Can Sesame Seed Shells Prevent Parkinson's Disease? A Look at Recent Research

Parkinson’s disease is a debilitating and often fatal disease that causes tremors and impairs proper movement. The disease is a result of neurodegenerative changes that cause a part of the brain known as the substantia nigra to shrink and function deficiently. Existing therapies are intended to manage symptoms, but there is no current treatment for restoring the neurodegenerative changes caused by the disease.

Now, a group of researchers from the University of Osaka have recently published a study in the journal Heliyon that proposes the use of a byproduct of sesame oil production called sesaminol for the prevention of the disease (1). Professor Akiko Kojima-Yuasa led the team of researchers in the development of a preventive agent sourced from the shells of sesame seeds that under normal circumstances is discarded as industrial waste. These results reveal a new candidate for the preventive treatment of Parkinson’s disease.

Antioxidants Are Key to Preserving Healthy Neurons

Previous research shows that it is possible to prevent damage to neurons through the use of antioxidants (2). In Parkinson’s disease, neurons from the substantia nigra — a critical brain region that affects many systems, including movement control and cognitive executive functions — are damaged because of an excessive amount of oxidative stress caused by the production of harmful compounds called reactive oxygen species (ROS). Under normal circumstances, ROS are kept under control through naturally occurring antioxidants (3).

One ROS precursor known as oxidopamine (6-OHDA) has effects on neurons in the substantia nigra. Oxidopamine competes with dopamine, a critical brain signaling molecule that plays a major role in Parkinson’s disease, to bind to receptors on substantia nigra neurons. This competition makes communication between cells difficult, propagating disease effects. Also, oxidopamine becomes a source of ROS, which damage our genetic code and proteins essential for cellular structures like mitochondria (4). When this damage occurs, these dysfunctional cells die as part of a programmed cellular death process known as apoptosis.

Sesaminol Fights the Damage Caused by Oxidative Stress

Some of the effects of Parkinson’s disease are a result of the damage done to neurons by the imbalance between ROS and antioxidants. The imbalance created by this oxidative stress puts pressure on the brain’s coping mechanisms. Professor Kojima-Yuasa’s team examined a protein involved in one of these coping strategies, a protein known as Nrf2 that is usually present within the cellular nucleus. Here, Nrf2 can trigger a response to neutralize the damaging effects of ROS on the cell’s DNA, protecting against oxidative stress by activating genes encoding antioxidant enzymes. The researchers tested the effect of the antioxidant byproduct of sesame oil, sesaminol, on cells in a dish similar to the ones present in the substantia nigra, as well as in an animal model of Parkinson’s disease.

For the first series of tests, the cultured brain cells were exposed to the ROS precursor oxidopamine and compared to untreated control cells. The researchers found that the viability and function of the cells that had been exposed to the oxidopamine diminished consistently with increasing amounts of oxidopamine. Kojima-Yuasa’s team then saw how sesaminol treatment affected the compromised cells. ROS increased significantly after the exposure to oxidopamine, but the addition of sesaminol was able to restore viability and function of these exposed cells to levels similar to those seen in the control group.

Upon further inspection, the nuclear localization of Nrf2 became more prominent in cells that received sesaminol, which suggests an increase in Nrf2 activity. Once the cells were exposed to 6-OHDA, the damaging effects on DNA began by unraveling the packaging of the DNA in the nucleus, a critical step that leads to apoptosis. The addition of sesaminol enhanced Nrf2 levels, and after a few hours, the DNA organization had been restored, preventing the cell from dying.

Sesaminol Prevents the Loss of Dopamine

Kojima-Yuasa and colleagues went one step further, going from studying cells in a dish to live animals, since Parkinson’s disease has effects that can be seen throughout the body. For example, Parkinson’s disease patients, who have impaired movement and tremors, also have gastrointestinal issues like constipation because the gut’s movement is affected (5).

So, the researchers monitored the movements and gastrointestinal activity of  Parkinson’s diseased lab mice and tested whether sesaminol could mitigate these processes. They monitored the dopamine levels as the disease progressed, and, as expected, levels of the neurotransmitter dropped considerably and, with it, movement and gastrointestinal activity. But when these mice were supplemented with sesaminol for a few weeks, dopamine was restored to its previous levels. What Kojima-Yuasa and colleagues saw as a result of this was that the mice’s movements improved significantly and their gastrointestinal activity went back to normal.

This pioneering study shows that sesaminol could provide the first therapeutic agent to actually reverse the effects of Parkinson’s disease. The next step will be clinical trials to evaluate the effectiveness of this naturally-derived substance that is typically thought of as waste in humans. 

References:

1.     Kaji H, Matsui-Yuasa I, Matsumoto K, Omura A, Kiyomoto K, Kojima-Yuasa A. Heliyon. 2020;6(11):e05342. Published 2020 Nov 2. 
2.     Lim JL, Wilhelmus MM, de Vries HE, Drukarch B, Hoozemans JJ, van Horssen J. Arch Toxicol. 2014;88(10):1773-1786. 
3.     Patel M. Trends Pharmacol Sci. 2016;37(9):768-778. 
4.     Bose A, Beal MF. J Neurochem. 2016;139 Suppl 1:216-231. 
5.     Fasano A, Visanji NP, Liu LW, Lang AE, Pfeiffer RF. Lancet Neurol. 2015;14(6):625-639.