Ashwagandha For Alzheimer's and Parkinson's Disease
The brain regulates the function of many organs. When it is healthy, it works quickly and efficiently. However, when problems occur, the effects can be devastating.
Neurodegenerative diseases cause degeneration of nerve cells which lead to slow death of neurons. The most common neurodegenerative diseases are Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease.1
Alzheimer’s disease is known to cause memory loss and behavior issues due to damage of brain cells – it is the most common cause of dementia. It is a progressive disorder which worsens over time – in later stages, patients can lose their ability to respond to the environment e.g. carrying on a conversation. While Alzheimer’s is usually associated with aging (typically above 65 years of age), early-onset Alzheimer’s has been known to happen to those in their 40s and 50s too.
Risk factors are usually associated with genetics and family history, but head trauma, brain and heart disorders have been linked to Alzheimer’s as well.
Parkinson’s disease (PD) is a slowly progressive degenerative disorder of the central nervous system that affects movement, muscle control, and balance. Even today, it remains a progressive and incurable condition.
Normally, brain cells, concentrated in a part of the brain called substantia nigra, produce a neurotransmitter dopamine that relays messages to other parts of the brain to control body movements. In a person suffering from PD, the cells stop producing dopamine. With less and less dopamine, a person has less and less ability to regulate their movements, body and emotions. In fact, current research suggests that non-motor symptoms, such as a loss of sense of smell, hyposmia, sleep disorders and constipation may precede the motor features of the disease by several years.2
Parkinsons’ disease (PD) has been linked with genetic and environmental factors, mainly industrial chemicals (specific insecticides, fungicides, pesticides and neurotoxins like MTBT).
Neurodegeneration: Underlying Causes
Neurodegenerative diseases are characterized by the formation of protein aggregates in the brain, typically due to misfolding of specific proteins. Protein aggregates cause damage and death of brain cells (neurons) and loss of synapses.
Protein aggregates containing beta-amyloid and hyperphosphorylated tau are characteristic of Alzheimer’s disease.
Amyloid Beta proteins are the main components of plaques found in Alzheimer’s patients. This plaque build up damages the vascular tissues and leads to death of nerve cells.3
Abnormal neuron threads contain Tau protein and ubiquitin which play a major role in the cognitive impairment of this disease. The normal neuron networks in brain help in carrying information through its internal transport systems. However, when these threads twist abnormally and form tangles the transport of nutrients and other essential materials fail. This in turn leads to brain cell damage causing variety of effects on human behavior.4
In PD, the protein alpha-synuclein tends to accumulate and form spherical inclusions called Lewy bodies. There is some evidence connecting the presence of Lewy bodies to the death of dopamine producing neurons.5
Neurodegenerative Mechanisms May Be Interconnected
Worryingly, the mechanisms of formation of alpha-synuclein Lewy bodies, beta-amyloid plaques and tau tangles seem to be interconnected and likely to promote the aggregation and accumulation of each other – with accelerated progression of disease conditions.6
Dementia is increasingly being recognized in cases of Parkinson’s disease (PD); such cases are termed PD dementia (PDD). The spread of fibrillar α-synuclein (α-syn) pathology from the brainstem to limbic and neocortical structures seems to be the strongest indicator of emerging dementia in PD.
Up to 50% of patients with PDD also develop sufficient numbers of amyloid-β plaques and tau-containing neurofibrillary tangles for a secondary diagnosis of Alzheimer’s disease.7
Chronic inflammation could also be a cause of (or a contributing factor to) neurodegeneration. Neurons are especially vulnerable to free radical attack and impaired defenses or exposure to excess free radicals can lead to neuronal death. Free radicals contribute to neuronal loss in cerebral ischemia and hemorrhage and may be involved in the degeneration of neurons in epilepsy, schizophrenia, tardive dyskinesia, normal aging, Parkinson’s Disease and Alzheimer’s Disease.8
The evidence for a chronic inflammatory reaction in the brain is particularly strong in Alzheimer’s disease (AD), where it has been extensively studied, but there is also evidence suggesting that a local immune reaction occurs in affected regions of the brain in Parkinson’s disease (PD):
- Elevated levels of complement proteins, including all elements of the membrane attack complex, in the substantia nigra
- Profusion of reactive microglia is seen in the substantia nigra and striatum
- Increased level of inflammatory cytokines in the substantia nigra
- Increased lipid peroxidation
All of the above contribute to death of neurons.
It seems possible that treatment with anti-inflammatory agents might slow the progress of dopaminergic cell death in PD. Anti-inflammatory treatment of PD cases might also serve to inhibit the onset of dementia, a condition to which those with parkinsonism seem to be more prone than the general population.9
How Does Ashwagandha Work Against Neurodegeneration?
Reduces Oxidative Stress and Inflammation
Ashwagandha has powerful anti-inflammatory, anti-oxidant, and free radical scavenging properties. These properties explain why Ashwagandha has been considered to be a wonder herb in Ayurveda to improve vitality and strength.
Potent anti-inflammatory activity of Ashwagandha has been attributed to biologically active steroids, of which Withaferin A is a major component. It is as effective as hydrocortisone sodium succinate, dose for dose.10
Withaferin A has been found to increase the activity of the most important enzymes of the cell anti-oxidant defense system – superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) – in rat brain frontal cortex and striatum. Antioxidant effect of active glycowithanolides of Ashwagandha may explain, at least in part, the reported anti-inflammatory, immunomodulatory, anti-stress, antiaging and cognition-facilitating effects produced by them in experimental animals, and in clinical situations.11
Mouse studies have shown that treatment with Ashwagandha extract significantly reduces oxidative damage by improving antioxidant enzyme levels, and significantly improves physiological indicators of PD such as grooming, stride length, movement, rearing, narrow beam walk and foot slippery errors.12
Clears Protein Clumps In The Brain
Ashwagandha has been found to clear beta-amyloid peptides and reverse the behavioral deficits and pathology seen in Alzheimer’s disease models. The mechanism is indirect – beta amyloid clearance is induced by enhancing LDL receptor-related protein in the liver.13 14
Increases Dopamine Levels
Ashwagandha extract improves dopamine levels and reverses all parameters associated with oxidative stress – clearly demonstrating its overall effectiveness against Parkinson’s disease.15 16
Reconstructs Neuronal Networks
Neurodegenerative diseases are typically associated with death of neurons and synaptic loss. Ashwagandha is an important candidate for the therapeutic treatment of neurodegenerative diseases, as it’s constituents are able to reconstruct neuronal networks and synapses, regenerate axons and dendrites and improve memory deficits.17
Neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease are a result of damage and death of cells in the brain, typically caused by oxidative stress and inflammation. Ashwagandha, with its potent antioxidant, anti-inflammatory, and neuroprotective properties, not only helps prevent such damage, but also repair, recover and heal, if damage has already occurred. This makes it a wonderful option to include, either on its own, or as a complementary medicine, in the treatment of often difficult-to-treat diseases of the brain such as Parkinson’s and Alzheimer’s.
References [ + ]
|1.||↑||Protein aggregation and neurodegenerative disease. Nature. 2004.|
|2.||↑||What is Parkinson’s?. National Parkinson Foundation|
|3.||↑||Hardy, John A, Higgins, Gerald A. Alzheimer’s Disease: The Amyloid Cascade Hypothesis. 1992.|
|4.||↑||Tau, tangles, and Alzheimer’s disease. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease. 2005.|
|5.||↑||Luk, Kelvin C., Victoria Kehm, Jenna Carroll, Bin Zhang, Patrick O’Brien, John Q. Trojanowski, and Virginia M-Y. Lee. “Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice.” Science 338, no. 6109 (2012): 949-953.|
|6.||↑||Marsh, Samuel E., and Mathew Blurton-Jones. “Examining the mechanisms that link beta-amyloid and alpha-synuclein pathologies.” Alzheimers Res Ther 4, no. 2 (2012): 11.|
|7.||↑||Irwin, David J., Virginia M-Y. Lee, and John Q. Trojanowski. “Parkinson’s disease dementia: convergence of [alpha]-synuclein, tau and amyloid-[beta] pathologies.” Nature Reviews Neuroscience 14, no. 9 (2013): 626-636.|
|8.||↑||Jesberger, James A., and J. Steven Richardson. “Oxygen free radicals and brain dysfunction.” International journal of neuroscience (2009).|
|9.||↑||McGeer, Edith, Koji Yasojima, and Patrick L. McGeer. “Inflammation and the pathogenesis of Parkinson’s disease.” British Columbia Medical Journal 43, no. 3 (2001): 138-141.|
|10.||↑||Khare CP. Indian Medicinal Plants–An Illustrated Dictionary. First Indian Reprint, Springer (India) Pvt. Ltd., New Delhi (2007) 717-718.|
|11.||↑||Bhattacharya, S. K., Kalkunte S. Satyan, and Shibnath Ghosal. “Antioxidant activity of glycowithanolides from Withania somnifera.” Indian Journal of Experimental Biology 35 (1997): 236-239.|
|12.||↑||RajaSankar S, Manivasagam T, Surendran S. Ashwagandha leaf extract: A potential agent in treating oxidative damage and physiological abnormalities seen in a mouse model of Parkinson’s disease. Neuroscience Letters. 2009.|
|13.||↑||Sehgal, Neha, Alok Gupta, Rupanagudi Khader Valli, Shanker Datt Joshi, Jessica T. Mills, Edith Hamel, Pankaj Khanna, Subhash Chand Jain, Suman S. Thakur, and Vijayalakshmi Ravindranath. “Withania somnifera reverses Alzheimer’s disease pathology by enhancing low-density lipoprotein receptor-related protein in liver.” Proceedings of the National Academy of Sciences 109, no. 9 (2012): 3510-3515.|
|14.||↑||[Prakash J, Yadav SK, Chouhan S, Singh SP. Neuroprotective role of Withania somnifera root extract in maneb-paraquat induced mouse model of parkinsonism. Neurochem Res. 2013 May;38(5):972-80. doi: 10.1007/s11064-013-1005-4.]|
|15.||↑||RajaSankar S, Manivasagam T, Sankar V, Prakash S, Muthusamy R, Krishnamurti A, Surendran S. Withania somnifera root extract improves catecholamines and physiological abnormalities seen in a Parkinson’s disease model mouse. J Ethnopharmacol. 2009 Sep 25;125(3):369-73. doi: 10.1016/j.jep.2009.08.003.|
|16.||↑||Ahmad M, Saleem S, Ahmad AS, Ansari MA, Yousuf S, Hoda MN, Islam F. Neuroprotective effects of Withania somnifera on 6-hydroxydopamine induced Parkinsonism in rats. Hum Exp Toxicol. 2005 Mar;24(3):137-47.|
|17.||↑||Kuboyama, Tomoharu, Chihiro Tohda, and Katsuko Komatsu. “Neuritic regeneration and synaptic reconstruction induced by withanolide A.” British journal of pharmacology 144, no. 7 (2005): 961-971.|