Ganoderma Triterpenes Retard Renal Cyst Development By Downregulating Ras/MARK Signaling And Promoting Cell Differentiation

- Oct 25, 2018-

Professor Yang Baoxue from Peking University, Researcher Chen Ruoyun from the Chinese Academy of Medical Sciences, and researchers from Harvard Medical School have confirmed that total triterpenes of Ganoderma lucidum can reduce the negative effects of genetic mutations by maintaining the normalization of cells and bring opportunities for the normal life of patients with polycystic kidney disease.

There is an inborn kidney disease that does not occur until the age of forty. Although it will not kill the patient immediately, it will cause the kidney function to be lost bit by bit, and gradually move toward kidney failure. The process could be ten years or twenty years. Most patients are unable to escape hemodialysis or change their kidneys even if they try to control the disease with the medicine.

This is the "autosomal dominant (adult type) polycystic disease", referred to as polycystic kidney or polycystic disease, which is the most common hereditary kidney disease today. Every 400 to 1000 people, one is attacked by this disease.

Mutations in the PKD-1 or PDK-2 genes on the chromosome result in abnormal proliferation of the immature kidney cells, causing the kidneys on both sides to grow many liquid-containing vesicles.

As the vesicles grow larger and more numerous, the compression and destruction to the normal kidney tissues become more serious, and the kidney becomes more difficult to function normally.

Therefore, the primary task in treating this disease is to delay the deterioration of renal function. Unfortunately, the current clinical use of drugs for the delay of renal function degradation has a very limited effect.

Ganoderma lucidum, which has solved many intractable diseases for humans, may also bring new hope for patients with polycystic kidney disease.

Professor Yang Baoxue from Peking University, Researcher Chen Ruoyun from the Chinese Academy of Medical Sciences, and researchers from Harvard Medical School confirmed that the total triterpenoids of Ganoderma lucidum obtained by extracting Ganoderma lucidum with ethanol have the effect in delaying the attack of polycystic kidney disease and reducing the patients' conditions.

The results of this research were published in the Medical Journal of Kidney International in July 2017.

In vitro experiments showed that Reishi Mushroom can effectively inhibit the formation and growth of vesicles in both canine kidney cells and kidneys taken from mouse embryos, and the effect is in direct proportion to the concentration of triterpenoids (6.25, 25, 100 μg/ml), the highest concentration of Ganoderma lucidum can even reduce vesicles by more than half.

The experiment also observed that Ganoderma lucidum triterpenes do not destroy or kill kidney cells, and as long as the Ganoderma lucidum triterpenes are removed, the vesicles will grow up rapidly again.

It can be seen that Ganoderma lucidum triterpenes have considerable security, but they do not have the magical effect once and for all - it must be used all the time to continue to be effective.

In order to bring the experimental results closer to humans, the researchers used two different varieties of "PKD-1 gene-deficient mice" for animal experiments - in fact, the problem of 85% of patients with polycystic kidney disease is in PKD-1 gene.

The first PKD-1 gene-deficient mice began to grow long vesicles from the day of birth and died on average for about 10 days due to kidney failure.

The second PKD-1 gene-deficient mice also developed the disease at birth, but the disease course was slower and the survival time was doubled.

The researchers injected the mice with Ganoderma lucidum triterpenes at its birth, once every 12 hours with each dose of 100 mg/kg. The first group of mice continued to be injected for 4 days while the second group of mice continued to be injected for 8 days.

Comparing the experimental results of these two groups of mice with those of normal mice, and with those of mice with genetic mutations but not given Ganoderma lucidum triterpenes, they found that:

No matter which kind of gene-deficient mice, those injected with Ganoderma lucidum total triterpenoids have a milder kidney enlargement, smaller renal vesicles, and 10 to 20% fewer vesicles distribution area in the kidney. And the structural damage to the kidney tissue is also relatively lighter.

In addition, the researchers also observed the first breed of mice accepting the injection of the same dose of Ganoderma lucidum triterpenoids, which showed no negative effects on the kidneys because their kidney size is not significantly different from that of normal mice that have not been injected with Ganoderma lucidum triterpenes.

Why do Ganoderma lucidum triterpenes inhibit kidney vesicles? It turned out that they reduced the adverse effects of genetic mutations.

Mutations in the two genes, PKD1 and PKD2, increase the concentration of key molecules involved in cell proliferation (such as cAMP) in cells, and the downstream signalling pathways (such as Ras/MAPK) linked to these molecules become abnormally active.

At this time, the kidney cells are in a rapid hyperplasia. Because these hyperplastic cells are very low in differentiation (immature), they also secrete a lot of liquid, so they form something like "vesicles."

According to the analysis of the researchers, Ganoderma lucidum triterpenoids can reduce the concentration of cAMP molecules in kidney cells, inhibit the Ras/MAPK signalling pathway, thereby reducing cell proliferation, and also help kidney cells to differentiate completely and form useful structural tissues(such as renal tubules).

Interestingly, Ganoderma lucidum does not affect the Ras/MAPK signalling pathway in normal kidney cells. 

The Ganoderma lucidum triterpenoids used in the above experiment contains at least 15 triterpenes, and the researchers also found a single triterpenoid compound, ethyl ganoderate C2, which inhibits the activity of renal vesicles.

Unfortunately, the content of this active triterpenoid compound is too low to be used in animal experiments, not to mention clinical application.

Therefore, from the perspective of reality,  Ganoderma lucidum total triterpenes mixed with many ingredients is the current ideal choice for patients for more and better effects.

In their published paper, the researchers mentioned that the pathogenesis of polycystic kidney disease is similar to that of kidney tumours. Many studies have shown that Ganoderma lucidum can fight cancer cells through a variety of mechanisms, and these anti-cancer mechanisms may also contribute to the control of polycystic kidney disease.

Although Ganoderma lucidum cannot change the genetic mutations that are inherent, it can reduce the negative effects of genetic mutations by maintaining the normalization of cells and bring more opportunities of the normal life for patients with polycystic kidney disease.

Just don't forget that the total triterpenes of Lingzhi used in this study are from the alcohol extract of the Ganoderma lucidum fruiting body.  

Data Source: Su L, et al. Ganoderma triterpenes retard renal cyst development by downregulating Ras/MAPK signaling and promoting cell differentiation. Kidney Int. 2017 Jul 11. pii: S0085-2538(17)30301-0.