Artemisinin: "Chinese God Grass" refines the global antimalarial medicine

More than 100

Activated artemisinin can covalently bond with more than 100 proteins of malaria parasites and alkylate them, destroying many life processes of malaria parasites, thereby killing the parasites

This is a gift of Chinese medicine to the world, and it is also a vivid practice of Chinese medicine modernization

Malaria is one of the important public health issues of global concern

Since the advent of artemisinin in the 1970s, countless malaria patients have been cured

The hardships behind it can only be experienced by those who have experienced it

The discovery of artemisinin saved millions of lives

However, she always said: "In the global battlefield of malaria prevention and control, individual strength is small, and only organized and targeted large teams can gradually defeat malaria

Indeed, artemisinin is the result of the nationwide system

After all the hardships, the effective components of Artemisia annua L.

Tu Youyou was born in Ningbo, Zhejiang.

On the eve of the university entrance examination in 1951, Tu Youyou reported to the Department of Pharmacy of Peking University School of Medicine

At the end of January 1969, Tu Youyou, a 39-year-old former intern researcher at the Institute of Traditional Chinese Medicine of the Ministry of Health, suddenly received a secret task-the "523" task: as the leader of the research team, research and development of anti-malarial Chinese herbal medicine

After taking over the task, Tu Youyou read through ancient books, searched for prescriptions, visited old Chinese medicine doctors, and copied the information on Chinese medicines verbatim

By the beginning of September 1971, the research group had screened more than 200 samples of water extracts and alcohol extracts of more than 100 kinds of traditional Chinese medicine, but the results were disappointing

"I also doubt if I took the wrong path, but I don't want to give up

From "Shen Nong's Materia Medica" to "Sheng Ji Zong Lu" to "Febrile Diseases".

Why did the ancients use "juice"? Did heating destroy the active ingredients in Artemisia annua? Tu Youyou decided to use ether with a boiling point of only 34.
6°C to extract Artemisia annua
.
"We bought A.
annua, soaked first, then wrapped the leaves and soaked in ether.
It wasn't until the No.
191 extract that we really found the effective components
.
" Tu Youyou said
.

The experiment process is complicated and lengthy
.
On October 4, 1971, the animal anti-malarial experiment of the neutral extract of Artemisinol 191 was finally released-the inhibition rate of malaria parasite reached 100%
.

Researchers tried artemisinin by themselves

In March 1972, Tu Youyou reported 100% inhibition rate of mouse malaria and monkey malaria by neutral crude extracts of artemisinin at a meeting of the Nanjing Traditional Chinese Medicine Professional Group hosted by the "523" Office
.

The "523" office requested that he had to go to the clinic in Hainan that year to see how the effect was
.

In the pre-clinical test of extract No.
191, suspected side effects were found in the pathological sections of individual animals
.
Is it a problem with the animal itself, or is it caused by the drug? Colleagues engaged in toxicology and pharmacological experiments insist: Only after conducting follow-up animal experiments and ensuring safety can they go to the clinic
.

"I am the team leader, and I am responsible for the first test drug!" In order not to miss the clinical observation season that year, Tu Youyou submitted a voluntary test drug report to the leader
.
In July 1972, Tu Youyou and three other scientific researchers were admitted to Beijing Dongzhimen Hospital.
After a week of testing and observation, the extract was not found to have obvious toxic and side effects on the human body
.

With the ether neutral extract of Artemisia annua, Tu Youyou and others went to the Changjiang area of ​​Hainan for clinical verification
.
The results show that the drug has a certain effect on vivax malaria and falciparum malaria in local, low malaria areas, and foreign populations, especially for 11 patients with vivax malaria, with an effective rate of 100%
.

Subsequently, the first task of the research group was to find the effective ingredients in the neutral extract of artemisinin as soon as possible
.
In November 1972, based on the pretreatment of the chromatographic column by the team member Ni Muyun, Zhong Yurong used silica gel column to separate and eluted with petroleum ether and ethyl acetate-petroleum ether, and finally obtained the effective monomer artemisinin with antimalarial effect.

.
Artemisinin was born
.

"Obtaining effective ingredients is only the first step, and clinical trials must be carried out before application.
This requires a large amount of artemisinin
.
" Jiang Tingliang, a member of the research team, recalled that the research team was "initiated by local methods": using 7 water tanks used by ordinary people.
As a conventional extraction container in the laboratory, it is filled with ether, and the Artemisia annua L.
is soaked in it for extraction
.

The equipment is simple, there is no ventilation system, and no protective equipment.
In addition to dizziness and swelling, the researchers also have symptoms such as nose bleeding and skin allergies.
Tu Youyou also developed toxic hepatitis
.

However, they did not stop at artemisinin
.
In 1973, the research team also discovered for the first time an artemisinin derivative with better curative effect—dihydroartemisinin
.
This is another important contribution made by Tu Youyou and his research team to China and the world
.

Artemisinin antimalarial drugs are the result of the nationwide system, the crystallization of collectivism, and a masterpiece of independent innovation
.
Tu Youyou often emphasized that honor belongs to everyone in the scientific research team and belongs to the group of Chinese scientists
.

After nearly half a century, the research of artemisinin continues to move forward

Nowadays, it has been nearly half a century since artemisinin was discovered.
Artemisinin and its derivatives have entered the international antimalarial clinic and become the first-line antimalarial drugs in the world
.

Needless to say, artemisinin has contributed to the global malaria prevention and treatment, but its underlying mechanism for the treatment of malaria is still unclear
.
In particular, the resistance of artemisinin is an issue that Tu Youyou has always been concerned about, and it is also the biggest challenge facing the global fight against malaria
.

Fortunately, on June 17, 2019, Tu Youyou team announced that its artemisinin resistance research has made phased progress
.
Wang Jigang, a member of Tu Youyou's team and a researcher at the Artemisinin Research Center of the Chinese Academy of Chinese Medical Sciences, used chemical biology methods to study the process of heme activating artemisinin and found that the activated artemisinin can covalently covalently with more than 100 proteins of Plasmodium Bonds and alkylates them, destroying many life processes of the malaria parasite, thereby killing the parasite
.
This heme-activated multi-target theory has been recognized by the international antimalarial community, and is of great significance for revealing the deep-seated mechanism of artemisinin antimalarial, drug resistance, and promoting more effective clinical medication
.

According to Wang Jigang, according to research, the half-life of artemisinin in the human body is very short, only 1 to 2 hours, while the clinical recommended artemisinin combination therapy course is 3 days, and the really effective insecticidal window of artemisinin is only limited.
To 8 hours
.
The existing drug-resistant strains make full use of the short half-life of artemisinin to change the life cycle or temporarily enter a dormant state to avoid the sensitive insecticidal period
.
At the same time, the malaria parasite can also develop significant resistance to the adjuvant drug "anti-malarial formula" in the artemisinin combination therapy, making the artemisinin combination therapy "failure"
.

In response to this, the team proposed a new treatment plan: one is to appropriately extend the medication time from 3 days to 5 or 7 days; the other is to replace the adjuvant drugs that have developed resistance in the artemisinin combination therapy
.
"In the foreseeable future, continuing to rationally and strategically apply artemisinin combination therapy (ACT) is the best solution to treatment failure, and it may also be the only solution
.
" Wang Jigang emphasized
.

In addition to the anti-malarial research of artemisinin, the team also paid close attention to the anti-cancer effects of artemisinin
.
The anti-cancer mechanism of artemisinin is similar to the anti-malarial mechanism, that is, compared with normal body cells, the synthesis of heme in tumor cells is more vigorous, which activates artemisinin or its derivatives, and then activates the artemisinin It kills tumor cells in a multi-target manner
.
However, team members said that the anti-cancer effect of artemisinin is still in the basic research stage, and its effectiveness does not mean that it can be made into medicine
.
Whether artemisinin can become an anticancer drug requires a lot of follow-up research work
.

Then there is the concern about artemisinin-based drugs in the treatment of lupus erythematosus
.
Dihydroartemisinin has a unique effect on the treatment of lupus erythematosus with high variability
.
Phase II clinical trials have been carried out
.
Tests have shown that artemisinin has an effective trend in the treatment of lupus erythematosus
.
In this regard, team members also said that the mechanism of action of dihydroartemisinin in the treatment of lupus erythematosus remains to be further studied
.