The present work aimed at studying the efficacy of mebendazole (MBZ) compared to artemisinin (ART) for the treatment of trichinellosis at various phases of infection. Seventy Swiss albino mice were orally infected by 300 Trichinella spiralis (T. spiralis) larvae. Mice were divided into infected untreated control group and infected groups treated with 50 mg kg−1 MBZ and 300 mg kg−1 ART for three and five consecutive days, respectively, at the enteral phase [2–4 days post infection (PI)], invasive phase (10–12 days PI) and encapsulated phase (28–30 days PI). All mice were sacrificed 35–42 days PI. MBZ and ART revealed a significant decrease in mean larval counts and increase of larval per cent reduction (LR %) when treatment was initiated during the enteral phase compared to the other phases. MBZ showed significantly higher LR % (99.7, 83.95 and 89.65%) than ART (80.58, 67.0 and 79.2%) when administered at the three infection phases. Histopathological study showed a decrease in the number of encysted larvae, their surrounding cellular infiltrates and increased regenerative muscles in all treated mice. In conclusion, ART possesses a substantial anthelmintic activity against T. spiralis infection in mice both at the enteral and encapsulated phases, yet, significantly lower than MBZ.

Endoperoxides kill malaria parasites via cleavage of their endoperoxide bridge by haem or iron, leading to generation of cytotoxic oxygen-centred radicals. In view of the Leishmania parasites having a relatively compromised anti-oxidant defense and high iron content, this study aims to establish the underlying mechanism(s) accounting for the apoptotic-like death of Leishmania promastigotes by artemisinin, an endoperoxide. The formation of reactive oxygen species was confirmed by flow cytometry and was accompanied by inhibition of mitochondrial complexes I–III and II–III. However, this did not translate into a generation of mitochondrial superoxide or decrease in oxygen consumption, indicating minimal impairment of the electron transport chain. Artemisinin caused depolarization of the mitochondrial membrane along with a substantial depletion of adenosine triphosphatase (ATP), but it was not accompanied by enhancement of ATP hydrolysis. Collectively, the endoperoxide-mediated radical formation by artemisinin in Leishmania promastigotes was the key step for triggering its antileishmanial activity, leading secondarily to mitochondrial dysfunction indicating that endoperoxides represent a promising therapeutic strategy against Leishmania worthy of pharmacological consideration.

The field of Traditional Chinese Medicine (TCM) represents a vast and largely untapped resource for modern medicine. Exemplified by the success of the antimalarial artemisinin, the recent years have seen a rapid increase in the understanding and application of TCM-derived herbs and formulations for evidence-based therapy. In this review, we summarise and discuss the developmental history, clinical background and molecular basis of an action for several representative TCM-derived medicines, including artemisinin, arsenic trioxide, berberine and Salvia miltiorrhiza or Danshen. Through this, we highlight important examples of how TCM-derived medicines have already contributed to modern medicine, and discuss potential avenues for further research.

Annual wormwood has been cultivated on a small scale for production of the artemisinin class of antimalarial drugs in sufficient quantities for preclinical and clinical trials. Large scale cultivation will require a reliable, efficient crop production system. Production systems using 32 herbicides alone or in combinations were evaluated in growth chamber, greenhouse, and field experiments at Stoneville, MS from 1985 through 1988. The herbicide treatments that provided the best weed control were (A) metolachlor at 2.2 kg ai ha-1 preemergence (PRE), (B) chloramben at 2.2 kg ai ha-1 (PRE), or (C) trifluralin at 0.6 kg ai ha-1 preplant soil incorporated (PPI) followed by fluazifop at 0.2 + 0.2 kg ai ha-1 postemergence broadcast (POST) and acifluorfen at 0.6 kg ai ha-1 (POST). These herbicide production systems provided excellent weed control (≥85%) and minimal crop injury (≤10%) with no effect on crop height or weight at harvest. Production of artemisinin was not reduced by herbicide treatments A, B, and C in 1987 and treatments B and C in 1988 when compared with the hand-weeded plots.

One of the big success stories in synthetic biology is the re-engineering of an existing organism to produce the anti-malarial drug artemisinin. The drug is also found naturally in extracts of the plant Artemisia annua (Wormwood), but demand is far oustripping supply and extracting the drug from the plants is complex, time-consuming and expensive. In this lecture, Jay Keasling describes how he and his laboratory re-designed yeast microbes into living mini anti-malaria drug factories producing artemisinin more cheaply and efficiently. The lecture was given at the 12 May 2009 launch of the Imperial-based Centre for Synthetic Biology and Innovation—established in partnership with the London School of Economics and funded by the Engineering and Physical Sciences Research Council (EPSRC) as part of a science and innovation award.

Guidelines recommend praziquantel (PZQ) for the treatment and control of schistosomiasis, with no real alternative. Metrifonate was still widely used against Schistosoma haematobium in the 1990s, and then withdrawn. Experimental studies and clinical trials suggest that artemisinin compounds are active against S. haematobium. In a Cochrane systematic review assessing the efficacy and safety of drugs for treating urinary schistosomiasis, 24 randomized controlled trials (n=6315 individuals) met our inclusion criteria. These trials compared a variety of single agent and combination regimens with PZQ, metrifonate or artemisinin derivatives. The review confirmed that both the standard recommended doses of PZQ (single 40 mg/kg oral dose) and metrifonate (3×7·5–10 mg/kg oral doses administered fortnightly) are efficacious and safe in treating urinary schistosomiasis, but there is no study comparing these two regimens head-to-head. There is currently not enough evidence to evaluate artemisinin compounds. Most of the studies included in the Cochrane systematic review were insufficiently powered, lacked standardization in assessing and reporting outcomes, and had a number of methodological limitations. In this paper we discuss the implications of these findings with respect to public health and research methodology and propose priority research needs.

We have investigated the effect of qinghaosu (QHS, artemisinin) and its derivatives on Leishmania major replication in vitro and on the disease development in mice infected with L. major. Artemisinin is effective against promastigotes in vitro, with an ED 50 (50% effective dose) at 7.5 × 10−7 m. Both artemisinin and artemether are leishmanicidal for amastigotes in infected murine macrophages in vitro, with ED50 at 3 × 10−5 m and 3 × 10−6 m respectively. These compounds have no effect on the viability of macrophages or on the phytohaemaglutinin-induced proliferation of normal spleen cells, even at 10−4 m. BALB/c mice infected in the footpad with L. major developed significantly smaller lesions and parasite loads when treated with the compounds. Intra-lesion injection of the compounds was the most effective route. The intramuscular and oral routes were also effective; however, intravenous injection with artesunate was not effective.

Malaria has been treated for over 350 years with quinine and quinine-derived drugs. However, in several areas of the world, some strains of the malarial parasite Plasmodium falciparum have developed resistance against these drugs. Recently, the World Health Organization (WHO) recommended the use of artemisinin-combination treatments (ACT) as the first-line treatment for multidrug-resistant falciparum malaria. The WHO estimates that current supplies of artemisinin are sufficient for only 30 million ACT, and is foreseeing the need for 130–220 million ACT in 2005 (WHO, 2004). Current research on the production of synthetic artemisinin-like compounds by the Roll Back Malaria project, pharmaceutical companies and academia resulted in a promising synthetic artemisinin-like compound (OZ277) which is currently undergoing phase I clinical trials. In about 5 years this drug is expected to be approved and made available to the public, however, meeting current global demands for ACT depends on the immediate availability of affordable artemisinin-derived drugs. This will involve expansion of the area under cultivation of Artemisia annua and improved methods of cultivation and processing of raw material, associated with more efficient methods for extraction and purification of artemisinin from plant material. This review addresses the agricultural, environmental and genetic aspects that may be useful in the successful large-scale cultivation of A. annua and for producing the antimalarial artemisinin in areas where it is urgently needed today. It also includes geographic aspects (latitude and altitude), which will help make decisions about crop establishment in tropical countries, and includes a list of Good Agricultural and Collection Practices for A. annua.

Artemisinin (QHS) and its derivatives are new antimalarials which are effective against Plasmodium falciparum parasites resistant to chloroquine (CQ). As these drugs are introduced it is imperative that resistance is monitored. In this paper we demonstrate that the inoculum size used in in vitro testing influences the measured in vitro susceptibility to QHS and its derivative dihydroartemisinin (DHA) and to mefloquine (MEF) and CQ over the range of parasitaemias routinely used in testing with the WHO in vitro microtest. An increase in parasitaemia and/or haematocrit was accompanied by a decrease in the measured sensitivity of 2 laboratory lines. In the context of a field study testing in vitro susceptibility of parasite isolates from patients with uncomplicated malaria in Fajara, The Gambia we demonstrate that failure to control for inoculum size significantly overestimates the level of resistance to QHS and DHA as well as MEF, halofantrine (HAL) and quinine (QUIN). When controlling for the inoculum effect, cross-resistance was observed between QHS, MEF and HAL suggesting the presence of a multidrug resistance-like mechanism. These studies underline the importance of inoculum size in in vitro susceptibility testing.

A 30-h in vitro susceptibility test of Plasmodium falciparum wild isolates to artemisinin, chloroquine, sulfadoxine/pyrimethamine and mefloquine was performed in Kibaha, Tanzania. A sigmoid Emax model was fitted to all data for each isolate and drug combination. Artemisinin and mefloquine exhibited 100% growth inhibition against all isolates tested (n=69–74). The EC50 values for artemisinin and mefloquine were 44 and 146 nM respectively. Chloroquine and sulfadoxine/pyrimethamine resistance was 30% and 13% respectively. Susceptibility parameters (EC50, 90, 95 and 99 values and s) varied between compounds and isolates indicating the different sensitivity of P. falciparum isolates. No correlation between susceptibility parameters of artemisinin and the other compounds was found. The high in vitro activities of artemisinin and mefloquine indicate their potential role for the treatment of multidrug-resistant malaria in Africa.