43 pathology (one of the inherited types of ALS), with Withania somnifera root extract resulted in increased clearance of the mutant TDP-43 protein in motor neurons, improved motor and cognitive performance, and reduction in inflammatory markers.
Therefore, researchers set out to investigate the effect of Withania somnifera in SOD1G93A mice, a mouse model of SOD1-associated ALS.
Results indicated that administration of Withania somnifera extracts in SOD1 mutated mice resulted in an increased lifespan, improved motor performance, and an increased number of motor neurons in the spinal cord.
Importantly, Withania somnifera treatment also led to a substantial reduction in levels of misfolded SOD1 proteins while enhancing levels of cellular chaperones in the spinal cord, which are proteins that guide misfolded or unfolded proteins to revert to their normal conformation.
Withania somnifera significantly reduced activation of glial cells (a cell of the central nervous system) and prevented phosphorylation of nuclear factor kappaB (NF-κB). Both events are associated with a reduction in inflammation.
In fact, administration of Withania somnifera was found to improve the overall immune environment.
Also, use of Withania somnifera was associated with an increase in autophagy, which is a mechanism through which cells clear damaging misfolded or aggregated proteins.
“These results suggest that [Withania somnifera] extracts might constitute promising therapeutics for treatment of ALS with involvement of misfolded SOD1,” researchers wrote.