Active Ingredient in Aged Garlic Extract Studied on Mice for Effect on Alzheimer’s Disease

Alzheimer’s disease is the most common form of dementia in older people and the 7th leading cause of death in the United States. Years before symptoms of Alzheimer’s disease appear, peptides called amyloid-beta start depositing in the brain. This results in destabilization of microtubules that are responsible for transportation of cellular material, as well as swelling in the brain. The swelling causes damage to neurons and neuronal networks, resulting in dementia in older people. The available treatments do not completely cure Alzheimer’s disease, and new drug targets are being investigated. Garlic extract and S-allyl-L-cysteine (SAC), a component present in the extract, were tested for their effect on neuronal degeneration related to Alzheimer’s disease on mice.

The proportion of elderly population with Alzheimer’s disease is increasing worldwide. Three main features of this disease are: deposition of amyloid-beta peptides causing brain inflammation that damages neurons; chemical changes in tau protein affecting cellular transport via microtubules; and loss of neurons releasing acetylcholine that controls the functions of heart and muscles. The available drugs that target single steps in the progression of the disease can provide some symptomatic relief, but these drugs cannot control or cure the disease. “We hypothesize that an agent effective in modulating multiple pathological pathways could be an appropriate therapeutic agent in preventing and restricting Alzheimer’s disease progression.” Natural substances such as garlic and turmeric are tested because of their low costs, easy availability and fewer possible side effects. Garlic affects different aspects of the progression of the disease, showing the potential to be a possible cure for Alzheimer’s disease.

* Garlic has sulfur-containing compounds that can be unfavorable. When garlic is soaked in ethanol-water mixture for 20 months, unfavorable compounds are destroyed and useful ones become solubilized. The result is aged garlic extract (AGE) and it contains S-allyl-L-cysteine or SAC.
* In vitro and in vivo studies were performed on mouse and rat models of Alzheimer’s disease using these extracts.
* The changed chemical status (phosphorylation) of tau protein was tested in mice with Alzheimer’s disease treated with or without AGE and SAC.
* The chemicals that increase upon inflammation were recorded.

* In vitro studies with SAC showed that it can dissolve amyloid-beta plaques. In vivo, four-month-long treatment with AGE and SAC decreased the number of plaques in the brains of mice.
* Mice with Alzheimer’s disease showed tangled neuronal microtubules due to chemical changes in tau protein. The treatment with AGE and SAC showed decreased levels of the changed tau protein.
* Garlic extract treatment showed increase in the levels of glutathione, an enzyme that protects neurons from inflammatory agents.
* The changes in various other factors seen in the disease improved with AGE or SAC treatment.

Shortcomings/Next steps
Authors recommend more research and have confirmed that the “current FDA-approved drugs for the treatment of Alzheimer’s disease fail to completely cure the disease.” Most of the new drugs that have been tried in clinical trials have failed to demonstrate definite curative effects in these trials. The authors also propose a combined formulation of curcumin with AGE or SAC, which can produce synergistic properties to alleviate the pathology of Alzheimer’s disease, and its associated symptoms, and these types of combinations would also require further research in preclinical and clinical settings.

The numbers and cost of treatment of patients with Alzheimer’s disease is increasing, emphasizing the need for a cheaper and more successful new treatment. The authors suggest that the failure to find a cure is because of the multi-faceted nature of this disease. A drug will have to address all these aspects of the pathology to prove to be successful as a treatment for Alzheimer’s disease. The ingredients present in AGE seem to reduce the chemical changes in proteins affecting transport in brain cells, and also affect many aspects of interconnected chemical pathways to reduce swelling in the brain. While more research is needed, remedies such as garlic and curcumin (turmeric) are potentially beneficial in restricting the symptoms of Alzheimer’s disease.

For More Information:
The “Aged Garlic Extract” and One of its Active Ingredients S-Allyl-L-Cysteine as Potential Preventive and Therapeutic Agents for Alzheimer’s Disease
Publication Journal: Current Medicinal Chemistry, 2011
By B. Ray; N.B. Chauhan; Indiana University School of Medicine, Indianapolis and University of Illinois, Chicago

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