Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin

Abstract

Pharmaceutical monotherapies against human malaria have proven effective, although ephemeral, owing to the inevitable evolution of resistant parasites. Resistance to two or more drugs delivered in combination will evolve more slowly; hence combination therapies have become the preferred norm in the fight against malaria. At the forefront of these efforts has been the promotion of Artemisinin Combination Therapy, but despite these efforts, resistance to artemisinin has begun to emerge. In 2012, we demonstrated the efficacy of the whole plant (WP)-not a tea, not an infusion-as a malaria therapy and found it to be more effective than a comparable dose of pure artemisinin in a rodent malaria model. Here we show that WP overcomes existing resistance to pure artemisinin in the rodent malaria Plasmodium yoelii. Moreover, in a long-term artificial selection for resistance in Plasmodium chabaudi, we tested resilience of WP against drug resistance in comparison with pure artemisinin (AN). Stable resistance to WP was achieved three times more slowly than stable resistance to AN. WP treatment proved even more resilient than the double dose of AN. The resilience of WP may be attributable to the evolutionary refinement of the plant's secondary metabolic products into a redundant, multicomponent defense system. Efficacy and resilience of WP treatment against rodent malaria provides compelling reasons to further explore the role of nonpharmaceutical forms of AN to treat human malaria. malaria | drug resistance | artemisinin | Plasmodium | evolution

In vitro and in vivo antileishmanial activity of Artemisia annua L. leaf powder and its potential usefulness in the treatment of uncomplicated cutaneous leishmaniasis in humans

“…The content of artemisinin in the capsules containing A. annua L. leaf powder is approximately 0.1%; hence, it can be estimated that 1-3mg of artemisinin was administered daily. As the capsules only contain leaves, the possibility of the sub-therapeutic doses to generate resistance in malaria is low 29 . The advantage of A. annua L. powder, in comparison to the tea preparation, is that the powder may supply all the molecules present in the plant, particularly the polysaccharides, coumarins, saponins, phytosterols, essential oils, polyphenols, and flavonoids 30 .…”

An extract of Pueraria tuberosa tubers attenuates diabetic nephropathy by upregulating matrix metalloproteinase‐9 expression in the kidney of diabetic rats

“…44 Because the pathogenesis of DN is multi-etiological, crude extracts of plants may be more useful because they are a natural cocktail of various phytomolecules, all of which could act synergistically to achieve their therapeutic goal. [9][10][11] The present study paves a path for further studies with this plant material to develop a drug for the treatment of DN, which usually leads to ESRD, a major cause of premature death in diabetic patients. Meanwhile, the findings of the present study support the existing clinical use of P. tuberosa in Ayurveda and suggest the need for observational studies of P. tuberosa as a food supplement to manage DN.…”

“…Herbal medicines are natural cocktails of secondary metabolites and there is considerable experimental data indicating their benefits over single isolated phytochemicals. [9][10][11] In experimental animal models, DN is defined as increased urinary albumin excretion, with low creatinine clearance, a decreased glomerular filtration rate, and high serum urea and creatinine levels. Structural changes in animal models of DN include glomerulosclerosis, thickening of the basement membrane, and excessive accumulation of eosinophilic casts (EC) and extracellular matrix (ECM).…”

Analysis for Science Librarians of the 2015 Nobel Prize in Physiology or Medicine: The Life and Work of William C. Campbell, Satoshi Ōmura, and Youyou Tu

“…However, studies have shown that even these treatments lead to a high recrudescence rate and the increased potency of the plant mixture is still not enough to cure the disease. A report by Elfawal et al (2015) discusses the possibility of using the entire A. annua plant in treatment of Malaria, rather than pharmaceutically produced artemisinin. With the growing resistance to ACT, Elfawal and colleagues propose that the success of whole plant treatment in rodent models show that its use in humans should be explored.…”