Artemisinin: From Chinese Herbal Medicine to Modern Chemotherapy

Malaria is a disease that has blighted humankind since early times. The first antimalarial treatment available to Europeans was the dried bark of the cinchona tree from Peru. The main problem in its use was adulteration by other material. The ‘active principle’ was first extracted in 1820 and named quinine. It was found to be a more powerful and reliable drug than cinchona bark. Once its chemical structure had been determined, it was possible to synthesize substances chemically related to quinine that were equally powerful but could be manufactured industrially. Mepacrine (atabrine) was amongst the most successful, but had adverse side effects. To avoid these side effects, further chemical modification gave chloroquine, a highly successful drug. This sequence is a common way of converting an herbal remedy into a modern-style chemical drug. It parallels, to some extent, the process of potentiation common in traditional herbal medicine. By the 1970s, drug resistance had developed with chloroquine. To find and develop a new antimalarial drug that worked on an entirely different pharmacological principle, Chinese scientists turned to their herbal compendia (ben cao) and found that Artemisia annua (qing hao) was frequently mentioned as a treatment for intermittent fever. Whether, in view of the distinctive doctrines of Chinese medicine, it should be possible to extract an active principle as described above is discussed. After a very careful reading of the procedure given for the use of qing hao, an active substance, artemisinin, was extracted. Artemisinin has a truly remarkable chemical structure, and chemical modification produced artesunate, the drug of choice. To prevent the development of resistance, artesunate is used in combination with other antimalarial drugs. Modern pharmacology has largely ignored that other substances in artemisia and the cinchona bark may contribute to their therapeutic effect. This matter is also discussed

Emerg Infect Dis

Artemisinin is an antimalarial lactone derived from qing hao (Artemisia annua or sweet wormwood). The medicinal value of this plant has been known to the Chinese for at least 2,000 years. In 1596, Li Shizhen recommended tea made from qing hao specifically to treat malaria symptoms. The genus name is derived from the Greek god-dess Artemis and, more specifically, may have been named after Queen Artemisia II of Caria, a botanist and medical researcher in the fourth century BCE.2014705

Artemisinin

Malaria is a disease that has blighted humankind since early times. The first antimalarial treatment available to Europeans was the dried bark of the cinchona tree from Peru. The main problem in its use was adulteration by other material. The ‘active principle’ was first extracted in 1820 and named quinine. It was found to be a more powerful and reliable drug than cinchona bark. Once its chemical structure had been determined, it was possible to synthesize substances chemically related to quinine that were equally powerful but could be manufactured industrially. Mepacrine (atabrine) was amongst the most successful, but had adverse side effects. To avoid these side effects, further chemical modification gave chloroquine, a highly successful drug. This sequence is a common way of converting an herbal remedy into a modern-style chemical drug. It parallels, to some extent, the process of potentiation common in traditional herbal medicine. By the 1970s, drug resistance had developed with chloroquine. To find and develop a new antimalarial drug that worked on an entirely different pharmacological principle, Chinese scientists turned to their herbal compendia (ben cao) and found that Artemisia annua (qing hao) was frequently mentioned as a treatment for intermittent fever. Whether, in view of the distinctive doctrines of Chinese medicine, it should be possible to extract an active principle as described above is discussed. After a very careful reading of the procedure given for the use of qing hao, an active substance, artemisinin, was extracted. Artemisinin has a truly remarkable chemical structure, and chemical modification produced artesunate, the drug of choice. To prevent the development of resistance, artesunate is used in combination with other antimalarial drugs. Modern pharmacology has largely ignored that other substances in artemisia and the cinchona bark may contribute to their therapeutic effect. This matter is also discussed

Anti-plasmodial polyvalent interactions in Artemisia annua L. aqueous extract – possible synergistic and resistance mechanisms

Artemisia annua hot water infusion (tea) has been used in in vitro experiments against P. falciparum malaria parasites to test potency relative to equivalent pure artemisinin. High performance liquid chromatography (HPLC) and mass spectrometric analyses were employed to determine the metabolite profile of tea including the concentrations of artemisinin (47.5±0.8 mg L-1), dihydroartemisinic acid (70.0±0.3 mg L-1), arteannuin B (1.3±0.0 mg L-1), isovitexin (105.0±7.2 mg L-1) and a range of polyphenolic acids. The tea extract, purified compounds from the extract, and the combination of artemisinin with the purified compounds were tested against chloroquine sensitive and chloroquine resistant strains of P. falciparum using the DNA-intercalative SYBR Green I assay. The results of these in vitro tests and of isobologram analyses of combination effects showed mild to strong antagonistic interactions between artemisinin and the compounds (9-epi-artemisinin and artemisitene) extracted from A. annua with significant (IC50 <1 μM) anti-plasmodial activities for the combination range evaluated. Mono-caffeoylquinic acids, tri-caffeoylquinic acid, artemisinic acid and arteannuin B showed additive interaction while rosmarinic acid showed synergistic interaction with artemisinin in the chloroquine sensitive strain at a combination ratio of 1:3 (artemisinin to purified compound). In the chloroquine resistant parasite, using the same ratio, these compounds strongly antagonised artemisinin anti-plasmodial activity with the exception of arteannuin B, which was synergistic. This result would suggest a mechanism targeting parasite resistance defenses for arteannuin B’s potentiation of artemisinin

Ancient Chinese methods are remarkably effective for the preparation of artemisinin-rich extracts of Qing Hao with potent antimalarial activity.

yesAncient Chinese herbal texts as far back as the 4th Century Zhou hou bei ji fang describe methods for the use of Qing Hao (Artemisia annua) for the treatment of intermittent fevers. Today, the A. annua constituent artemisinin is an important antimalarial drug and the herb itself is being grown and used locally for malaria treatment although this practice is controversial. Here we show that the ancient Chinese methods that involved either soaking, (followed by wringing) or pounding, (followed by squeezing) the fresh herb are more effective in producing artemisinin-rich extracts than the usual current method of preparing herbal teas from the dried herb. The concentrations of artemisinin in the extracts was up to 20-fold higher than that in a herbal tea prepared from the dried herb, but the amount of total artemisinin extracted by the Chinese methods was much less than that removed in the herbal tea. While both extracts exhibited potent in vitro activities against Plasmodium falciparum, only the pounded juice contained sufficient artemisinin to suppress parasitaemia in P. berghei infected mice. The implications of these results are discussed in the context of malaria treatment using A. annua infusions

Thermoelectricity in Nanowires: A Generic Model

By employing a Boltzmann transport equation and using an energy and size dependent relaxation time ($\tau$) approximation (RTA), we evaluate self-consistently the thermoelectric figure-of-merit $ZT$ of a quantum wire with rectangular cross-section. The inferred $ZT$ shows abrupt enhancement in comparison to its counterparts in bulk systems. Still, the estimated $ZT$ for the representative Bi$_2$Te$_3$ nanowires and its dependence on wire parameters deviate considerably from those predicted by the existing RTA models with a constant $\tau$. In addition, we address contribution of the higher energy subbands to the transport phenomena, the effect of chemical potential tuning on $ZT$, and correlation of $ZT$ with quantum size effects (QSEs). The obtained results are of general validity for a wide class of systems and may prove useful in the ongoing development of the modern thermoelectric applications.Comment: 15 pages, 6 figures; Dedicated to the memory of Amirkhan Qezell