Cordyceps Sinensis: Not All Species Have Anti-Cancer Properties

January 2, 2024

Dongchongxiacao has always been a legendary traditional Chinese medicine with not only strong nourishing effects but also the potential to fight against cancer. However, the latest research indicates that not all species of Cordyceps sinensis have anti-cancer properties.


On the evening of the 19th, Dr. Wang Chengshu, a researcher at the Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, led his research team to publish a paper online in the international academic journal "Cell Chemical Biology", announcing that Cordyceps sinensis does not contain cordycepin, and this is determined by genetics.

"Because there is no cordycepin synthesis gene in Cordyceps sinensis, and it is also absent in Cicada flower," said Wang Chengshu.

【The clinical trial of the star molecule cordycepin has not been completed】

Cordycepin has been a star molecule, frequently appearing in advertisements, but it has also been subject to lawsuits and doubts due to a lack of sufficient clinical trial evidence. So far, the food and drug regulatory authorities have not approved cordycepin for sale as a medication.

The research on cordycepin can be traced back to 1950. In December of that year, German scientists published a paper in "Nature" for the first time, discovering cordycepin. However, for nearly 70 years, people have been unaware of how it is synthesized.

Cordyceps militaris contains cordycepin. When Wang Chengshu's research team was studying the synthesis pathway of cordycepin, they made an unexpected discovery. They found an anti-cancer active ingredient called "pentostatin" in Cordyceps militaris. As early as 1991, "pentostatin" was approved by the US Food and Drug Administration (FDA) as an anti-leukemia drug and was launched in the United States. The product is mainly produced through chemical synthesis.

The presence of "pentostatin" indicates that Cordyceps militaris has certain anti-cancer functions. Unfortunately, Cordyceps sinensis and Cicada flower do not contain cordycepin or "pentostatin."

Currently, more than 1500 species of Cordyceps have been discovered by humans. Wang Chengshu's research team has conducted genomic research on 18 of them. They found that only Cordyceps militaris and Cordyceps kyushuensis contain "pentostatin" and cordycepin.

In addition, a fungus called Metarhizium anisopliae can also produce "pentostatin" and cordycepin. In the wild, Cordyceps sinensis may be contaminated with this fungus, resulting in trace amounts of cordycepin.


【But Cordyceps sinensis should not be dismissed altogether】

Wang Chengshu stated that they have discovered more than 20 genes in the genome of Cordyceps sinensis that may be involved in the synthesis of active substances. However, the functions of these genes are still unknown.

After 7 years of research, they found the synthesis pathway of the anti-cancer ingredient "pentostatin". "Pentostatin" can be used as a molecular indicator to evaluate the quality of Cordyceps militaris.

Wang Chengshu stated that the clarity of active ingredients and molecular indicators is one of the challenges that traditional Chinese medicine faces when entering the international market. Apart from the recorded efficacy in traditional Chinese medicine literature, there are still many unknown functions and new active ingredients waiting to be discovered, which is like finding a gold mine.

"Pentostatin" and cordycepin always appear together. Further research confirmed that "pentostatin" acts as a protective umbrella for cordycepin. Without "pentostatin," cordycepin will be degraded.

Wang Chengshu revealed that as early as 2011, they sequenced the genome of Cordyceps militaris and published related papers. But in order to understand the synthesis pathway of cordycepin and "pentostatin," they spent nearly 7 years of research.

At the time of the publication of this latest paper, one of the former doctoral students of the research team had already graduated and is currently studying abroad.


【Do not consume cordycepin excessively】

Wang Chengshu said that from treating malaria with Artemisia annua to discovering artemisinin, from Cordyceps militaris to discovering "pentostatin," this is the inner strength that pharmaceutical researchers need to cultivate.

Wang Chengshu stated that they have applied for patent protection for the genes involved in the synthesis pathway of "pentostatin" and cordycepin. In the future, these genes may be applied in synthetic biology, using other bacteria or plants to produce "pentostatin" and cordycepin.

In addition, Wang Chengshu reminded that when consuming cordycepin, it should not be excessive. The molecular structure of cordycepin is very similar to adenine nucleotides. Once phosphorylated cordycepin is incorporated into the synthesis process of human DNA or RNA, it may cause genetic mutations or functional loss. This is the mechanism of its anti-cancer effects, but it may also have negative effects on rapidly proliferating cells in the human body. In Cordyceps militaris, researchers observed that the fungus degrades excessive cordycepin.

Wang Chengshu speculates that "pentostatin" and cordycepin are the "weapons" for Cordyceps militaris to adapt to the environment and fight against other microorganisms in the wild.

They found that when Cordyceps militaris grows on silkworm pupae, it produces the highest amount of "pentostatin." When it grows on rice, the amount decreases, and when cultured in liquid medium, the amount is the lowest. The molecular mechanism behind this phenomenon is still unclear. Currently, the annual production of Cordyceps militaris is about 1000 tons by cultivating it on rice.

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