April 25 is World Malaria Day. Speaking of malaria, people naturally think of artemisinin and its discoverer Tu Youyou.
This year coincides with the 50th anniversary of artemisinin. Once, people talked about “malaria” discoloration. Some figures show that before the discovery of artemisinin, about 400 million people were infected with malaria every year in the world, and at least 1 million people died of the disease.
On June 30, 2021, the World Health Organization announced that China has passed the certification of malaria elimination. From the 1940s, when about 30 million malaria cases were reported each year to today’s complete elimination, it’s a remarkable feat. In the world, malaria is still endemic in 91 countries and regions, and the most serious region is sub-Saharan Africa, accounting for 90% of the global proportion. But global malaria mortality rates have halved since 2000. Among them, artemisinin, “China’s magic grass”, has contributed a lot.
Artemisinin-based antimalarial drugs are a gift from traditional Chinese medicine to the world
Since the advent of artemisinin in the 1970s, countless malaria patients have been cured. Artemisinin-type antimalarial drugs have become life-saving drugs in malaria-stricken areas.
“This is a gift from traditional Chinese medicine to the world,” said Tu Youyou, a lifelong researcher and chief researcher at the China Academy of Traditional Chinese Medicine and director of the Artemisinin Research Center.
The story of Tu Youyou and artemisinin is well known in China and around the world. For half a century, artemisinin, dihydroartemisinin, compound artemether, dihydroartemisinin piperaquine tablets… Artemisinin and its derivatives have been widely used in antimalarial clinics and have gone abroad. ultimately affected the world.
However, Tu Youyou always kept these words on her lips: “Artemisinin is the result of a national system. In the battle of global malaria prevention and control, the power of individuals is insignificant, and only organized and Malaria can only be gradually defeated by a large team of targets.”
Liao Fulong, a colleague of Tu Youyou and a researcher at the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, also believes that the discovery of artemisinin reflects not only the role of Chinese medicine in international medical and health care An original in the field reflects the spiritual outlook of a generation of Chinese researchers, that is, their responsibility and responsibility for national tasks.
“Now this spirit has been summed up as the ‘artemisinin spirit’: cherish the motherland, dare to take responsibility, unite and cooperate, inherit and innovate, love the common people, indifferent to fame and fortune, enhance self-confidence, and bravely climb the peak.” Liao Fulong said.
Research progress on artemisinin resistance and other indications
It goes without saying that after half a century, artemisinin has played an important role in the global malaria control, but its role in the treatment of malaria has not been neglected. The underlying mechanisms remain obscure. In particular, the resistance to artemisinin has always been a concern of Tu Youyou, and it is also the biggest challenge facing the global anti-malarial.
It is in this spirit that Tu Youyou and her team members have been working hard. “What we have been doing is to find out the mechanism of action of artemisinin, crack its drug resistance, and how to expand the indications of artemisinin drugs.” Liao Fulong said.
To my delight, on June 17, 2019, Tu Youyou’s team announced that their 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 activation of artemisinin, and found that the activated artemisinin can covalently bind to more than 100 proteins of Plasmodium Bonding and alkylation, destroying many life processes of the malaria parasite, thereby killing the malaria parasite. This multi-target theory of heme activation has been recognized by the international antimalarial community, which is of great significance for revealing the underlying mechanism of artemisinin antimalarial, drug resistance and promoting more effective clinical drugs.
Wang Jigang introduced that according to research, the half-life of artemisinin in the human body is very short, only 1 to 2 hours, while the clinically recommended artemisinin combination therapy (ACT) course of treatment is 3 days. There is only a limited 4 to 8 hours window for truly efficient insecticidal activity. However, the existing drug-resistant insect 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, malaria parasites can also produce obvious drug resistance to the adjuvant drug “antimalarial formula” in artemisinin combination therapy, making artemisinin combination therapy “ineffective”.
In response to this, the team proposed a new treatment plan: one is to appropriately extend the medication time from 3-day therapy to 5-day or 7-day therapy; Resistant adjunctive drugs. “In the foreseeable future, the continued rational and strategic application of artemisinin combination therapy is the best solution to treatment failure, and it may be the only solution.” Wang Jigang emphasized.
In addition to the antimalarial research of artemisinin, the team is also very concerned about the anticancer effects of artemisinin. The anticancer mechanism of artemisinin is similar to the antimalarial mechanism, that is, compared with normal somatic cells, the synthesis of heme in tumor cells is more vigorous, which activates artemisinin or its derivatives, and then activates artemisinin. It kills tumor cells in a multi-target manner. However, team members said that the anti-cancer efficacy of artemisinin is still in the basic research stage, and effectiveness does not mean that it can be turned into a medicine. Whether artemisinin can become an anticancer drug still needs a lot of follow-up research work.
Then there is much 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. “Under the auspices of Kunpharm Group, a Phase II clinical trial is currently underway, and it is expected that the blinding can be opened in September.” Liao Fulong said that previous trials have shown that artemisinin has a trend of effectiveness in the treatment of lupus erythematosus. However, the mechanism of action of dihydroartemisinin in the treatment of lupus erythematosus remains to be further studied.