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

In Silico and In Vitro Identification of P-Glycoprotein Inhibitors from a Library of 375 Phytochemicals

Cancer therapy with clinically established anticancer drugs is frequently hampered by the development of drug resistance of tumors and severe side effects in normal organs and tissues. The demand for powerful, but less toxic, drugs is high. Phytochemicals represent an important reservoir for drug development and frequently exert less toxicity than synthetic drugs. Bioinformatics can accelerate and simplify the highly complex, time-consuming, and expensive drug development process. Here, we analyzed 375 phytochemicals using virtual screenings, molecular docking, and in silico toxicity predictions. Based on these in silico studies, six candidate compounds were further investigated in vitro. Resazurin assays were performed to determine the growth-inhibitory effects towards wild-type CCRF-CEM leukemia cells and their multidrug-resistant, P-glycoprotein (P-gp)-overexpressing subline, CEM/ADR5000. Flow cytometry was used to measure the potential to measure P-gp-mediated doxorubicin transport. Bidwillon A, neobavaisoflavone, coptisine, and z-guggulsterone all showed growth-inhibitory effects and moderate P-gp inhibition, whereas miltirone and chamazulene strongly inhibited tumor cell growth and strongly increased intracellular doxorubicin uptake. Bidwillon A and miltirone were selected for molecular docking to wildtype and mutated P-gp forms in closed and open conformations. The P-gp homology models harbored clinically relevant mutations, i.e., six single missense mutations (F336Y, A718C, Q725A, F728A, M949C, Y953C), three double mutations (Y310A-F728A; F343C-V982C; Y953A-F978A), or one quadruple mutation (Y307C-F728A-Y953A-F978A). The mutants did not show major differences in binding energies compared to wildtypes. Closed P-gp forms generally showed higher binding affinities than open ones. Closed conformations might stabilize the binding, thereby leading to higher binding affinities, while open conformations may favor the release of compounds into the extracellular space. In conclusion, this study described the capability of selected phytochemicals to overcome multidrug resistance

Activities of selected medicinal plants against multi-drug resistant Gram-negative bacteria in Cameroon

Background: Medicinal plants are used worldwide for several human ailments including bacterial infections. The present work was designed to assess the in vitro antibacterial activities of some Cameroonian medicinal plants including Entada abyssinica , Entada africana , Pentaclethra macrophylla , Allexis cauliflora , Anthocleista leibrechtsiana , Carapa procera , Carica papaya and Persea americana against Gram-negative bacteria expressing multidrug resistant (MDR) phenotypes. Methods: The microbroth dilution was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the samples against eight bacterial strains belonging to four species, Escherichia coli , Enterobacter aerogenes , Klebsiella pneumoniae and Providencia stuartii . Results: The extracts displayed selective antibacterial activities with the minimal inhibitory concentrations (MIC) values ranges of 64 to 1024 μg/mL. The most active extract was that from Pentaclethra macrophylla (TPM) that showed inhibitory activities against five of the eight (62.5%) tested bacteria. The lowest MIC value (64 μg/mL) was recorded with the crude extract of Entada africana against E. coli AG100A whilst the best MBC (256 μg/mL) value was also obtained with methanol extract of Persea americana against this bacterial strain. Conclusion: The results of the present work provide baseline information on the possible use of Pentaclethra macrophylla, Entada africana and Entada abyssinica in the treatment of selected bacterial infections

Cytotoxic flavonoids from two <i>Lonchocarpus</i> species

<p>A new isoflavone, 4′-prenyloxyvigvexin A (<b>1</b>) and a new pterocarpan, (6a<i>R</i>,11a<i>R</i>)-3,8-dimethoxybitucarpin B (<b>2</b>) were isolated from the leaves of <i>Lonchocarpus bussei</i> and the stem bark of <i>Lonchocarpus eriocalyx</i>, respectively. The extract of <i>L. bussei</i> also gave four known isoflavones, maximaisoflavone H, 7,2′-dimethoxy-3′,4′-methylenedioxyisoflavone, 6,7,3′-trimethoxy-4′,5′-methylenedioxyisoflavone, durmillone; a chalcone, 4-hydroxylonchocarpin; a geranylated phenylpropanol, colenemol; and two known pterocarpans, (6a<i>R</i>,11a<i>R</i>)-maackiain and (6a<i>R</i>,11a<i>R</i>)-edunol. (6a<i>R</i>,11a<i>R</i>)-Edunol was also isolated from the stem bark of <i>L. eriocalyx</i>. The structures of the isolated compounds were elucidated by spectroscopy. The cytotoxicity of the compounds was tested by resazurin assay using drug-sensitive and multidrug-resistant cancer cell lines. Significant antiproliferative effects with IC₅₀ values below 10 μM were observed for the isoflavones 6,7,3′-trimethoxy-4′,5′-methylenedioxyisoflavone and durmillone against leukemia CCRF-CEM cells; for the chalcone, 4-hydroxylonchocarpin and durmillone against its resistant counterpart CEM/ADR5000 cells; as well as for durmillone against the resistant breast adenocarcinoma MDA-MB231/<i>BCRP</i> cells and resistant gliobastoma U87MG<i>.</i>Δ<i>EGFR</i> cells.</p