Malaria is a deadly disease. Because of its reliance on tropical mosquitos for transmission, it disproportionately affects people living in the developing world: of the more than 600,000 deaths from malaria every year, over 90% occur in sub-Saharan Africa where resources are few and transportation to care facilities is difficult.1 What’s more, over the last fifty years the malaria parasite has evolved considerable resistance to tried-and-true treatments (such as chloroquine, quinine and its derivatives, along with other drugs such as sulfadoxine) in most areas where the disease is widespread.2 That’s why most physicians in the developing world are now using a class of drugs derived from a molecule calledartemisinin. This compound is very effective against the malaria parasite, and is derived fromArtemisia annua (Sweet Annie, or quing hao as it is known in the Chinese materia medica).3 It forms the cornerstone of current antimalarial therapy in the developing world. Unfortunately, isolating artemisinin from the whole plant has led to the development of drug resistance – still localized mostly to Southeast Asia, and not very widespread.4 Nevertheless, as combination artemisinin therapies are our best treatment for malaria, even these first signs of resistance are a cause for concern!
Malaria parasites first enter the liver, where they incubate for one to four weeks and then flood the bloodstream. They then enter red blood cells, where they feed on hemoglobin and clone themselves until the red blood cell bursts, spreading more parasites to infect more red blood cells. The cycles of feeding and reproduction underlie the cycles of fever that malaria patients suffer. Artemisinin and its allied molecules are able to create a burst of oxidative “free radicals” when they enter the red blood cell and interact with the iron-containing porphyrin ring (known as “heme”) at the heart of the hemoglobin protein during the parasite’s hemoglobin digestion process.5 Other mechanisms are at work as well: artemisinin seems able to bind to important gene-regulation proteins that govern cellular division, thereby affecting the parasite’s ability to clone itself. These actions damage the parasites, prevent their reproduction, and dramatically help the immune system overcome the infection. But what’s interesting is that these same mechanisms can also be of use in cases of autoimmune disease,6 other infections,7 and – of particular interest – cancer.8
It seems that the compounds inA. annua act as both cytotoxic agents – similar, in some ways, to certain types of conventional chemotherapy – and also as agents that modify the expression of genes. In the former case, the cytotoxicity of artemisinin-like compounds seems to rely on an abundance of iron to achieve the same “free radical” oxidative burst effect seen in the treatment of malaria. This also helps explain why there is little toxicity to non-malignant cells: cancer cells internalize iron at a much greater rate than healthy cells do (perhaps through increased transferrin surface receptors9), and are therefore more vulnerable to the iron-linked cytotoxicity of artemisinin.10 But in the latter case,A. annuacompounds have reduced the expression of genes involved in cellular division, in inflammation, and in the production of new blood vessels – all areas that are essential to tumor growth and survival. At the same time, these same compounds seem to increase the expression of genes related to apoptosis, or programmed cell death.
Dr. Thomas Efferth is the chair of the department of Pharmaceutical Biology at the University of Mainz, in Germany. His research over the years has taken him to many places, from the forests of Yunnan in China to his current academic role, but he has always maintained a focus on medicinal plants and their roles in cancer therapy. Familiar with concepts from Chinese medicine as well as modern biochemistry, he is able to bridge disparate areas of research, allowing him to explore unthought-of connections like the potential application ofA. annua in cancer therapy. He summarizes the last two decades of research in his most recentreview article, “From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy.”11 The research points to exciting potential for this herb in a range of cancers, from non-solid cancer cell lines like those that underlie leukemia, to breast, colon, ovarian, liver, and pancreatic cancers. Much of the activity seems related to compounds other than artemisinin (like, for example, the ubiquitous flavonoids), though that all-important molecule does seem to make this particular plant stand out. But, as we’re finding more and more, might it be possible that whole-plant preparations, with their complex synergy of chemistry that can both improve bioavailability and also enhance anti-tumor and antimalarial activity,12 are the preferable way to go?
I certainly hope this is the case. One of the big concerns around combination artemisinin / artesunate therapies is the high cost of treatment and limited distribution of the medicines, especially to low-resource sub-Saharan settings.13 Another is that, as we’ve seen, resistance to artemisinin is a growing concern. It turns out that resistance to whole-plantA. annua preparations doesn’t really occur as easily (and can even help reverse resistance in certain cases14). This most recent discovery is part of the tireless research onA. annuaconducted by Pamela Weathers of Worcester Polytechnic, here in the Northeastern US. Her lab has focused on a range of topics, including how to maximize potency and yield when growingA. annua,15 how to harvest and prepare the whole herb for use as an antimalarial,16 and more. When I had the privilege of meeting her recently, she brought a pottedArtemisia with her to a panel discussion on Lyme disease – honoring the plant first and foremost before any conversations on how to use it as medicine. This impressed me, and put Dr. Weathers firmly in the camp of researchers like Dr. Efferth and Dr. Kevin Spelman (who has advocated for whole-plant therapy in the treatment of malaria for a long time17).
In any event, whether supporting local efforts in East Africa to grow this amazing plant as a sustainable, accessible, low-cost alternative to conventional antimalarials that also helps slow an emergent resistance problem, or consideringArtemisia annua as a useful adjunct in cancer therapy, I hope that we can remember that naturally-occurring pharmacological synergies found in whole-plant preparations are often (and certainly in this case) more effective than molecular isolates. It’s time to go back to basics and consider the therapeutic potential of a simple cup of tea: it may seem simple, but it is many ways a much richer, complex, powerful and sustainable intervention.
The post Science Update: Artemisia, from Malaria to Cancer and Back to Basics appeared first on Urban Moonshine.
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