Prevention of plant crown gall tumor development by the anti-malarial artesunate of Artemisia annua

Die antimalaria-aktive Substanz Artesunat, ein Sesquiterpen-Trioxan-Lacton-Derivat von Artemisinin, ist für seine außergewöhnlichen Hemmeffekte auf Plasmodien und Trematoden sowie die Unterdrückung der Proliferation von Tumorzellen bekannt. In der vorliegenden Untersuchung wurde die Wirkung von Artesunat auf sich schnell teilende Pflanzenzellen von Agrobacterium tumefaciens-induzierten Crown-Gall-Tumoren und Wundkalluszellen bei der Modellpflanze Ricinus communis untersucht. Niedrige, aber ständig applizierte Artesunatkonzentrationen (10 µM) reichten aus, um die Crown-Gall-Entwicklung vollständig zu unterdrücken. Innerhalb von drei Wochen erreichten die infizierten, aber mit Artesunat behandelten Pflanzen etwa die doppelte Größe der tumorisierten Pflanzen und zeigten ein reichlicheres und gesundes Blattwerk mit größeren Blättern. Artesunat verlangsamte auch die Wundkallusentwicklung und verursachte oberflächliche Nekrosen. Es verhinderte jedoch nicht die Infektion von Gurkenblättern durch echten Mehltau, Podosphaera xanthii, oder durch falschen Mehltau, Pseudoperonospora cubensis. Junge Gurkenblätter reagierten auf sehr hohe Artesunatkonzentrationen, 100 µM und höher, mit Nekrosesymptomen, jedoch nicht auf geringere Konzentrationen von 50 µM und niedriger. Diese neuartigen Befunde lassen auf einen allgemeinen und grundlegenden Wirkungsmechanismus von Artesunat bei menschlichen, tierischen und pflanzlichen Zellen schließen, nicht aber bei phytopathogenen Pilzen. Eine mögliche Anwendung von Artesunat im Biologischen Pflanzenschutz zur Verhinderung von Crown-Gall-Tumoren bei Reben (Mauke) oder wertvollen Obstbäumen wird diskutiert.The antimalarial drug artesunate, a sesquiterpene trioxane lactone derivative of artemisinin from Artemisia annua L., is known for its extraordinary inhibitory effects on plasmodia and trematodes and also for suppressing the proliferation of human tumor cells. In the present study the effect of artesunate was investigated on rapidly dividing plant cells in Agrobacterium tumefaciens-induced crown gall tumor and wound callus cells at the model plant Ricinus communis. Low concentrations of artesunate (10 µM) were sufficient to completely suppress crown gall development upon permanent application. Within three weeks the shoots of artesunate-treated plants attained about double the size of the tumor-bearing plants and showed abundant, healthy and larger leaves. Moreover, artesunate retarded wound callus development and induced superficial necroses. However, artesunate did not prevent or inhibit infections of cucumber leaves by powdery (Podosphaera xanthii) or downy mildew (Pseudoperonospora cubensis). Young cucumber leaves showed symptoms of phytotoxicity upon treatment with very high artenusate concentrations of 100 µM and higher. Lower concentrations (50 µM or less) did not cause visible necrotic lesions. These novel findings suggest a general and conserved basic mode of action of artesunate in human, animal and plant cells, except of phytopathogenic fungi. A possible application of artesunate for biological control of crown gall development in grapevine and precious fruit trees is discussed

Biopiracy <i>versus </i>one-world medicine – from colonial relicts to global collaborative concepts

Background: Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies without benefit-sharing of those, who generated the traditional knowledge, can be understood as form of neocolonialism.Hypothesis: : The One-World Medicine concept attempts to merge the best of traditional medicine from developing countries and conventional Western medicine for the sake of patients around the globe.Study design: Based on literature searches in several databases, a concept paper has been written. Legislative initiatives of the United Nations culminated in the Nagoya protocol aim to protect traditional knowledge and regulate benefit-sharing with indigenous communities. The European community adopted the Nagoya protocol, and the corresponding regulations will be implemented into national legislation among the member states. Despite pleasing progress, infrastructural problems of the health care systems in developing countries still remain. Current approaches to secure primary health care offer only fragmentary solutions at best. Conventional medicine from industrialized countries cannot be afforded by the impoverished population in the Third World. Confronted with exploding costs, even health systems in Western countries are endangered to burst. Complementary and alternative medicine (CAM) is popular among the general public in industrialized countries, although the efficacy is not sufficiently proven according to the standards of evidence-based medicine. CAM is often available without prescription as over-the-counter products with non-calculated risks concerning erroneous self-medication and safety/toxicity issues. The concept of integrative medicine attempts to combine holistic CAM approaches with evidence-based principles of conventional medicine.Conclusion: To realize the concept of One-World Medicine, a number of standards have to be set to assure safety, efficacy and applicability of traditional medicine, e.g. sustainable production and quality control of herbal products, performance of placebo-controlled, double-blind, randomized clinical trials, phytovigilance, as well as education of health professionals and patients

Biopiracy of natural products and good bioprospecting practice

Background: Biopiracy mainly focuses on the use of biological resources and/or knowledge of indigenous tribes or communities without allowing them to share the revenues generated out of economic exploitation or other non-monetary incentives associated with the resource/knowledge. Methods: Based on collaborations of scientists from five continents, we have created a communication platform to discuss not only scientific topics, but also more general issues with social relevance. This platform was termed ‘PhytCancer -Phytotherapy to Fight Cancer’ (www.phyt-cancer.uni-mainz.de). As a starting point, we have chosen the topic “biopiracy”, since we feel this is of pragmatic significance for scientists working with medicinal plants. Results: It was argued that the patenting of herbs or natural products by pharmaceutical corporations disregarded the ownership of the knowledge possessed by the indigenous communities on how these substances worked. Despite numerous court decisions in U.S.A. and Europe, several international treaties, (e.g. from United Nations, World Health Organization, World Trade Organization, the African Unity and others), sharing of a rational set of benefits amongst producers (mainly pharmaceutical companies) and indigenous communities is yet a distant reality. In this paper, we present an overview of the legal frameworks, discuss some exemplary cases of biopiracy and bioprospecting as excellent forms of utilization of natural resources. Conclusions: We suggest certain perspectives, by which we as scientists, may contribute towards prevention of biopiracy and also to foster the fair utilization of natural resources. We discuss ways, in which the interests of indigenous people especially from developing countries can be securedDeutsche Forschungsgemeinschaft/[GRK2015/1]//AlemaniaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET