Ashwagandha

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Information on nutritional supplements people with ALS have been taking

Withania somnifera, commonly known as ashwagandha, is an herb used in Ayurveda medicine.

General effects[edit]

  • Potent anxiolytic effects in the context of chronic stress.[1]
  • Significantly reduces the symptoms of stress, including reduction in cortisol.
  • Reduction seen in C-reactive protein
  • Power output improvements in trained persons and in sedentary persons who simply took the supplement as well as untrained people who began strength training.

Effects on ALS[edit]

  • In SOD1 mice, Withaferin A, a compound in ashwagandha alleviates neuroinflammation, decreases levels of misfolded SOD1 in the spinal cord, reduces loss of motor neurons resulting in delayed disease progression and mortality. WA triggered robust induction of heat shock protein 25 (a mouse ortholog of heat shock protein 27), which may explain the reduced level of misfolded SOD1 species in the spinal cord of SOD1(G93A) mice. [2]
  • In TDP-43 (hTDP-43A315T) mice, ashwagandha root extract ameliorated motor performance on rotarod test and cognitive function assessed by the passive avoidance test. Ashwagandha root improved innervation at neuromuscular junctions, attenuated neuroinflammation, and reduced NF-κB activation. Remarkably, treatment reversed the cytoplasmic mislocalization of hTDP-43 in spinal motor neurons and in brain cortical neurons of hTDP-43A315T mice and it reduced hTDP-43 aggregation. [3]
  • In Drosophila melanogaster model for ALS, the flies are selectively overexpressing the wild human copper, zinc-superoxide dismutase (hSOD1-gain-of-function) in Drosophila motoneurons. Interestingly, Ashwagandha treatment significantly increased lifespan of hSDO1 while Mucuna pruriens had not effect. Conversely, both Ashwagandha and Mucuna pruriens significantly rescued climbing impairment, and also latency and amplitude of ePSPs as well as failure responses to high frequency DLM stimulation. Finally, mitochondrial alterations were any more present in Ashwagandha - but not in Mpe-treated hSOD1 mutants. Hence, given the role of inflammation in the development of ALS, the high translational impact of the model, the known anti-inflammatory properties of these extracts, and the viability of their clinical use, these results suggest that the application of Ashwagandha and Mucuna pruriens might represent a valuable pharmacological strategy to counteract the progression of ALS and related symptoms.[4]

Discussion threads on the ALSTDI forum[edit]

References[edit]

  1. Andrade et al.: A double-blind, placebo-controlled evaluation of the anxiolytic efficacy ff an ethanolic extract of withania somnifera. Indian J Psychiatry 2000;42:295-301. PMID: 21407960. A double-blind, placebo-controlled study was conducted to evaluate the efficacy an ethanolic extract of Aswagandha (Withania somnifera), in patients with ICD-10 anxiety disorders. The sample comprised 39 subjects, of whom 20 received the drug and 19 received placebo. The two groups were sociodemographically and clinically similar at baseline. At 2 and 6 weeks follow-up, data from approximately 85% of patients in each group were available for analysis. Statistical trends favouring the drug were observed at both time points. At 6 weeks, significantly more patients met a priori response criteria in the drug group (88.2%) as compared with the placebo group (50%). The drug was well-tolerated and did not occasion more adverse effects than did placebo. It is concluded that this ethanolic extract of Withania somnifera has useful anxiolytic potential and merits further investigation.
  2. Patel et al.: Early-stage treatment with Withaferin A reduces levels of misfolded superoxide dismutase 1 and extends lifespan in a mouse model of amyotrophic lateral sclerosis. Neurotherapeutics 2015;12:217-33. PMID: 25404049. DOI. Approximately 20% of cases of familial amyotrophic lateral sclerosis (ALS) are caused by mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Recent studies have shown that Withaferin A (WA), an inhibitor of nuclear factor-kappa B activity, was efficient in reducing disease phenotype in a TAR DNA binding protein 43 transgenic mouse model of ALS. These findings led us to test WA in mice from 2 transgenic lines expressing different ALS-linked SOD1 mutations, SOD1(G93A) and SOD1(G37R). Intraperitoneal administration of WA at a dosage of 4 mg/kg of body weight was initiated from postnatal day 40 until end stage in SOD1(G93A) mice, and from 9 months until end stage in SOD1(G37R) mice. The beneficial effects of WA in the SOD1(G93A) mice model were accompanied by an alleviation of neuroinflammation, a decrease in levels of misfolded SOD1 species in the spinal cord, and a reduction in loss of motor neurons resulting in delayed disease progression and mortality. Interestingly, WA treatment triggered robust induction of heat shock protein 25 (a mouse ortholog of heat shock protein 27), which may explain the reduced level of misfolded SOD1 species in the spinal cord of SOD1(G93A) mice and the decrease of neuronal injury responses, as revealed by real-time imaging of biophotonic SOD1(G93A) mice expressing a luciferase transgene under the control of the growth-associated protein 43 promoter. These results suggest that WA may represent a potential lead compound for drug development aiming to treat ALS.
  3. Dutta et al.: Withania somnifera Reverses Transactive Response DNA Binding Protein 43 Proteinopathy in a Mouse Model of Amyotrophic Lateral Sclerosis/Frontotemporal Lobar Degeneration. Neurotherapeutics 2016;. PMID: 27928708. DOI. Abnormal cytoplasmic mislocalization of transactive response DNA binding protein 43 (TARDBP or TDP-43) in degenerating neurons is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Our previous work suggested that nuclear factor kappa B (NF-κB) may constitute a therapeutic target for TDP-43-mediated disease. Here, we investigated the effects of root extract of Withania somnifera (Ashwagandha), an herbal medicine with anti-inflammatory properties, in transgenic mice expressing a genomic fragment encoding human TDP-43(A315T) mutant. Ashwagandha extract was administered orally to hTDP-43(A315T) mice for a period of 8 weeks starting at 64 and 48 weeks of age for males and females, respectively. The treatment of hTDP-43(A315T) mice ameliorated their motor performance on rotarod test and cognitive function assessed by the passive avoidance test. Microscopy examination of tissue samples revealed that Ashwagandha treatment of hTDP-43(A315T) mice improved innervation at neuromuscular junctions, attenuated neuroinflammation, and reduced NF-κB activation. Remarkably, Ashwagandha treatment reversed the cytoplasmic mislocalization of hTDP-43 in spinal motor neurons and in brain cortical neurons of hTDP-43(A315T) mice and it reduced hTDP-43 aggregation. In vitro evidence is presented that the neuronal rescue of TDP-43 mislocalization may be due to the indirect effect of factors released from microglial cells exposed to Ashwagandha. These results suggest that Ashwagandha and its constituents might represent promising therapeutics for TDP-43 proteinopathies.
  4. De Rose et al.: Differential effects of phytotherapic preparations in the hSOD1 Drosophila melanogaster model of ALS. Sci Rep 2017;7:41059. PMID: 28102336. DOI. The present study was aimed at characterizing the effects of Withania somnifera (Wse) and Mucuna pruriens (Mpe) on a Drosophila melanogaster model for Amyotrophic Lateral Sclerosis (ALS). In particular, the effects of Wse and Mpe were assessed following feeding the flies selectively overexpressing the wild human copper, zinc-superoxide dismutase (hSOD1-gain-of-function) in Drosophila motoneurons. Although ALS-hSOD1 mutants showed no impairment in life span, with respect to GAL4 controls, the results revealed impairment of climbing behaviour, muscle electrophysiological parameters (latency and amplitude of ePSPs) as well as thoracic ganglia mitochondrial functions. Interestingly, Wse treatment significantly increased lifespan of hSDO1 while Mpe had not effect. Conversely, both Wse and Mpe significantly rescued climbing impairment, and also latency and amplitude of ePSPs as well as failure responses to high frequency DLM stimulation. Finally, mitochondrial alterations were any more present in Wse- but not in Mpe-treated hSOD1 mutants. Hence, given the role of inflammation in the development of ALS, the high translational impact of the model, the known anti-inflammatory properties of these extracts, and the viability of their clinical use, these results suggest that the application of Wse and Mpe might represent a valuable pharmacological strategy to counteract the progression of ALS and related symptoms.