Liquorice – can it be used to treat Parkinson’s disease? · PDF fileLiquorice...

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Liquorice – can it be used to treat Parkinson’s disease? Katrina Wallen, Institute of Medical Sciences, University of Aberdeen Can liquorice extract protect against Parkinson’s disease? Katrina Wallen, supervised by Dr Peter Teismann, Institute of Medical Sciences, University of Aberdeen. Introduction Parkinson’s disease is a common neurodegenerative disorder affecting ~10,000 newly diagnosed patients every year in the UK. Major symptoms are tremor, muscle stiffness, paucity of voluntary movements and postural instability. The disease affects not only the patient, but also relatives and people involved in their care. What is the problem? The symptoms of Parkinson’s disease are due to the loss of nerve cells – dopaminergic neurons – in a specific region of the brain. These nerve cells play an important part in the brain involving the production and release of dopamine. Dopamine release from these cells is critical for normal movement. In the majority of cases, Parkinson’s disease arises spontaneously and why the neurons die is still not known. What we found and what it means Treatment with glycyrrhizin had no effect on cell numbers in healthy animals, thus confirming that, by itself, glycyrrhizin is not toxic. MPTP led to a significant reduction of dopaminergic neurons remaining. Although the lower dose of glycyrrhizin was not able to protect against the cell loss, the higher dose did provide protection against MPTP- induced cell death. What we did First, we gave mice MPTP, a chemical neurotoxin which produces the same features as Parkinson’s disease. Acknowledgements With thanks to Rohit Shrivastava and Ross Mounsey, Institute of Medical Sciences, for their help with this project. Symptoms occurring in Parkinson’s disease (from http://www.doctortipster.com/10064-parkinson-disease-symptoms-and-diagnosis.html) Neuropathology of Parkinson’s disease. Schematic representation of the (A) normal and (B) diseased nigrostriatal pathway. In Parkinson’s disease, the pathway degenerates, with a marked loss of the dopaminergic neurons that project to the putamen (dashed line) and a much more modest loss of those that project to the caudate (solid line) (adapted from Dauer & Przedboreski, Neuron (2003) 39:889–909). The most potent treatment for Parkinson’s disease is L-DOPA, a dopamine precursor. By replenishing the brain with dopamine, L-DOPA alleviates almost all Parkinson’s symptoms, but it does lead to side effects that are eventually as debilitating as the disease itself. Therefore a treatment aimed at the main cause of the disease – the degeneration of these neurons – is needed urgently, to enable a later start to the debilitating symptoms and thus an increased quality of life and life expectancy. We want to establish how to protect these brain cells and thus prevent Parkinson’s disease using a component from licorice. Glycyrrhizin, the main component of liquorice, has been shown to interfere with the pathways leading to cell death, so is capable of protecting cells against neurotoxicity. The effect of MPTP (lower panel) on dopaminergic neurons in the substantia nigra and the striatum compared with (upper panel) untreated mouse brain. Then some animals were given glycyrrhizin at different concentrations (16.8mg/kg or 50mg i.p.), with a control group receiving just saline solution. The brains were then deep frozen, sectioned with a cryostat (30µm) and the sections collected and stained for an enzyme called tyrosine-hydroxylase, a specific marker for dopaminergic neurons. These cells were counted using a computer-based counting system. The aim was to clarify whether, if glycyrrhizin did prevent the cells from dying, what concentration would be needed. Dopaminergic neurons are resistant against MPTP after receiving a high dose (50 mg i.p.) but not a low dose (16.8 mg/kg i.p.) of glycyrrhizin *, P <0.05, compared with MPTP-treated controls (Newman–Keuls posthoc test). Glycyrrhizin, the main compound of liquorice, provides protection in our model of Parkinson’s disease. It might, therefore, be able to provide protection in patients suffering from the disease and lead to a slowing of disease progression.

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Page 1: Liquorice – can it be used to treat Parkinson’s disease? · PDF fileLiquorice – can it be used to treat Parkinson’s disease? Katrina Wallen, ... prevent Parkinson’s disease

Liquorice – can it be used to treat Parkinson’s disease? Katrina Wallen, Institute of Medical Sciences, University of Aberdeen

Can liquorice extract protect against Parkinson’s disease? Katrina Wallen, supervised by Dr Peter Teismann, Institute of Medical Sciences, University of Aberdeen.

IntroductionParkinson’s disease is a common neurodegenerative disorder affecting ~10,000 newly diagnosed patients every year in the UK. Major symptoms are tremor, muscle stiffness, paucity of voluntary movements and postural instability. The disease affects not only the patient, but also relatives and people involved in their care.

What is the problem?The symptoms of Parkinson’s disease are due to the loss of nerve cells – dopaminergic neurons – in a specific region of the brain. These nerve cells play an important part in the brain involving the production and release of dopamine. Dopamine release from these cells is critical for normal movement. In the majority of cases, Parkinson’s disease arises spontaneously and why the neurons die is still not known.

What we found and what it meansTreatment with glycyrrhizin had no effect on cell numbers in healthy animals, thus confirming that, by itself, glycyrrhizin is not toxic. MPTP led to a significant reduction of dopaminergic neurons remaining. Although the lower dose of glycyrrhizin was not able to protect against the cell loss, the higher dose did provide protection against MPTP-induced cell death.

What we didFirst, we gave mice MPTP, a chemical neurotoxin which produces the same features as Parkinson’s disease.

AcknowledgementsWith thanks to Rohit Shrivastava and Ross Mounsey, Institute of Medical Sciences, for their help with this project.

Symptoms occurring in Parkinson’s disease (from http://www.doctortipster.com/10064-parkinson-disease-symptoms-and-diagnosis.html)

Neuropathology of Parkinson’s disease. Schematic representation of the (A) normal and (B) diseased nigrostriatal pathway. In Parkinson’s disease, the pathway degenerates, with a marked loss of the dopaminergic neurons that project to the putamen (dashed line) and a much more modest loss of those that project to the caudate (solid line) (adapted from Dauer & Przedboreski, Neuron (2003) 39:889–909).

The most potent treatment for Parkinson’s disease is L-DOPA, a dopamine precursor. By replenishing the brain with dopamine, L-DOPA alleviates almost all Parkinson’s symptoms, but it does lead to side effects that are eventually as debilitating as the disease itself. Therefore a treatment aimed at the main cause of the disease – the degeneration of these neurons – is needed urgently, to enable a later start to the debilitating symptoms and thus an increased quality of life and life expectancy.

We want to establish how to protect these brain cells and thus prevent Parkinson’s disease using a component from licorice. Glycyrrhizin, the main component of liquorice, has been shown to interfere with the pathways leading to cell death, so is capable of protecting cells against neurotoxicity.

The effect of MPTP (lower panel) on dopaminergic neurons in the substantia nigra and the striatum compared with (upper panel) untreated mouse brain.

Then some animals were given glycyrrhizin at different concentrations (16.8mg/kg or 50mg i.p.), with a control group receiving just saline solution. The brains were then deep frozen, sectioned with a cryostat (30µm) and the sections collected and stained for an enzyme called tyrosine-hydroxylase, a specific marker for dopaminergic neurons. These cells were counted using a computer-based counting system. The aim was to clarify whether, if glycyrrhizin did prevent the cells from dying, what concentration would be needed.

Dopaminergic neurons are resistant against MPTP after receiving a high dose (50 mg i.p.) but not a low dose (16.8 mg/kg i.p.) of glycyrrhizin *, P <0.05, compared with MPTP-treated controls (Newman–Keuls posthoc test). Glycyrrhizin, the main compound of liquorice, provides protection in our model of Parkinson’s disease. It might, therefore, be able to provide protection in patients suffering from the disease and lead to a slowing of disease progression.