Microbiological quality of Moroccan labeled Euphorbia resinifera honey

In the present work, microbiological profile of thirty-seven samples of labeled honey were collected in a Protected Geographical Indication “PGI” area of Tadla-Azilal region, which is an endemic zone of Euphorbia resinifera plant. A profile was assessed using conventional microbial methods, like enumeration, detection and/or germs identification, in accordance with ISO norms. This is the first study in which a honey with Moroccan “PGI” was tested, in order to assess its compliance with bacteriological recommendations. Coliforms (Total and fecal Coliforms), Salmonella spp., Shigella spp., Sporus of Bacillus cereus and Clostridium perfringens were not detected. The numbers of Standard Plate Count “SPC” were less than 102 CFU.g-1 for all samples. The molds and yeasts were found among samples and 32% and 40% of samples were positive, respectively. However, no samples showed a higher value than recommended limit [102 CFU.g-1]. We conclude that samples of labeled euphorbia honey of Tadla-Azilal analyzed present good commercial quality parameters (SPC, molds and yeasts “absence of unwanted fermentations”), a good sanitary quality (absence of coliforms and S. aureus) and are safe (Slam., Shig., Sporus of B. cereus and C. perf.). Standardization (regulation and specifications) and a rationalization of beekeeping techniques throughout Euphorbia “PGI” area studied may further sustainably improve the quality of this unique honey, and ensure it over the years

Base moléculaire des effets de l'huile d'argan sur le métabolisme mitochondrial et peroxysomal des acides gras et sur l'inflammation

L objectif des travaux de cette thèse a été d explorer les bases moléculaires de l effet de l huile d Argan (HA) sur le métabolisme lipidique au niveau mitochondriale et peroxysomale ainsi qu élucider son potentiel anti-inflammatoire. Nous avons donc montré, dans un premier temps, que les méthodes artisanales préservaient les propriétés antioxydantes d HA empêchant l oxydation de l acide férulique contrairement à l HA d origines commerciale. Ensuite, le traitement par l HA ou par les lipopolysaccharides (LPS) de fibroblastes humains, un modèle cellulaire de la pseudo-adrénoleucodystrophie néonatale (P-NALD), révèle pour l HA une prolifération des peroxysomes indépendante de l activation du récepteur nucléaire PPARa et de son coactivateur PGC-1a. Par contre, l induction de la prolifération de peroxysomes par les LPS est accompagnée d une activation de PPAR et de PGC-1 Parallèlement, une étude a été réalisée au niveau hépatique chez des souris traitées par l HA ou par les LPS. Nous avons montré pour la première fois l activité antioxydante de l huile d Argan in vivo au niveau hépatique par l induction de l activité enzymatique de la catalase peroxysomale et une activité hypolipémiante par la stimulation des activités déshydrogénases (ACADs) de la -oxydations mitochondriale des acides gars. De plus, l HA induit la transcription des gènes PPECK et G6PH de la voie de la néoglucogenèse. Nous avons montré également pour la première fois un effet préventif de l HA contre la répression des activités déshydrogénases des voies de -oxydations mitochondriale et peroxysomale, ainsi que celle la voie de la néoglucogenèse. Nos travaux démontrent que l HA possède un potentiel anti-inflammatoire, induit par le LPS, élucidé par la répression de cytokines pro-inflammatoires IL-6 et TNFa et par l induction de cytokines anti-inflammatoires IL10 et IL-4. L ensemble de nos résultats indiquerait que l huile d Argan, du fait de sa composition riche en acide gras mono et polyinsaturés et en antioxydants, a des effets hypolipémiants et anti-inflammatoires au niveau hépatique qui se traduisent par une régulation de l expression à la fois de récepteurs nucléaires et de leur gènes cibles ainsi que de certaines cytokinesThe objective of this thesis work was to explore the molecular basis of Argan Oil (AO) effects on the mitochondrial and peroxisomal lipid metabolism and to elucidate its anti-inflammatory potential. We thus showed, initially, that the artisanal method preparation preserved the antioxidant properties of AO preventing the oxidation of the ferulic acid, by contrast to AO of commercial origin. Then, the treatment by the AO or lipopolysaccharides (LPS) of human fibroblasts, the cellular model of pseudo-neonatal adrenoleukodystrophy (P-NALD), revealed for the AO that peroxisomes proliferation is independent from the activation of the nuclear receptor PPARa and the co-activator PGC-1a. On the other side, the induction of the proliferation of peroxisomes by LPS is accompanied by an activation of both PPARa and PGC-1a. At the same time, mice treatments by AO or by the LPS showed, for the first time, the hepatic antioxidant activity of AO through the induction of the activity of the peroxisomal catalase. In addition, we showed a hypolipidemic activity of AO, by the stimulation of dehydrogenase activities (ACADs) of the mitochondrial fatty acid b-oxidation. Moreover, the AO induces the transcription of genes involved in gluconeogenesis pathway (i.e. PEPCK and G6PH). We also revealed, for the first time, the preventive effect of AO against LPS repressions of mitochondrial and peroxisomal fatty acid degradation as well as on the gluconeogenic pathway. Furthermore, the AO anti-inflammatory potential has been shown, in mice treated by LPS, through the repression of the pro-inflammatory cytokines IL-6 and TNFa and by the induction of the anti-inflammatory cytokines IL10 and IL-4. All together, our results may indicate that the Argan oil, because of its composition rich in mono and polyunsaturated fatty acids and in antioxidants as well, has a hypolipidemic and an anti-inflammatory effects, which are revealed by the regulation of the expressions of nuclear receptors and their target genes including several cytokinesDIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

Relationship among antibiotic residues and antibacterial activity of the endemic spurge honey (Euphorbia Resinifera o. Berg) from morocco

Antibiotic-resistant bacteria continue to be of major health concern worldwide. In recent years, several reports and scientific articles claim the contamination of honey by antibiotics, detectable concentrations of antibiotic residues in honey are illegal. They, may cause hypersensitivity or resistance to drug therapy in humans, and are perceived by consumers as undesirable. In this sense, the purpose of this work was to examine the antibacterial activity of the Euphorbia resinifera (E. resinifera) honey against Escherichia coli and Staphylococcus aureus in vitro using the well-agar diffusion assay followed by dilution range to obtain more precise minimum inhibitory concentration values. The second aim is to evaluate the presence of antibiotics in honey using a screening test: Evidence Investigator™, an immuno-enzymatic method for detection of 27 antibiotic residues followed by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) for confirmation of suspect samples; in order to assess the relationship between the presence of antibiotic residues and the antibacterial activity of honey. In this study, a total of 37 E. resinifera honey samples were analyzed. The results show that all samples of honey inhibited the growth of bacteria at the dilutions at 50% (v/v); the highest inhibition zone (25.98 ± 0.11 mm) was recorded from sample 5 for Staphylococcus aureus and (13.84 ± 1.10 mm) in sample 17 for Escherichia coli and that 50% (v/v) dilutions showed significant antibacterial effect compared to other dilutions (6.25, 12.5, 25% (v/v)). In all samples, there were no antibiotic residues detected except for one showing the detection of Trimethoprim at 6.48 µg kg-1. Our research is one of the first studies that relate the he relationship between the presence of antibiotic residues and the antibacterial activity of Euphorbia resinifera honey and showed that the antibacterial activity of honey might be due to the high osmotic nature, a low pH, its content of phenolic compounds and hydrogen peroxide and also to its content of methylglyoxal

Cytoprotective and Antioxidants in Peroxisomal Neurodegenerative Diseases

Several of the peroxisomal neurodegenerative disorders are the consequence of a specific deficiency of an enzyme or a transporter involved in peroxisomal beta-oxidation of very long chain fatty acids [1,2]. One of the hallmarks in these peroxisomal rare neurodegenerative diseases and in other common demyelinating disorders is the accompanying oxidative damage and neuroinflammation [3]. Compelling data indicates that oxidative stress can activate microglia leading to the overproduction of pro-inflammatory molecules [4,5]. Thus, targeting oxidative stress to limit neuroinflammation may open a new pharmacological therapy window for these still incurable devastating peroxisomal diseases. Here, we present different natural (resveratrol) [6] and synthetic (organoselenides) [7] antioxidant compounds for their capacity of scavenging oxidative stress and in the perspective therapeutic use against oxidative damage in peroxisomal disorders

Deep eutectic solvent-ultrasound assisted extraction as a green approach for enhanced extraction of naringenin from Searsia tripartita and retained their bioactivities

BackgroundNaringenin (NA) is a natural flavonoid used in the formulation of a wide range of pharmaceutical, fragrance, and cosmetic products. In this research, NA was extracted from Searsia tripartita using an environmentally friendly, high efficiency extraction method: an ultrasound-assisted extraction with deep eutectic solvents (UAE-DES).MethodsSix natural deep eutectic solvent systems were tested. Choline chloride was used as the hydrogen bond acceptor (HBA), and formic acid, ethylene glycol, lactic acid, urea, glycerol, and citric acid were used as hydrogen bond donors (HBD).ResultsBased on the results of single-factor experiments, response surface methodology using a Box-Behnken design was applied to determine the optimal conditions for UAE-DES. According to the results, the optimal NA extraction parameters were as follows: DES-1 consisted of choline chloride (HBA) and formic acid (HBD) in a mole ratio of 2:1, an extraction time of 10 min, an extraction temperature of 50°C, an ultrasonic amplitude of 75 W, and a solid-liquid ratio of 1/60 g/mL. Extracted NA was shown to inhibit the activity of different enzymes in vitro, including α-amylase, acetylcholinesterase, butyrylcholinesterase, tyrosinase, elastase, collagenase, and hyaluronidase.ConclusionThus, the UAE-DES technique produced high-efficiency NA extraction while retaining bioactivity, implying broad application potential, and making it worthy of consideration as a high-throughput green extraction method

Comparative evaluation of antioxidant activity, total phenolic content, anti-inflammatory, and antibacterial potential of Euphorbia-derived functional products

This study assessed the medicinal properties of Euphorbia resinifera O. Berg (E. resinifera) and Euphorbia officinarum subsp echinus (Hook.f. and Coss.) Vindt (Euphorbia echinus, known for their pharmaceutical benefits. Extracts from their flowers, stems, propolis, and honey were examined for phenolic content, antioxidant, anti-inflammatory, and antibacterial activities. Total phenolic content (TPC), total flavonoid content (TFC), and total condensed tannin (TCC) were determined using specific methods. Antioxidant potential was assessed through various tests including DPPH, FRAP, ABTS, and Total antioxidant capacity. Anti-inflammatory effects were evaluated using phenol-induced ear edema in rats, while antibacterial activity was measured against Gram-positive (Staphylococcus aureus ATCC 6538) and Gram-negative (E. coli ATCC 10536) bacteria. Among the extracts, the aqueous propolis extract of E. resinifera demonstrated exceptional antioxidant capabilities, with low IC50 values for DPPH (0.07 ± 0.00 mg/mL) and ABTS (0.13 ± 0.00 mg/mL), as well as high TAC (176.72 ± 0.18 mg AA/mg extract) and FRAP (86.45 ± 1.45 mg AA/mg extract) values. Furthermore, the anti-inflammatory effect of E. resinifera propolis extracts surpassed that of indomethacin, yielding edema percentages of 3.92% and 11.33% for the aqueous and ethanolic extracts, respectively. Microbiological results indicated that the aqueous extract of E. resinifera flower exhibited the most potent inhibitory action against S. aureus, with an inhibition zone diameter (IZD) of 21.0 ± 0.00 mm and a minimum inhibitory concentration (MIC) of 3.125 mg/mL. Additionally, only E. resinifera honey displayed the ability to inhibit E. coli growth, with an inhibition zone diameter of 09.30 ± 0.03 mm and a MIC of 0.0433 mg/mL

Peroxisomal defects in microglial cells induce a disease-associated microglial signature

Microglial cells ensure essential roles in brain homeostasis. In pathological condition, microglia adopt a common signature, called disease-associated microglial (DAM) signature, characterized by the loss of homeostatic genes and the induction of disease-associated genes. In X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disease, microglial defect has been shown to precede myelin degradation and may actively contribute to the neurodegenerative process. We previously established BV-2 microglial cell models bearing mutations in peroxisomal genes that recapitulate some of the hallmarks of the peroxisomal β-oxidation defects such as very long-chain fatty acid (VLCFA) accumulation. In these cell lines, we used RNA-sequencing and identified large-scale reprogramming for genes involved in lipid metabolism, immune response, cell signaling, lysosome and autophagy, as well as a DAM-like signature. We highlighted cholesterol accumulation in plasma membranes and observed autophagy patterns in the cell mutants. We confirmed the upregulation or downregulation at the protein level for a few selected genes that mostly corroborated our observations and clearly demonstrated increased expression and secretion of DAM proteins in the BV-2 mutant cells. In conclusion, the peroxisomal defects in microglial cells not only impact on VLCFA metabolism but also force microglial cells to adopt a pathological phenotype likely representing a key contributor to the pathogenesis of peroxisomal disorders

Immune response of BV-2 microglial cells is impacted by peroxisomal beta-oxidation

Microglia are crucial for brain homeostasis, and dysfunction of these cells is a key driver in most neurodegenerative diseases, including peroxisomal leukodystrophies. In X-linked adrenoleukodystrophy (X-ALD), a neuroinflammatory disorder, very long-chain fatty acid (VLCFA) accumulation due to impaired degradation within peroxisomes results in microglial defects, but the underlying mechanisms remain unclear. Using CRISPR/Cas9 gene editing of key genes in peroxisomal VLCFA breakdown (Abcd1, Abcd2, and Acox1), we recently established easily accessible microglial BV-2 cell models to study the impact of dysfunctional peroxisomal β-oxidation and revealed a disease-associated microglial-like signature in these cell lines. Transcriptomic analysis suggested consequences on the immune response. To clarify how impaired lipid degradation impacts the immune function of microglia, we here used RNA-sequencing and functional assays related to the immune response to compare wild-type and mutant BV-2 cell lines under basal conditions and upon pro-inflammatory lipopolysaccharide (LPS) activation. A majority of genes encoding proinflammatory cytokines, as well as genes involved in phagocytosis, antigen presentation, and co-stimulation of T lymphocytes, were found differentially overexpressed. The transcriptomic alterations were reflected by altered phagocytic capacity, inflammasome activation, increased release of inflammatory cytokines, including TNF, and upregulated response of T lymphocytes primed by mutant BV-2 cells presenting peptides. Together, the present study shows that peroxisomal β-oxidation defects resulting in lipid alterations, including VLCFA accumulation, directly reprogram the main cellular functions of microglia. The elucidation of this link between lipid metabolism and the immune response of microglia will help to better understand the pathogenesis of peroxisomal leukodystrophies