Passion Fruit Molecule: Potential Alzheimer's Drug

Four years ago, a research group at the University of Oslo made what would turn out to be a major discovery. They found that an extract from passion fruit had the potential to slow the development of Alzheimer's‑like brain damage.

What is it about this small fruit that might promote healthy ageing and slow the progression of dementia?

So far, this has not been tested in humans. However, the researchers have made an exciting new discovery that could significantly accelerate this line of research.

"After four years of hard work, we have managed to uncover what the passion fruit's secret is," says Professor Evandro Fei Fang‑Stavem at the University of Oslo and Akershus University Hospital.

Inside passion fruit there is a molecule called alpha‑amyrin, α‑amyrin for short. It appears to have some very special properties.

"Our study shows that alpha‑amyrin has the ability to protect some absolutely central processes in the brain. And we believe that we may be able to use this molecule in a medicine for Alzheimer's disease if it also proves effective in future clinical trials against this difficult-to-treat disease," says Fang‑Stavem.

The study has been published in the journal Advanced Science.

Alpha-amyrin acts as a "brain guardian"

Alzheimer's disease is a disorder of the brain that develops slowly over several years. It is the most common cause of dementia. People who develop the disease experience memory problems, struggle with language and may have difficulty finding their way. They also often undergo changes in personality.

The disease is characterised by a build‑up of waste products in the brain. This "rubbish" consists of proteins, which damage nerve cells and eventually cause them to die.

"Alpha‑amyrin acts like a kind of "brain guardian", helping to prevent this rubbish from building up," explains postdoctoral fellow Shu‑qin Cao, a 1st author of this study from the University of Oslo.

Brain cells are vulnerable to changes that occur as we age

Our brain needs a great deal of energy to function properly. When waste products accumulate in the brain, the brain's energy factories are no longer able to produce enough energy.

These energy factories are called mitochondria, which are sub-cellular organelles found in almost all our cells.

As we grow older, the cells in the brain are not always able to clear away this waste.

"Our brain cells are vulnerable to the changes that take place in the body as we age. They depend on the mitochondria producing enough energy, but this system does not work as well when waste products build up," explains Cao, and continues:

"So, the fact that alpha‑amyrin found in passion fruit actually protects the mitochondria is a major finding."

The food you eat today may affect your brain in the future

Passion fruit is not the only type of fruit that contains alpha‑amyrin. It is also found in a number of other colourful fruits, berries and vegetables, such as tomatoes and cranberries.

In the study, the researchers also looked at epidemiological data from a period of 10 years on nutrition and dementia.

"Our 10-year epidemiological data strongly indicate that a high consumption of colourful and nutritional fruits, such as passion fruit, correlates with low dementia risk," says Fang-Stavem.

"We know from previous research that a high intake of colourful fruit and vegetables is good for the brain. Now we see that these benefits are likely to come from natural ingredients found in this kind of fruit and vegetables, especially in passion fruit. These ingredients protect the mitochondria and help preserve memory," says Cao.

She points out that more research is needed.

"Even so, there is growing evidence that what we eat today can influence our brain health many years into the future."

Shu and Evandro in the laboratory holding passion fruit
Postdoctoral fellow Shu-qin Cao and Professor Evandro Fei Fang-Stavem study the molecule alpha-amyrin found in passion fruit and other colourful fruits, berries and vegetables. Image: Birgit Solhaug: UiO

Mice with Alzheimer's-like brain pathology had better memory when given supplements

In the study, the researchers examined what happened when mice with Alzheimer's‑like brain pathology were given supplements of alpha‑amyrin.

They observed that fewer waste products accumulated.

"Alpha‑amyrin supported the brain's own control system and helped the cells to remove the rubbish, so that the mitochondria could function normally," says Cao.

The mice also performed better in memory tests.

The researchers discovered that alpha‑amyrin promotes activation of a protein called ULK1. They believe this is one of the underlying mechanisms that explains how the molecule protects the brain.

"The protein ULK1 has an important role in mitochondrial quality control by initiating autophagy and facilitating the removal of damaged mitochondria," Cao explains.

Can alpha-amyrin function as an active ingredient in a future medicine?

For a molecule to function as an active substance in a medicine, it needs to have certain specific properties. It must be able to reach the part of the body it is intended to treat. It must also remain in the body long enough to have an effect.

In the study, the researchers tested this in young, healthy mice. These animals did not need any treatment, but the researchers wanted to see how alpha-amyrin behaved.

"We saw that the molecule is able to move from the bloodstream into the brain in these mice, which indicates that it is possible to get the molecule to reach the brain," she says.

A possible future medicine for Alzheimer's?

Fang-Stavem, Cao and colleagues believe they are on the trail of a possible future medicine for Alzheimer's disease.

"We would like bring our investigations of alpha-amyrin further, such as to perform clinical trials on its bioavailability, safety, and efficacy against dementia, when funding and resources are available", Cao explains.

The researchers are moving forward towards the direction of commercialisation.

Through the UiO's Technology Transfer Office (TTO) Inven2 AS, UiO has licensed commercial development of alpha amyrin, within the field of food supplements to improve general health, to a Hong Kong-based company, the HK Longevity Science Laboratory (HKLSL).

"HKLSL aims to develop a passion fruit extract containing alpha-amyrin as a food supplement," says Fang-Stavem.

The research group
An international research team. On the photo: Beatriz Escobar Doncel, Haijun He, He-Ling Wang, Ingrid Flatåker, Jianying Zhang, Johannes Frank, Shuqin Cao, Sofie Mielenz, Tomas Schmauck-Medina, Jun-ping Pan og Evandro Fei Fang-Stavem. Image: Birgit Solhaug, UiO
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