Phyllodulcin could be a promising Alzheimer’s disease treatment

Hydrangeas' natural sweetener inhibited amyloid β aggregation in an animal model study.


Alzheimer’s disease is a prevalent neurodegenerative disease causing memory loss and cognitive impairment. Its main symptoms are caused by senile plaques of amyloid β aggregates and neurofibrillary tangles, abnormal hyperphosphorylated tau protein aggregates. The amyloid hypothesis suggests that Aβ aggregation contributes to synaptic function deterioration, neuroinflammation, and neuronal apoptosis.

Phyllodulcin, a naturally occurring sweetener in hydrangea, is being studied in a novel rat model study to determine how it affects A buildup. The findings point to phyllodulcin’sphyllodulcin’s potent inhibition of A buildup and decomposition of pre-aggregated A, pointing to its usefulness in treating AD.

The major cause of Alzheimer’s disease (AD) is thought to be brain lesions induced by the aggregation of amyloid (A) and neurofibrillary tangles. As a result, treatment drugs that inhibit A aggregation may delay AD’s development and progression.

Although various medicines targeting A have been developed, clinical trial investigations have shown they are ineffective. The usage of authorized antibody medicines is coupled with high treatment costs and unknown efficacy. As a result, creating a simple and effective medication targeting A for treating Alzheimer’s disease is required.

Phyllodulcin, a natural sweetener found in Hydrangea macrophylla var. thunbergia, has been proven to efficiently cross the blood-brain barrier and be distributed uniformly throughout the brain. However, the significance of phyllodulcin in managing Alzheimer’s disease has not been explored.

Assistant Professor Se Jin Jeon of Sahmyook University‘s Department of Integrative Biotechnology and a group of Korean researchers investigated the effect of phyllodulcin on aggregation and numerous clinical characteristics in an animal model of AD.

The researchers hypothesized that phyllodulcin could enter the brain and block A aggregation, improving numerous brain lesions in Alzheimer’s disease. Both in vivo (cells) and in vitro (animal model) tests revealed that phyllodulcin could efficiently suppress A aggregation and dissolve pre-aggregated A clumps. A toxicity assay also demonstrated that phyllodulcin protects against A-induced neurotoxicity attributable to fewer A aggregates.

Elaborating on these findings, Assistant Professor Jeon said, “Our study is the first to report that phyllodulcin can modify the underlying pathogenesis of Alzheimer’s disease, suggesting the possibility of preventing dementia or delaying the progression of the disease. It will take more than 20 years to develop a treatment, but at this stage, the results of this study can be used to provide a guide map that can help prevent or improve dementia symptoms.”

The new study is the first to show that phyllodulcin may modify the underlying cause of Alzheimer’s disease, raising the prospect of avoiding dementia or slowing its progression. The findings of this study could serve as a road map for preventing or improving dementia symptoms.

The result shows that phyllodulcin is a promising option for creating drugs for treating Alzheimer’s disease.

Journal Reference:

  1. Eunbi Cho, Se Jin Jeon, et al. Phyllodulcin improves hippocampal long-term potentiation in 5XFAD mice. Biomedicine & Pharmacotherapy. DOI: 10.1016/j.biopha.2023.114511
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