April 2019 / Xuanwu Hospital, Capital Medical University, Beijing / Acta Pharmacologica Sinica

Text/Wu Tingyao

Does Ganoderma lucidum contribute to patients with Parkinson’s disease (PD)?
A team led by Chen Biao, professor of neurology and director of Parkinson’s Disease Research, Diagnose and Treatment Center at Xuanwu Hospital, Capital Medical University, Beijing, published a research report in Acta Pharmacologica Sinica (Chinese Journal of Pharmacology) in April 2019. It is worthy of your reference.
Seeing the potential of Ganoderma lucidum to improve Parkinson’s disease from clinical trials and cell experiments

The research team stated in this report that they had previously observed the efficacy of Ganoderma lucidum extract in 300 patients with Parkinson’s disease in a randomized, double-blind, placebo-controlled clinical trial: the subject’s course of disease from the first phase (the symptoms appear on one side of the body) to the fourth phase (the patient needs help in daily life but can walk on his own). After two years of follow-up, it is found that oral administration of 4 grams of Ganoderma lucidum extract per day can slow down the deterioration of the patient’s dyskinesia. Although the results of this research have not been published, it has already given the research team a glimpse of certain possibilities of Ganoderma lucidum in patients.
In addition, they have previously found in cell experiments that Ganoderma lucidum extract can inhibit the activation of microglia (immune cells in the brain) and avoid damage to dopamine neurons (nerve cells that secrete dopamine) by excessive inflammation. This research result was published in “Evidence-Based Complementary and Alternative Medicine” in 2011.
The massive death of dopamine neurons in substantia nigra is the cause of Parkinson’s disease, because dopamine is an indispensable neurotransmitter for the brain to regulate muscle activity. When the amount of dopamine is reduced to a certain level, patients will begin to experience typical Parkinson’s symptoms such as involuntary shaking of hands and feet, stiff limbs, slow movement, and unstable posture (easy to fall due to loss of balance).
Therefore, the above experiments show that Ganoderma lucidum extract has the effect of protecting dopamine neurons, which must be of certain significance for Parkinson’s disease. Whether such a protective effect can be established in the body, and what mechanism of action Ganoderma lucidum uses to protect dopamine neurons is the focus of the research team in the published report.
Mice with Parkinson’s disease that eat Ganoderma lucidum have slower limb motor degeneration.

The Ganoderma lucidum used in the experiment is a preparation made of Ganoderma lucidum fruiting body extract, which contains 10% polysaccharides, 0.3-0.4% ganoderic acid A and 0.3-0.4% ergosterol.
The researchers first injected the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) into the mice to induce symptoms similar to Parkinson’s disease and then treated the mice with daily intragastric administration of 400 mg/kg Ganoderma lucidum extract. After four weeks, the mice were assessed for their ability to regulate limb movement by the balance beam walking test and the rotarod test.
The results showed that compared to mice with Parkinson’s disease that were not protected by Ganoderma lucidum, mice with Parkinson’s disease that ate Ganoderma lucidum can pass the balance beam faster and continue to run on the rotarod for a longer time, especially approximate to the control group of normal mice in the rotarod test (Figure 1). These results all show that continuous use of Ganoderma lucidum extract can alleviate limb movement disorder caused by Parkinson’s disease.

Figure 1 The effect of eating Ganoderma lucidum for four weeks on the limb movement of mice with Parkinson’s disease

Beam walking task
The beam walking task consisted of placing the mouse on a suspended (50 cm above the floor), narrow wooden beam (100 cm long, 1.0 cm wide, and 1.0 cm tall). During training and testing, the mouse was placed at the starting zone facing its home cage, and a stopwatch started immediately upon release of the animal. Performance was assessed by recording the animal’s latency to traverse the beam.
Rotarod task
In the rotarod task, the parameters were set as follows: initial speed, five revolutions per minute (rpm); maximum speed, 30 and 40 rpm over the course of 300 s. The duration that the mice remained on the rotarod was automatically recorded.
Mice with Parkinson’s disease that eat Ganoderma lucidum have a milder loss of dopamine neurons.

In the analysis of the brain tissue of the above experimental mice, it was found that the number of dopamine neurons in the substantia nigra pars compacta (SNpc) or striatum of the mice with Parkinson’s disease who had been fed Ganoderma lucidum was double or even more than that of the diseased mice without Ganoderma lucidum protection (Figure 2).
The dopamine neurons of the substantia nigra tissue of the brain are mainly concentrated in the substantia nigra pars compacta, and the dopamine neurons here also extend to the striatum. Dopamine from the substantia nigra pars compacta is transmitted to the striatum along this path, and then further transmits the message of regulating movement downward. Therefore, the number of dopamine neurons in these two parts is very important for the development of Parkinson’s disease.
Obviously, the experimental results in Figure 2 show that for the mice with Parkinson’s disease, the Ganoderma lucidum extract can protect the dopamine neurons of the substantia nigra pars compacta and the striatum at the same time. And this protective effect also explains to some extent why mice with Parkinson’s disease that eat Ganoderma lucidum have better motor ability.

Figure 2 The effect of eating Ganoderma lucidum for four weeks on dopamine neurons in the brains of mice with Parkinson’s disease

[Note] Figure C shows the staining of a mouse brain tissue section. The colored parts are dopamine neurons. The darker the color, the greater the number of dopamine neurons. Figures A and B are based on Figure C to quantify dopamine neurons.

Ganoderma lucidum protects the survival of nerve cells and maintains the function of mitochondria

In order to understand how Ganoderma lucidum extract protects dopamine neurons, the researchers further analyzed it through cell experiments. It was found that co-culturing the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and mouse nerve cells caused not only a large number of nerve cells to die but also mitochondrial dysfunction within the cells (Figure 3).
Mitochondria are called “cell generators”, the energy source of cell operation. When the mitochondria fall into the crisis of dysfunction, not only the energy (ATP) produced is sharply reduced, but more free radicals are emitted, which accelerates the aging and death of cells.
The above-mentioned problems will become more serious with the lengthening of MPP+ action time, but if Ganoderma lucidum extract is added to it at the same time, it can offset partial lethality of MPP+, and retain more nerve cells and normal functioning mitochondria (Figure 3).

Figure 3 The protective effect of Ganoderma lucidum on mouse nerve cells and mitochondria

[Note] Figure A shows the death rate of mouse nerve cells cultured in vitro. The longer the action time of the neurotoxin MPP+ (1 mM), the higher the death rate. However, if Ganoderma lucidum extract is added (800 μg/mL), the cell death rate will be greatly reduced.

Picture B is the mitochondria in the cell. The red fluorescent is the mitochondria with normal function (normal membrane potential), and the green fluorescent is the mitochondria with impaired function (decreased membrane potential). The more and stronger the green fluorescence, the more the abnormal mitochondria.

The possible mechanism by which Ganoderma lucidum protects dopamine neurons

Many abnormal proteins that accumulate in the substantia nigra of the brain cause the death of a large number of dopamine neurons, which is the most important pathological feature of Parkinson’s disease. How these proteins cause the death of dopamine neurons, although it has not been completely clarified, it is known to be closely related to the “mitochondrial dysfunction” and “oxidative stress increase” in nerve cells. Therefore, the protection of mitochondria becomes an important key to delaying the deterioration of the disease.
Researchers said that many studies in the past have said that Ganoderma lucidum protects nerve cells through antioxidant mechanisms, and their experiments have observed that Ganoderma lucidum extract can maintain the function and quality of mitochondria under the premise of external interference so that dysfunctional mitochondria will not accumulate too much in nerve cells and shorten the lifespan of nerve cells; on the other hand, Ganoderma lucidum extract can also prevent the mechanism of apoptosis and autophagy from being activated, reducing the chance that nerve cells will kill themselves due to external stress.
It turns out that Ganoderma lucidum can protect dopamine neurons in a multi-pronged way, allowing them to survive under the attack of toxic proteins.
In addition, the researchers also observed in the brain nerve cells of newborn mouse babies that the neurotoxin MPP+ will greatly reduce the mobility of mitochondria in the axons, but if it is protected by Ganoderma lucidum extract at the same time, the movement of mitochondria will be more agile.
Nerve cells are different from ordinary cells. In addition to the cell body, it also grows long “tentacles” from the cell body to transmit the chemical substances secreted by the cell body. When the mitochondria move faster, the transmission process will be smoother. This is probably another reason why patients or mice with Parkinson’s disease who eat Ganoderma lucidum can maintain better exercise ability.

Ganoderma lucidum helps patients coexist peacefully with Parkinson’s disease

At present, there is no medicine that can reverse the course of Parkinson’s disease. People can only try to delay the deterioration of the disease while maintaining the function of mitochondria in nerve cells is considered a feasible adaptive strategy.
There are many similarities between the neurotoxins used in the above-mentioned animal experiments and cell experiments and the toxic protein that induces Parkinson’s disease in humans in their mechanism of harming dopamine neurons. Therefore, the effect of Ganoderma lucidum extract in the above experiments is probably the way Ganoderma lucidum extract protects patients with Parkinson’s disease in clinical practice, and the effect can be achieved by “eating”.
However, just like the results seen in humans, animals and cells, Ganoderma lucidum helps delay the deterioration of the disease rather than eliminate the disease. Therefore, the role of Ganoderma lucidum extract in Parkinson’s disease should not be a momentary encounter but a long-term companionship.
Since we can’t end the disease, we can learn to live with it and reduce its interference with our bodies and lives. This should be the significance of Ganoderma lucidum for Parkinson’s disease.
[Source] Ren ZL, et al. Ganoderma lucidum extract ameliorates MPTP-induced parkinsonism and protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis. Acta Pharmacol Sin. 2019 Apr;40(4):441-450.
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About the author/ Ms. Wu Tingyao
Wu Tingyao has been reporting on first-hand Ganoderma information since 1999. She is the author of Healing with Ganoderma (published in The People’s Medical Publishing House in April 2017).

★ This article is published under the exclusive authorization of the author. 

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★ The original text of this article was written in Chinese by Wu Tingyao and translated into English by Alfred Liu. If there is any discrepancy between the translation (English) and the original (Chinese), the original Chinese shall prevail. If readers have any questions, please contact the original author, Ms. Wu Tingyao.