Herbs And Phytochemicals: Urolithin A From Pomegranates Improves Treatment Of Alzheimer's Disease

Herbs And Phytochemicals: Alzheimer's disease, a devastating neurodegenerative condition, is characterized by symptoms like forgetfulness, difficulty in finding words, and confusion about time and place. Despite significant research, finding an effective treatment has been challenging. However, a recent Herbs And Phytochemicals study by researchers at the University of Copenhagen Tongji University, Shanghai-China and the National Institute on Aging, Baltimore, Maryland-USA has brought a glimmer of hope. They discovered that urolithin A, a substance naturally occurring in pomegranates, strawberries, and walnuts, can potentially improve memory and aid in the treatment of Alzheimer's disease.


Urolithin A From Pomegranates Improves Treatment Of Alzheimer's Disease

A Promising Discovery
The study, conducted on mouse models of Alzheimer's disease (AD), demonstrated that urolithin A can alleviate memory problems and other symptoms of dementia. Vilhelm Bohr, an Affiliate Professor at the University of Copenhagen's Department of Cellular and Molecular Medicine, and former Department Chair at the US National Institute on Aging, emphasized the significance of these findings. "Our study shows that urolithin A, a naturally occurring substance in pomegranates, can alleviate memory problems and other consequences of dementia," Bohr stated.
 
Mechanisms of Action
The researchers previously identified that nicotinamide riboside (NAD supplement), a molecule critical in neurodegenerative diseases like Alzheimer's and Parkinson's, plays a key role in removing damaged mitochondria from the brain. This process, known as mitophagy, is often impaired in patients with neurodegenerative diseases, leading to mitochondrial dysfunction. "If you are able to stimulate the mitophagy process, removing weak mitochondria, you will see some very positive results," Bohr explained.
 
The new study revealed that urolithin A removes weak mitochondria from the brain as effectively as NAD supplements. This finding is particularly significant as it suggests a potential new avenue for treating Alzheimer's disease by targeting mitochondrial health.
 
The Potential for Human Application
While the study was conducted on mice, the researchers are optimistic about the potential for human applications. "Even though the study was conducted on mouse models, the prospects are positive. So far, research has shown promising results for the substance in muscles, and clinical trials on humans are being planned," Bohr said.
 
However, the researchers still need to determine the precise dosage of urolithin A required to improve memory and alleviate Alzheimer's symptoms. "We still cannot say anything conclusive about the dosage. But I imagine that it is more than a pomegranate a day. The substance is already available in pill form, and we are currently trying to find the right dosage," Bohr added .
 
A Natural Solution with Minimal Side Effects
One of the significant advantages of using a natural substance like urolithin A is the reduced risk of side effects. Bohr noted that several studies have shown no serious side effects from NAD supplementation. While the knowledge of urolithin A is more limited, preliminary results are promising. "If we are going to eat something in the future to reduce the risk of Alzheimer's, we have to make sure there are no significant side effects," Bohr emphasized.
 
Urolithin A: Mechanisms and Effects
The study highlighted the mechanisms by which urolithin A improves Alzheimer's disease symptoms. The researchers found that long-term urolithin A treatment significantly improved learning, memory, and olfactory function in various AD transgenic mice. Additionally, urolithin A reduced amyloid beta (Aβ) and tau pathologies, enhanced long-term potentiation, and improved cellular lysosomal function by normalizing lysosomal cathepsins, particularly cathepsin Z.
 
Insights from Previous Research
Previous research has shown that mitophagy, the process of clearing damaged mitochondria, is crucial for maintaining normal physiological function and neuron health. In Alzheimer's patients, mitophagy is often compromised, leading to the accumulation of damaged mitochondria. Natural mitophagy inducers like urolithin A, nicotinamide riboside (NR), kaempferol, and rhapontigenin have shown promise in reducing Alzheimer's symptoms.

Urolithin A is a gut microbial metabolite of ellagic acid, found in pomegranates, berries, and nuts. It was discovered 40 years ago but has only recently been explored for its impact on aging and diseases. Urolithin A has been shown to prolong the lifespan of Caenorhabditis elegans, improve muscle function, and reduce inflammation.
 
Long-term Effects of Urolithin A
The recent study extended previous research by treating multiple AD mouse models with urolithin A for five months. The findings showed significant improvements in cognitive function, olfactory ability, synaptic function, and reductions in neuroinflammation and DNA damage. The study also highlighted the role of cathepsin Z in the therapeutic effects of urolithin A on Alzheimer's disease.
 
The Role of Cathepsin Z
One of the most significant findings was that cathepsin Z (Ctsz) plays a critical role in urolithin A-induced therapeutic effects. Ctsz, a lysosomal enzyme, was highly expressed in multiple AD transgenic mouse models, and its expression normalized after urolithin A treatment. The study suggests that Ctsz is involved in regulating lysosomal function and neuroinflammation, making it a potential target for Alzheimer's treatment.
 
Future Implications
The study's results provide a strong foundation for future translational research. The detailed comparison of short-term and long-term urolithin A treatment highlights its potential as a therapeutic agent for Alzheimer's disease. Urolithin A's ability to improve mitochondrial function, reduce neuroinflammation, and normalize lysosomal cathepsins presents a promising approach to combating Alzheimer's disease.
 
Conclusion
The discovery of urolithin A's benefits in treating Alzheimer's disease marks a significant advancement in the quest for effective treatments. While more research is needed to determine the precise dosage and long-term effects in humans, the findings offer hope for a future where natural substances like urolithin A can play a crucial role in mitigating the impact of Alzheimer's disease. As clinical trials progress, the potential for urolithin A to improve the lives of those affected by Alzheimer's becomes increasingly promising.
 
The study findings were published in the peer reviewed journal: Alzheimer’s And Dementia.
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13847
 
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