Natural Compounds Inhibiting <em>Pseudomonas aeruginosa</em> Biofilm Formation by Targeting Quorum Sensing Circuitry

The biofilm lifestyle mode certainly represents one of the most successful behaviors to facilitate bacterial survival in diverse inhospitable environments. Conversely, the ability of bacteria to develop effective biofilms represents one of the major obstacles in the fight against bacterial infections. In Pseudomonas aeruginosa, the biofilm formation is intimately connected to the quorum sensing (QS) mechanisms, a mode of cell-to-cell communication that allows many bacteria to detect their population density in order to coordinate common actions. In this chapter, we propose an overview (i) on P. aeruginosa QS mechanisms and their implication in biofilm formation, and (ii) on natural products that are known to interfere with these QS mechanisms, subsequently disrupting biofilm formation. The concluding remarks focus on perspectives of these compounds as possible antibiotherapy adjuvants

Smallholders' knowledge about healing goat gastrointestinal parasite infections with wild plants in southern DR Congo.

peer reviewedGastrointestinal parasite (GIP) infections control has an important role to play in increasing livestock production from a limited natural resource base and to improve animal health and welfare. This study aimed to collect indigenous knowledge and identify wild plants locally used by goat smallholders of three territories of Haut-Katanga province for treating signs of gastrointestinal parasitism. Ethnoveterinary surveys were conducted by semi-structured interviews and a bibliographic screening of the biological activities relating to cited plants was carried out. Our interviews showed that ethnosemantic diagnoses of GIP diseases are based on signs. Eighty-seven informants reported that 27 plant species from 15 families, dominated by Fabaceae (29.6%) and Lamiaceae (18.5%) were commonly used in their goats treatment. Among these plants, five species with palmately compound leaves were considerably more used. From those, we noted a substitution of Vitex congolensis De Wild. and T. Durand (Lamiaceae) by Oldfieldia dactylophylla (Welw. Ex Oliv.) J. Leonard (Picrodendraceae) and of Vitex mombassae Vatke by Vitex madiensis Oliv. Subsp. Milanjiensis (Britten) F. White. Roots (46.9%), leaves (28.0%) and seeds (12.5%) were the most frequently used plant organs, and maceration is applied for most of the medicinal preparations (62.2%). Recipes were administered by oral route, for GIP 1) prevention (33.3%), by macerating the ground plant material in drinking water for 2 weeks at the start of each season (dry and rainy); and 2) treatment (66.7%). According to the literature, some of these plants have few or no studies investigating their anthelmintic activity. The cited plants are worth investigating further as they could constitute an effective alternative strategy in maintaining animal productivity. Studies on the biological activity of these plants can also provide indications of promising leads for extracts that could be developed into commercial standardized medications

HPTLC Fingerprinting and Cytotoxicity of Secondary Metabolites of Equisetum Diffusum D. Don Extracts

peer reviewedThe aerial parts of Equisetum diffusum D.Don (Equisetaceae ED), a Vietnamese folk medicine used for hypertensive, anti-inflammatory, diuretic and hemostatic properties, were collected in Northern Vietnam. The secondary metabolites of the sequential n-hexane, ethyl acetate and methanol extracts were profiled by HPTLC with chromatographic conditions and derivatization reagents characteristic for flavonoids, polyphenols and terpenoids/steroids. All these metabolite classes were present in the methanol extract whereas the ethyl acetate extract comprised some polyphenols and flavonoids; no characteristic compound class could be identified in the n-hexane extract. HPLC allowed to determine the concentration of isoquercitroside, the major flavonoid of the methanol extract (1.60 ± 0.04 mg/g dry weight; n=3)

Fluorescence capillary electrophoresis to study in vitro DNA translesion synthesis through 8-oxo-dG

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Endogenous Synthesis of Tetrahydroisoquinoline Derivatives from Dietary Factors: Neurotoxicity Assessment on a 3D Neurosphere Culture

Tetrahydroisoquinoline (THIQ) alkaloids and their derivatives have a structural similarity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a well-known neurotoxin. THIQs seem to present a broad range of actions in the brain, critically dependent on their catechol moieties and metabolism. These properties make it reasonable to assume that an acute or chronic exposure to some THIQs might lead to neurodegenerative diseases including essential tremor (ET). We developed a method to search for precursor carbonyl compounds produced during the Maillard reaction in overcooked meats to study their reactivity with endogenous amines and identify the reaction products. Then, we predicted in silico their pharmacokinetic and toxicological properties toward the central nervous system. Finally, their possible neurological effects on a novel in vitro 3D neurosphere model were assessed. The obtained data indicate that meat is an alkaloid precursor, and we identified the alkaloid 1-benzyl-1,2,3,4-tetrahydroisoquinoline-6,7-diol (1-benz-6,7-diol THIQ) as the condensation product of phenylacetaldehyde with dopamine; in silico study of 1-benz-6,7-diol-THIQ reveals modulation of dopamine receptor D1 and D2; and in vitro study of 1-benz-6,7-diol-THIQ for cytotoxicity and oxidative stress induction does not show any difference after 24 h contact for all tested concentrations. To conclude, our in vitro data do not support an eventual neurotoxic effect for 1-benz-6,7-diol-THIQ

Essential tremor: A three-dimensional neurosphere in vitro model to assess the neurotoxicity of harmane

Objectives: To use a novel in vitro model of three-dimensional (3D) neurosphere cultures to assess neurotoxic or neuroprotective effects with harmane as a model compound. Methods: A reproducible model of 3D spheroids was developed from embryonic mouse cortical neurons, using molded agarose micro-wells; this method seems particularly practical as it is customizable and widely available and does not require specific cell treatments or assay components different from 2D cultures, allowing for the easy transposition of routine protocols. To assess the neurotoxic effects of harmane, a resazurin assay was performed to measure cell viability, and a highly sensitive fluorometric method, based on the oxidation of dichlorodihydrofluorescein, was applied to measure eventually induced reactive oxygen species (ROS) after exposure to harmane at increasing concentrations of 50 100, and 250 μm. Results: Hydrogel microwells facilitated the assembly of spheroids containing neurons and glial cells into a complex 3D structure and prevented the agglomeration of spheroids. Exposure to harmane induced cytotoxicity in 3D neural spheroids, which was correlated with harmane concentrations, with a 27% reduction in viability at 250 μm. Harmane that did not induce significant levels of oxidative stress was detected for all tested concentrations. Conclusion: This 3D neurosphere model mimics a neuronal microenvironment, allowing a fine study of neurodegenerative disorders and the effects of chemicals on the brain. This model opens novel opportunities, not only from a pathogenetic point of view but also from a therapeutic perspective

Effect of chemopreventive natural compounds on DNA double-strand break repair by non-homologous end-joining

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Genotoxicity and carcinogenicity of herbal products

In 2012, the World Health Organization (WHO) recorded 14 million new cases of cancer and 8.2 million cancer-related deaths. Remarkably, the WHO estimates that 30 % of cancer mortalities are due to lifestyle choices and environmental factors that can and should be avoided. In line with these recommendations, this chapter discusses the genotoxicity and carcinogenicity of herbal products. Although often perceived as innocuous by the general public, many herbs harbor phytochemicals that are either directly reactive towards DNA or likely to disturb cellular homeostasis, cell cycle, and/or genome maintenance mechanisms; this may translate into genotoxicity, carcinogenicity, or co-carcinogenicity. Genotoxicity refers to the deleterious effect of a chemical compound or a physical event on the genetic material; such genotoxic events are considered hallmarks of cancer risk. Nevertheless, much of the damage to the genetic material can be efficiently bypassed and/or repaired by the numerous genome maintenance mechanisms of the cell and may not lead to cancer. The long-term safety evaluation is probably better investigated through carcinogenicity, which denotes the capacity of a chemical substance or a mixture of chemical substances to induce cancer or increase its incidence. The major mechanisms of carcinogenicity are discussed along with biomarkers and approved regulatory guidelines. The recent development of innovative carcinogenicity testing strategies, especially based on functional genomics, are debated and evaluated for possible application to the precocious evaluation of herbal products’ long-term safety. Finally, this chapter provides some examples of proven or suspected carcinogenic herbal products reported in the current literature.SCOPUS: ch.binfo:eu-repo/semantics/publishe

Modulation of DNA damage repair and translesion synthesis :a possible mechanism for natural products chemoprevention and indirect genotoxicity?

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