Phenolic Compounds with Anti-virulence Properties

Natural products represent the major source of approved drugs and still play an important role in supplying chemical diversity as well as new structures for designing more efficient antimicrobials. They are also the basis for the discovery of new mechanisms of antibacterial action. In this regard, a large number of substances, mainly extracts from natural sources, have been obtained in order to identify their anti-virulence activity. In recent years, there is an increase in the study of anti-virulence natural product derivatives. Different targets have been proposed as a solution to the serious problem of bacterial antibiotic resistance. Inhibition of bacterial quorum-sensing systems has been one of the most studied; however, there are other mechanisms involved in virulence regulation, damage to the host and bacterial survival, which suggests that there are another good targets such as bacterial secretion systems, biofilm formation, two-component systems, flagellum, fimbriae, toxins and key enzymes. Within the natural products, the main anti-virulence compounds are phenolic in nature, so that the next chapter describes and analyzes the relationship between chemical structure and activity of the main phenolic compounds reported

Estudio de la actividad anti-Helicobacter pylori de la corteza de Amphipterygium adstringens /

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Antimicrobial peptides properties beyond growth inhibition and bacterial killing

Antimicrobial peptides (AMPs) are versatile molecules with broad antimicrobial activity produced by representatives of the three domains of life. Also, there are derivatives of AMPs and artificial short peptides that can inhibit microbial growth. Beyond killing microbes, AMPs at grow sub-inhibitory concentrations also exhibit anti-virulence activity against critical pathogenic bacteria, including ESKAPE pathogens. Anti-virulence therapies are an alternative to antibiotics since they do not directly affect viability and growth, and they are considered less likely to generate resistance. Bacterial biofilms significantly increase antibiotic resistance and are linked to establishing chronic infections. Various AMPs can kill biofilm cells and eradicate infections in animal models. However, some can inhibit biofilm formation and promote dispersal at sub-growth inhibitory concentrations. These examples are discussed here, along with those of peptides that inhibit the expression of traits controlled by quorum sensing, such as the production of exoproteases, phenazines, surfactants, toxins, among others. In addition, specific targets that are determinants of virulence include secretion systems (type II, III, and VI) responsible for releasing effector proteins toxic to eukaryotic cells. This review summarizes the current knowledge on the anti-virulence properties of AMPs and the future directions of their research

Pharmacological evaluation of the anxiolytic-like effects of an aqueous extract of the Raphanus sativus L. sprouts in mice

Raphanus sativus L. (Brassicaceae), commonly known as radish, is consumed worldwide as a vegetable. However, its benefits on mental health are unknown. The aim of this study was to evaluate its anxiolytic-like effects and safety using different experimental models. An aqueous extract of R. sativus sprouts (AERSS) was pharmacologically evaluated by intraperitoneal route (i.p.) at 10, 30, and 100 mg/kg and orally (p.o.) at 500 mg/kg on behavior by using open-field and plus-maze tests. In addition, its acute toxicity (LD50) was determined by the Lorke's method. Diazepam (1 mg/kg, i.p.) and buspirone (4 mg/kg, i.p.) were the reference drugs. A significant and anxiolytic-like dosage of AERSS (30 mg/kg, i.p.) resembling the effects of reference drugs was chosen to explore the involvement of GABAA/BDZs site (flumazenil, 5 mg/kg, i.p.) and serotonin 5-HT1A receptors (WAY100635, 1 mg/kg, i.p.) as a possible mechanism of action. A 500 mg/kg, p.o. dosage of AERSS produced an anxiolytic-like response equivalent to 100 mg/kg, i.p. No acute toxicity was observed since a LD50 > 2000 mg/kg, i.p. The phytochemical analysis allowed the identification and quantification of major presence of sulforaphene (2500 µM), sulforaphane (15 µM), iberin (0.75 µM), and indol-3-carbinol (0.75 µM), as major constituents. Both the GABAA/BDZs site and serotonin 5-HT1A receptors were involved in the anxiolytic-like activity of AERSS, depending on the pharmacological parameter or the experimental assay tested. Our results demonstrate that the anxiolytic activity of R. sativus sprouts involves GABAA/BDZs site and serotonin 5-HT1A receptors supporting its health benefits in the treatment of anxiety beyond the satisfaction of basic nutritional needs

Pharmacological evaluation of the anxiolytic-like effects of an aqueous extract of the Raphanus sativus L. sprouts in mice

Raphanus sativus L. (Brassicaceae), commonly known as radish, is consumed worldwide as a vegetable. However, its benefits on mental health are unknown. The aim of this study was to evaluate its anxiolytic-like effects and safety using different experimental models. An aqueous extract of R. sativus sprouts (AERSS) was pharmacologically evaluated by intraperitoneal route (i.p.) at 10, 30, and 100 mg/kg and orally (p.o.) at 500 mg/kg on behavior by using open-field and plus-maze tests. In addition, its acute toxicity (LD50) was determined by the Lorke's method. Diazepam (1 mg/kg, i.p.) and buspirone (4 mg/kg, i.p.) were the reference drugs. A significant and anxiolytic-like dosage of AERSS (30 mg/kg, i.p.) resembling the effects of reference drugs was chosen to explore the involvement of GABAA/BDZs site (flumazenil, 5 mg/kg, i.p.) and serotonin 5-HT1A receptors (WAY100635, 1 mg/kg, i.p.) as a possible mechanism of action. A 500 mg/kg, p.o. dosage of AERSS produced an anxiolytic-like response equivalent to 100 mg/kg, i.p. No acute toxicity was observed since a LD50 > 2000 mg/kg, i.p. The phytochemical analysis allowed the identification and quantification of major presence of sulforaphene (2500 µM), sulforaphane (15 µM), iberin (0.75 µM), and indol-3-carbinol (0.75 µM), as major constituents. Both the GABAA/BDZs site and serotonin 5-HT1A receptors were involved in the anxiolytic-like activity of AERSS, depending on the pharmacological parameter or the experimental assay tested. Our results demonstrate that the anxiolytic activity of R. sativus sprouts involves GABAA/BDZs site and serotonin 5-HT1A receptors supporting its health benefits in the treatment of anxiety beyond the satisfaction of basic nutritional needsThis work was partially supported by CONACyT (Grant number 256448/226454), INPRFM- NC123280.0 (M.E.G.-T.), and the Fundación Séneca – Murcia Regional Agency for Science and Technology (Comunidad Autónoma de la Región de Murcia, CARM, grant number 20855/PI/18, D.A.M.)Peer reviewe

Use of Gamma Radiation for the Genetic Improvement of Underutilized Plant Varieties

Agricultural biodiversity includes many species that have biological variants (natives, ecotypes, races, morphotypes). Their use is restricted to local areas because they do not fulfill the commercial requirements; however, it is well documented that these species are a source of metabolites, proteins, enzymes, and genes. Rescuing and harnessing them through traditional genetic breeding is time-consuming and expensive. Inducing mutagenesis may be a short-time option for its genetic improvement. A review of outstanding research was carried out, in order to become familiar with gene breeding using gamma radiation and its relevance to obtain outstanding agronomic characteristics for underutilized species. An approach was made to the global panorama of the application of gamma radiation in different conventional crop species and in vitro cultivated species, in order to obtain secondary metabolites, as well as molecular tools used for mutation screening. The varied effects of gamma radiation are essentially the result of the individual responses and phenotypic plasticity of each organism. However, even implicit chance can be reduced with specific genetic breeding, environmental adaptation, or conservation objectives

In Vitro Shoot Regeneration and Callogenesis of <i>Sechium compositum</i> (Donn. Sm.) C. Jeffrey for Plant Conservation and Secondary Metabolites Product

Sechium compositum (Cucurbitaceae) is a wild species that is distributed in the Soconusco region, Chiapas, Mexico, and the border with Guatemala. This species has an intangible biochemical value resulting from the pharmacological relevance of its secondary metabolites. However, as a consequence of the lack of knowledge about its importance, it is being displaced from its habitat at an accelerated rate, incurring the risk of genetic loss. Therefore, an in vitro culture protocol with two experimental phases was evaluated to propagate, conserve, and regenerate this species. The first phases considered the shoot propagation, adding seven concentrations (0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2 mg mL−1) of 6-benzylaminopurine (BA) and thidiazuron (TDZ) and evaluating the number of buds and shoots and the shoot height. The best multiplication response was recorded with 0.1, 0.2, 0.4, and 1.0 mg L−1 of BA and 0.1 mg L−1 of TDZ, as well as the MS base culture medium. The validation of the results of the first phase (0.1 mg L−1 of BA) was compared with the MS in an independent experiment against the control (n = 50 repetitions), obtaining a height of 52 mm, 1.36 shoots, and 9.22 buds, suggesting that this concentration is adequate for the purpose, surpassing the MS control (MS culture medium alone). Of the total volume of roots obtained with packed bud structure in the previous experimental sample, it was reduced to 14% (n = 50). The second phase consisted of inducing callus formation from stem and leaf explants through the addition of 0.5, 1.0, and 2.0 mg L−1 of TDZ and 2,4-Dichlorophenoxyacetic acid (2,4-D) to the medium. Callus induction in S. compositum was better when using the stem in a medium with 2.0 mg L−1 of 2,4-D with a value of 97.8% around the explant. The addition of 500 mg L−1 of polyvinylpyrrolidone (PVP) is also suggested to reduce oxidation. This protocol represents a significant advance in the conservation, multiplication, and callus formation of S. compositum and contributes to its rescue and revaluation in the face of the danger of extinction

Pharmacokinetics and Biological Activity of Cucurbitacins

Cucurbitacins are a class of secondary metabolites initially isolated from the Cucurbitaceae family. They are important for their analgesic, anti-inflammatory, antimicrobial, antiviral, and anticancer biological actions. This review addresses pharmacokinetic parameters recently reported, including absorption, metabolism, distribution, and elimination phases of cucurbitacins. It includes recent studies of the molecular mechanisms of the biological activity of the most studied cucurbitacins and some derivatives, especially their anticancer capacity, to propose the integration of the pharmacokinetic profiles of cucurbitacins and the possibilities of their use. The main botanical genera and species of American origin that have been studied, and others whose chemo taxonomy makes them essential sources for the extraction of these metabolites, are summarized

Anti-Pathogenic Properties of the Combination of a T3SS Inhibitory Halogenated Pyrrolidone with C-30 Furanone

Antimicrobial resistance is one of the current public health challenges to be solved. The World Health Organization (WHO) has urgently called for the development of strategies to expand the increasingly limited antimicrobial arsenal. The development of anti-virulence therapies is a viable option to counteract bacterial infections with the possibility of reducing the generation of resistance. Here we report on the chemical structures of pyrrolidones DEXT 1–4 (previously identified as furan derivatives) and their anti-virulence activity on Pseudomonas aeruginosa strains. DEXT 1–4 were shown to inhibit biofilm formation, swarming motility, and secretion of ExoU and ExoT effector proteins. Also, the anti-pathogenic property of DEXT-3 alone or in combination with furanone C-30 (quorum sensing inhibitor) or MBX-1641 (type III secretion system inhibitor) was analyzed in a model of necrosis induced by P. aeruginosa PA14. All treatments reduced necrosis; however, only the combination of C-30 50 µM with DEXT-3 100 µM showed significant inhibition of bacterial growth in the inoculation area and systemic dispersion. In conclusion, pyrrolidones DEXT 1–4 are chemical structures capable of reducing the pathogenicity of P. aeruginosa and with the potential for the development of anti-virulence combination therapies