Severity of manchineel fruit (Hippomane mancinella) poisoning: A retrospective case series of 97 patients from French Poison Control Centers

International audienceIn this retrospective series of 97 cases of manchineel fruit ingestion reported to French Poison Control Centers between 2009 and 2017, we investigated cases of poisoning due to manchineel fruit (from the Hippomane mancinella tree). This fruit is known to be responsible for oropharyngeal and gastrointestinal tract lesions and possibly hypotension and bradycardia (previously attributed to the presence of physostigmine). The most commonly observed clinical signs were oropharyngeal pain, abdominal pain, diarrhea and oropharyngeal irritation. No major gastrointestinal tract lesions were observed in the five cases in which upper gastrointestinal (GI) endoscopy was performed. One case of laryngeal edema and one case of bradycardia were observed, but analysis of the harvested fruits did not confirm the presence of physostigmine. Ingestion of manchineel fruit can cause mild abdominal pain and digestive irritation, requiring medical attention. Rarely, when several fruits have been ingested, severe oropharyngeal injury or hemodynamic disorders may require otorhinolaryngological consultation or cardiac monitoring for several hours, respectively

Clerodane furanoditerpenoids as the probable cause of toxic hepatitis induced by Tinospora crispa

International audienc

Chemical Profile, Antioxidant, Anti-Inflammatory, and Anti-Cancer Effects of Italian Salvia rosmarinus Spenn. Methanol Leaves Extracts

In this study, we evaluated and compared the chemical composition, the antioxidant, anti-inflammatory, and anti-proliferative effects of four methanol extracts (R1–R4), of Salvia rosmarinus Spenn. in two different sites of Southern Italy obtained by maceration or ultrasound-assisted extraction. Extracts of S. rosmarinus collected on the Ionian coast are indicated with the abbreviations R1 (maceration) and R2 (ultrasound-assisted extraction). Extracts of S. rosmarinus collected on the Tyrrhenian coast are indicated with the abbreviations R3 (maceration) and R4 (ultrasound-assisted extraction). The chemical composition was analyzed using High Pressure liquid chromatography–Diod-Array detection–Electrospray ionization–Quadrupole–Mass Spectroscopy (HPLC-DAD-ESI-Q-MS). The antioxidant activity was analyzed by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) 2,2-diphenyl-1-picrylhydrazyl (DPPH), β-carotene bleaching, and Ferric Reducing Antioxidant Power (FRAP) assays. Antioxidant features were also assessed in lipopolysaccharide (LPS)-stimulated RAW-264.7 murine macrophages, evaluating Reactive Oxygen Species (ROS) production; in the same experimental model, the anti-inflammatory activity of the extracts was investigated. Interestingly, all extracts displayed antioxidant and anti-inflammatory properties. They exhibited significative nitrite production inhibitory activity, whith IC50 values ranging from 3.46 to 5.53 µg/mL, without impairing cell viability. The anti-inflammatory activity was also investigated by Western Blotting and immunofluorescence assay, highlighting the R3 and R4 extracts ability to reduce NF-κB translocation, as well as to disrupt the MAPKs signaling pathway. Extracts exhibited both potential anti-proliferative activity on breast cancer cells, inducing apoptosis, without affecting non-tumorigenic cells, and the ability to inhibit MDA-MB-231 cells’ motility. Finally, the rosemary extracts treatment significantly reduced the power of conditioned media, from MCF-7 or MDA-MB-231 cells to induce nitrite production on RAW 264.7 cells, confirming their promising anti-inflammatory activity

New Insights into the Antioxidant and Anti-Inflammatory Effects of Italian <i>Salvia officinalis</i> Leaf and Flower Extracts in Lipopolysaccharide and Tumor-Mediated Inflammation Models

This work aimed to investigate and compare the in vitro antioxidant and anti-inflammatory effects of Salvia officinalis L. (sage) from Italy, with the aim of raising its current knowledge in this field. Leaves and flowers (S1–S8), harvested in two areas of Southern Italy, were extracted with methanol as a solvent by maceration or ultrasound-assisted extraction. Sage extracts, analysed by high pressure liquid chromatography-diode-array detection-electrospray ionization-quadrupole-mass spectroscopy (HPLC-DAD-ESI-Q-MS), exerted a promising antioxidant activity investigated using ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and β-carotene bleaching tests, and elicited a significant decrease in reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. The anti-inflammatory activity was analysed in the same in vitro model. All the extracts did not affect cell viability although they showed anti-inflammatory activity, as they induced a decrease in nitrite levels that was greater than 50%, when employed at 50 µg/mL. Furthermore, they elicited a decrease in nitrite levels, as well as a decline in pro-inflammatory cytokine expression. The NF-κB transcription factor proved to be involved in the mechanisms that underlie such effects. Interestingly, sage extracts were able to interfere with the inflammatory activity induced by breast cancer cell-conditioned media (nitrite levels were significantly decreased, p p S. officinalis in controlling inflammation processes related to neoplastic progression

Chemical composition, antioxidant and anti-inflammatory properties of Monarda didyma L. essential oil

In the present study, Monarda didyma L. essential oil (isolated from the flowering aerial parts of the plant) was examined to characterize its chemotype and to evaluate, in addition to the quali-quantitative chemical analysis, the associated antioxidant and anti-inflammatory activities. The plants were grown in central Italy, Urbino (PU), Marche region. Different analyses (TLC, GC-FID, GC-MS and 1H-NMR) allowed the identification of twenty compounds among which carvacrol, p-cymene and thymol were the most abundant. On this basis, the chemotype examined in the present study was indicated as Monarda didyma ct. carvacrol. The antioxidant effect was assessed by DPPH assay. Moreover, this chemotype was investigated for the anti-inflammatory effect in an in vitro setting (i.e., LPS-stimulated U937 cells). The decreased expression of pro-inflammatory cytokine IL-6 and the increased expression of miR-146a are suggestive of the involvement of the Toll-like receptor-4 signaling pathway. Although further studies are needed to better investigate the action mechanism/s underlying the results observed in the experimental setting, our findings show that M. didyma essential oil is rich in bioactive compounds (mainly aromatic monoterpenes and phenolic monoterpenes) which are most likely responsible for its beneficial effect

Pseudomonas aeruginosa virulence attenuation by Mulinium crassifolium plant from Taira Atacama's community (Calama, Chile)

International audiencePseudomonas aeruginosa is a gram-negative pathogen of great concern in immune-compromised individuals and the major cause of mortality in cystic fibrosis patients. Its pathogenicity lies in the production of myriad of virulence factors such as phenazines (pyocyanin), exoenzymes (elastase B), siderophores, exopolysaccharides and surfactants (rhamnolipids), among others. In addition, P. aeruginosa forms aggregated communities of cells encased in an extracellular matrix known as biofilms making it resistant to most of the available antibiotic agents. Following the discovery of quorum sensing (QS) system, involved in the regulation of virulence factors, resistance, and biofilm formation in P. aeruginosa, anti-virulence therapy has been adopted as a novel approach to combat the multi-drug resistance bacteria. In view of this, there has been extensive search in natural products for chemotherapeutic compounds that can override the virulence factors and their regulation by the QS communication system without affecting bacterial growth. Since plants are known repositories of secondary metabolites with chemical defense systems against environmental microbes, in this study, extract from Mulinum crasiifolium Phil. of Apiaceae family, was investigated for anti-virulence factors and anti-biofilm activities against P. aeruginosa. To perform virulence factors quantification assays, P. aeruginosa was grown in absence or presence of M. crasiifolium extract (McE) at different concentrations. The obtained results showed that McE hinder significantly pyocyanin pigment production without disturbing bacterial growth. Moreover, this anti-pyocyanin activity was found to be dose-dependent. The results demonstrated also that McE decreased elastase and rhamnolipid production. All of these effects seem to be associated to the inhibition of QS molecules production and the alteration of membrane fluidity. As a future work, we intend to evaluate the effects of the McE on in vivo models and further fractionate the McE and identify the bioactive compounds and their mechanisms of action

Pseudomonas aeruginosa virulence attenuation by Mulinium crassifolium plant from Taira Atacama's community (Calama, Chile)

International audiencePseudomonas aeruginosa is a gram-negative pathogen of great concern in immune-compromised individuals and the major cause of mortality in cystic fibrosis patients. Its pathogenicity lies in the production of myriad of virulence factors such as phenazines (pyocyanin), exoenzymes (elastase B), siderophores, exopolysaccharides and surfactants (rhamnolipids), among others. In addition, P. aeruginosa forms aggregated communities of cells encased in an extracellular matrix known as biofilms making it resistant to most of the available antibiotic agents. Following the discovery of quorum sensing (QS) system, involved in the regulation of virulence factors, resistance, and biofilm formation in P. aeruginosa, anti-virulence therapy has been adopted as a novel approach to combat the multi-drug resistance bacteria. In view of this, there has been extensive search in natural products for chemotherapeutic compounds that can override the virulence factors and their regulation by the QS communication system without affecting bacterial growth. Since plants are known repositories of secondary metabolites with chemical defense systems against environmental microbes, in this study, extract from Mulinum crasiifolium Phil. of Apiaceae family, was investigated for anti-virulence factors and anti-biofilm activities against P. aeruginosa. To perform virulence factors quantification assays, P. aeruginosa was grown in absence or presence of M. crasiifolium extract (McE) at different concentrations. The obtained results showed that McE hinder significantly pyocyanin pigment production without disturbing bacterial growth. Moreover, this anti-pyocyanin activity was found to be dose-dependent. The results demonstrated also that McE decreased elastase and rhamnolipid production. All of these effects seem to be associated to the inhibition of QS molecules production and the alteration of membrane fluidity. As a future work, we intend to evaluate the effects of the McE on in vivo models and further fractionate the McE and identify the bioactive compounds and their mechanisms of action

Pseudomonas aeruginosa virulence attenuation by Mulinium crassifolium plant from Taira Atacama's community (Calama, Chile)

International audiencePseudomonas aeruginosa is a gram-negative pathogen of great concern in immune-compromised individuals and the major cause of mortality in cystic fibrosis patients. Its pathogenicity lies in the production of myriad of virulence factors such as phenazines (pyocyanin), exoenzymes (elastase B), siderophores, exopolysaccharides and surfactants (rhamnolipids), among others. In addition, P. aeruginosa forms aggregated communities of cells encased in an extracellular matrix known as biofilms making it resistant to most of the available antibiotic agents. Following the discovery of quorum sensing (QS) system, involved in the regulation of virulence factors, resistance, and biofilm formation in P. aeruginosa, anti-virulence therapy has been adopted as a novel approach to combat the multi-drug resistance bacteria. In view of this, there has been extensive search in natural products for chemotherapeutic compounds that can override the virulence factors and their regulation by the QS communication system without affecting bacterial growth. Since plants are known repositories of secondary metabolites with chemical defense systems against environmental microbes, in this study, extract from Mulinum crasiifolium Phil. of Apiaceae family, was investigated for anti-virulence factors and anti-biofilm activities against P. aeruginosa. To perform virulence factors quantification assays, P. aeruginosa was grown in absence or presence of M. crasiifolium extract (McE) at different concentrations. The obtained results showed that McE hinder significantly pyocyanin pigment production without disturbing bacterial growth. Moreover, this anti-pyocyanin activity was found to be dose-dependent. The results demonstrated also that McE decreased elastase and rhamnolipid production. All of these effects seem to be associated to the inhibition of QS molecules production and the alteration of membrane fluidity. As a future work, we intend to evaluate the effects of the McE on in vivo models and further fractionate the McE and identify the bioactive compounds and their mechanisms of action

Natural compounds targeting pyocyanin and quorum sensing in Pseudomonas aeruginosa

International audiencePseudomonas aeruginosa is a Gram-negative bacterium representing a serious threat for individuals and public health. This opportunistic human pathogen is associated with diverse range of infections that are commonly difficult to eradicate successfully and is considered one of the important resistant bacteria to conventional antibiotic therapy at a global level. World Health Organization identified P. aeruginosa as a critical priority for which innovative new treatments are urgently needed. This study aims to attenuate bacterial virulence through interference with the expression or activity of virulence factors in P. aeruginosa. Pyocyanin is a blue redox-active toxin factor, produced by P. aeruginosa and strongly-controlled by the pqs quorum sensing (QS) system that uses alkyquinolone (AQ) derived signal molecules. A library of novel natural extracts and compounds from terrestrial plants and algae were screened on a P. aeruginosa PAO1 strain for their effects on viability, pyocyanin and QS signaling molecules production. A number of extracts and compounds tested showed significant inhibition of the targeted virulence factor. For instance, one of the selected extract (DM1) inhibited pyocyanin production in a dose-dependent manner and showed strongest activity (>80% reduction) when used at a concentration of 100 µg/ml. Accordingly, we observed a reduction on AQ production. The selected extracts and compounds will be further screened for other virulence factors production and they will be assayed alone or in combination with conventional antibiotics on a large collection of clinical strains of P. aeruginosa

Natural compounds targeting pyocyanin and quorum sensing in Pseudomonas aeruginosa

International audiencePseudomonas aeruginosa is a Gram-negative bacterium representing a serious threat for individuals and public health. This opportunistic human pathogen is associated with diverse range of infections that are commonly difficult to eradicate successfully and is considered one of the important resistant bacteria to conventional antibiotic therapy at a global level. World Health Organization identified P. aeruginosa as a critical priority for which innovative new treatments are urgently needed. This study aims to attenuate bacterial virulence through interference with the expression or activity of virulence factors in P. aeruginosa. Pyocyanin is a blue redox-active toxin factor, produced by P. aeruginosa and strongly-controlled by the pqs quorum sensing (QS) system that uses alkyquinolone (AQ) derived signal molecules. A library of novel natural extracts and compounds from terrestrial plants and algae were screened on a P. aeruginosa PAO1 strain for their effects on viability, pyocyanin and QS signaling molecules production. A number of extracts and compounds tested showed significant inhibition of the targeted virulence factor. For instance, one of the selected extract (DM1) inhibited pyocyanin production in a dose-dependent manner and showed strongest activity (>80% reduction) when used at a concentration of 100 µg/ml. Accordingly, we observed a reduction on AQ production. The selected extracts and compounds will be further screened for other virulence factors production and they will be assayed alone or in combination with conventional antibiotics on a large collection of clinical strains of P. aeruginosa