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Breast cancer bone metastases (BCBM) result in serious skeletal morbidity. Although there have been important advances in cancer treatment methods such as surgery and chemotherapy, the complementary treatments, such as α-tocopherol acetate (ATA), still remain of key role via complementary and/or synergistic effects. The aim of this work was to study immune response in a rat model of BCBM due to Walker 256/B cells inoculation and the effect of ATA alone. Compared to the control group (CTRL), rat injected with Walker 256/B cells (5 × 10

The antifungal activity of volatile organic compounds (VOCs) from 10 Streptomyces isolates was tested using the double-dish chamber method. The VOCs-producing strain S97 exhibited the highest inhib...

Echium arenarium Guss is a Mediterranean plant traditionally used in healing skin wound and it was reported exhibiting potent antioxidant, antibacterial, and antiparasitic activities. However, antitumoral activities of this plant have not yet been explored. Here we investigated for the first time, root (EARE) and aerial part (EAAPE) extracts of E. arenarium Guss to examine cytotoxicity and apoptosis activation pathway on U266 human multiple myeloma (MM) cell line. We demonstrated that EARE and EAAPE decreased U266 cell viability in a dose dependent manner. Based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, EARE was significantly two times more efficient (IC50 value 41 μg/ml) than EAAPE (IC50 value 82 μg/ml) considering 48 h of treatment. Furthermore, after 24 h of exposure to 100 μg/ml of EARE or EAAPE, cell cycle showed remarkable increase in sub-G1 population and a decrease of U266 cells proportion in G1 phase. In addition, EARE increased cell percentage in S phase. Moreover, analysis revealed that EAAPE or EARE induced apoptosis of U266 cells after 24 h of treatment. Interestingly, depolarization of mitochondrial membrane potential and activation of caspase 3/7 were demonstrated in treated U266 cells. Phytochemical analysis of E. arenarium extracts showed that EARE exhibited the highest content of total phenolic content. Interestingly, six phenolic compounds were identified. Myricitrin was the major compound in EARE, followed by luteolin 7-O-glucoside, resorcinol, polydatin, Trans-hydroxycinnamic acid, and hyperoside. These findings proved that an intrinsic mitochondria-mediated apoptosis pathway probably mediated the apoptotic effects of E. arenarium Guss extracts on U266 cells, and this will suggest several action plans to treat MM.

Background: Nowadays, the conventional chemical compounds used in the food, pharmaceutical, and cosmetic sectors have proven to be less efficient from an economic and health point of view. Research has therefore focused on the isolation of bioactive molecules from plants or microorganisms. Objective: The study focused on the leaf’s volatile compounds determination from Myrtus communis (McEOs) and Mentha spicata (MsEOs) as well as the evaluation of phytochemical fractions and biological activities from their methanol extracts (McME and MsME). Methods: Phenolic compounds analysis revealed interesting concentrations of total phenols, flavonoids, and condensed tannins. The antibacterial activity tested on seven pathogenic bacteria has to be effectuated by the gel diffusion method. The extracts showed much better DPPH radical scavenging activity than the volatile compounds. The McEOs and MsEOs profiles analyzed by CG-MS showed a mixture of several compounds with a predominance of 1,8-Cineole (48.1%) and α-pinene (39.02%) in the case of McEOs. In the case of MsEOs, the predominant compounds were D-Carvone (78.79%), dihydrocarvone (6.16%), and 1.8 Cineole (2.33%). Results: It emerges from this study that the M. communis and M. spicata leaves, rich in phenolic and terpenic compounds, constitute a promising source of diversified biological activities and can be used in agro-food, cosmetic, and pharmaceutical sectors.

Ginger (Zingiber officinale) is considered as a nutraceutical spice, which possesses several health promotion and benefits. This study was carried out to investigate the phyto-chemical composition, the antioxidant capacities, the drug-likeness, and pharmacokinetic properties of ginger extract on kidney injury-associated osteoporosis in rats. Phenolic and flavonoid contents were assessed by standard chemical analysis methods and HPLC. In vivo protective effect was based on the use of female rats to evaluate the effect on renal injury as a result of combined osteoporosis using biochemical markers, oxidative status, and histological analyses. Results showed that ZO contained appreciable amounts of phenolics and flavonoids and it exhibited high scavenging activity. Ovariectomy-associated corticotherapy induced severe renal injury marked by altered biochemical markers (creatinine, urea, and uric acid), reduced GFR, significative oxidative damage signs, and disrupted antioxidant status in the combined osteoporotic rats. The histopathological examination revealed structural modifications of kidney tissues. However, all these changes were reversed following the use of ZO. These results confirm the renoprotective and antioxidant potential of ginger against renal injuries in osteoporotic rats.

For the first time, we reported the phytochemical composition of the volatile oil from Thymus musilii Velen (T. musilii). The antioxidant and antimicrobial activities against various food-borne and clinical pathogenic microorganisms were also tested. The thyme oil was particularly rich in thymol (67.697 ± 0.938%), and thymyl acetate (12.993 ± 0.221%). The strongest antioxidant activity of the essential oil was registered with the tests: ABTS (IC50 = 5.6 × 10−4 mg/mL) and β-carotene/linoleic acid (IC50 = 3.2 × 10−3 mg/mL). This thymol-chemotype oil was active against all microorganisms tested with an inhibition growth zone ranging from 21.33 ± 1.52 mm for Proteus mirabilis (P. mirabilis) to 37.33 ± 1.15 mm for Candida vaginalis (C. vaginalis) strain. Overall, the tested oil exhibited bactericidal and fungicidal activities and only a small quantity of the tested essential oil was found to be sufficient for inhibiting the growth of the tested microorganisms. Furthermore, molecular docking results implies that, among the bioactive compounds, β-caryophyllene interacted strongly with the active site residues of TyrRS, GLMS and Gyrase enzymes and consequently support our in vitro results with the highest inhibition potential of this essential oil against tested pathogens, especially Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Our results suggested that essential oil of T. musiliii exhibited strong biological activities with a promising source of various natural compounds.

Introduction Synthetic colourants are subject to various allergies. As a result, the use of plant-based additives has proved promising. Objective It is in this perspective that our objective was undertaken to investigate natural colourants from edible cactus. Opuntia species populations were single-sequence repeat (SSR) fingerprinted, the analysis of betalains and phenolic compounds and the evaluation of their biological potentials were also characterised. Results Photometric quantification of betalains and phenols showed an interspecific variation across Opuntia species. Opuntia ficus indica fruits showed the highest betalain [betaxanthins; 843.67 and betacyanins; 1400 mg/100 g dry weight (DW)] and polyphenol contents. Reversed-phase high-performance liquid chromatography (RP-HPLC) analysis showed that the variation of individual phenols profile was influenced by interspecific and genetic factors. Isorhamnetin-O-(di-deoxyhexosyl-hexoside) was the major compound and its content varied according to Opuntia species, while catechol was the predominant phenolic compound in O. humifusa with 1.88 μg/g DW. Concerning cactus species, Opuntia colourants exhibited a potent antiradical activity [half maximal inhibitory concentration (IC50 ) up to 1 μg/mL]. Opuntia species were effective against Gram-positive and Gram-negative bacterial strains [inhibition zone (IZ) up to 27 mm]. A high genetic diversity within Opuntia genotypes based on SSR markers was revealed. UPGMA (unweighted pair group method with arithmetic mean) dendrogram and PCoA (principal coordinate analysis) based on natural pigments and antimicrobial profiles indicated significant variation. The correlation approach proved the presence of a probably metabolic relationship between genetic markers, pigments and their biological activities. Conclusion A possible association between molecular approach and metabolic profile analysis of Opuntia allows tracing the relationship among species for its genetic conservation.

Chemical composition of Algerian Mentha rotundifolia and Myrtus communis essential oils, their insecticidal activities and their impact on some biological parameters of the Mediterranean flour moth Ephestia kuehniella were assessed. Results showed that M. rotundifolia essential oil contained piperitenone oxide (46.06%), d-limonene (9.10%), cis-piperitone oxide (6.81%), and endo-borneol (4.64%) as major compounds, while M. communis oil was rich in α-pinene (29.08%), 1,8-cineole (36.82%), α-terpineol (6.42%), geranyl acetate (4.38%), and β-linalool (4.04%). The fumigant potential and contact toxicity tests against E. kuehniella demonstrated the effectiveness of M. rotundifolia essential oil (LC50 = 0.54 μL/L air, LC50 = 0.004 μL/cm2) compared to M. communis oil (LC50 = 2.91 μL/L air, LC50 = 0.025 μL/cm2). Moreover, results revealed that all biological parameters were significantly affected (fecundity: 6 eggs/female, oviposition deterrence: 96.62%, log fertility: 0, hatching rate: 0%, copulation rate: 0% for M. rotundifolia oil against fecundity: 93 eggs/female, percentage of oviposition deterrence: 47.85%, log fertility: 6.7, hatching rate: 57%, copulation rate: 53.33% for M. communis oil). This work supports the use of botanical insecticide as active pest control agents under storage conditions.

Drought stress is one of the most prevalent environmental factors limiting faba bean (Vicia faba L.) crop productivity. β-aminobutyric acid (BABA) is a non-protein amino acid that may be involved in the regulation of plant adaptation to drought stress. The effect of exogenous BABA application on physiological, biochemical and molecular responses of faba bean plants grown under 18% PEG-induced drought stress were investigated. The results showed that the application of 1 mM of BABA improved the drought tolerance of faba bean. The application of BABA increased the leaf relative water content, leaf photosynthesis rate (A), transpiration rate (E), and stomatal conductance (gs), thereby decreased the water use efficiency. Furthermore, exogenous application of BABA decreased production of hydrogen peroxide (H2O2), malondialdehyde and electrolyte leakage levels, leading to less cell membrane damage due to oxidative stress. Regarding osmoprotectants, BABA application enhanced the accumulation of proline, and soluble sugars, which could improve the osmotic adjustment ability of faba bean under drought challenge. Interestingly, mended antioxidant enzyme activities like catalase, guaiacol peroxidase, ascorbate peroxidase and superoxide dismutase and their transcript levels may lead to counteract the damaging effects of oxidative stress and reducing the accumulation of harmful substances in BABA-treated faba bean plants. In addition, exogenous BABA significantly induced the accumulation of drought tolerance-related genes like VfMYB, VfDHN, VfLEA, VfERF, VfNCED, VfWRKY, VfHSP and VfNAC in leaves and roots, suggesting that BABA might act as a signal molecule to regulate the expression of drought tolerance-related genes.

Leishmaniasis is a parasitic disease affecting millions of people in Africa, Asia, and South America. It is considered as a major public health problem causing morbidity and mortality worldwide. Actually, the luck of vaccines and effective and less expensive antileishmanial therapy, have oriented pharmacological researches on natural antileishmanial drugs from medicinal plants. Hence, the purpose of this work is to optimize extraction parameters such as the percentage of aqueous ethanol mixture, the temperature and the time through the ultrasound bath equipment using a Box–Behnken Design (BBD) for maximal antileishmanial activity extraction from Moringa oleifera leaves. The cytotoxicity of the optimum extract was evaluated on RAW 264.7 macrophage cell line. The synergism between M. oleifera optimal extract and amphotericin B was also investigated using checkboard method. The optimum extract exhibiting the highest percent inhibition of Leishmania major promastigotes (99.15 ± 0.34%) was obtained using 16%v/v ethanol, at 60 °C for 20 min. Interestingly, this extract showed the best IC50 value of 6.87 ± 0.32 and 9.31 ± 0.72 μg/mL against promastigote and amastigote forms, respectively with no cytotoxicity on macrophage cells Raw 264.7 (SI = 17.53). Moreover, this extract showed a synergistic effect with amphotericin B (FIC = 0.375). HPLC analysis showed that at least six phenolic compounds were identified. Resorcinol, luteolin7-O-glucoside and syringic acid were the most active ones against L. major with IC50 values 3.788 ± 0.48, 10.70 ± 0.59 and 13.41 ± 0.59 μg/mL, respectively. Rutin and ferulic acid were further identified and showed moderate antileishmanial activity with IC50 values 78.51 ± 1.09 and 89.34 ± 1.22 μg/mL, respectively. Kaempferol 3-O-rutinoside was less active with IC50 value 204.4 ± 1.63 μg/mL.

In the present study we focused on the anti-asthmatic and antioxidant effects of

Fighting against the emergent coronavirus disease (COVID-19) remains a big challenge at the front of the world communities. Recent research has outlined the potential of various medicinal herbs to counteract the infection. This study aimed to evaluate the interaction of artemisinin, a sesquiterpene lactone extracted from the Artemisia genus, and its derivatives with the SARS-CoV-2 main protease. To assess their potential use against COVID-19, the interactions of the main active principle of Artemisia with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) was investigated through in silico probing. Our results showed that artemesinin and its derivatives manifested good oral absorption and bioavailability scores (0.55). They potently bound to the Mpro site of action—specifically, to its Cys145 residue. The selected compounds established two to three conventional hydrogen bonds with binding affinities ranging between −5.2 and −8.1 kcal/mol. Furthermore, artemisinin interactions with angiotensin converting enzyme 2 (ACE2) were dependent on the ACE2 allelic variants. The best score was recorded with rs961360700. A molecular dynamic simulation showed sufficient stability of the artemisinin–Mpro complex on the trajectory of 100 ns simulation frame. These binding interactions, together with drug-likeness and pharmacokinetic findings, confirmed that artemisinin might inhibit Mpro activity and explain the ethnopharmacological use of the herb and its possible antiviral activity against SARS-CoV-2 infection inducing COVID-19. Nevertheless, it interacted differently with the various ACE2 allelic variants reported to bind with the SARS-CoV-2 spike protein.

In this study, the antioxidant and anti-inflammatory effects of Zingiber officinale roscoe and Allium subhirsutum aqueous extracts were examined in a carrageenan-induced acute inflammation model. Some markers of inflammation such as hematological parameters, fibrinogen and C-reactive protein were measured. Variables reflecting oxidative stress included thiobarbituric acid reactive substances (TBARS), advanced oxidation of protein products (AOPP), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione were determined in both inflamed foci and erythrocytes. The in silico molecular docking simulation showed that the main components of Zingiber officinale roscoe and Allium subhirsutum bound to toll-like receptor 6 (TLR6) with high affinities. Moreover, histological examinations of paw edema were carried out. Both Zingiber officinale roscoe and Allium subhirsutum ameliorated the induced inflammation and oxidative stress status as outlined by anti-edematous, antioxidant and anti-inflammatory activities. Our investigation lends pharmacological support to the medical uses of these spices in the management of inflammatory disorders and oxidative damage. The results of the in silico assay satisfactory explain the in vivo effects as compared with indomethacin.

The aim of this study was to elaborate a suitable hydrogel to be used as drug carrier for antileishmanial treatment. Therefore, a PVP hydrogel was synthesized using gamma radiation technique. In the first step, PVP, agar and PEG concentrations were modified as a function of dose rate. Then, established polymers were characterized using FTIR, solid-state 13C NMR and TGA analyses. After that, rheological measurements followed to determine elastic and viscous modulus. Based on these techniques, it was found that synthesized PVP–hydrogels have the structure of a semi-interpenetrated network (SIPN). The sample containing 3% of PEG was selected to test its potential as antileishmanial drug carrier because it had the elastic modulus that fits more the application as wound dressing. As antileishmanial drug carrier, it has been shown that in the presence of hydrogel, the activity of conventional drug (Amphotericin B) on Leishmania promastigotes was markedly improved with an increase in selectivity index from 10.54 to 56.8.

Cupressus sempervirens L. is largely used in traditional medicine as an antimicrobial agent. The present study investigated the antioxidant, antibacterial and antileishmanial activities of C. sempervirens organic extracts at different phenological stages. Antioxidant activity was determined by DPPH (2,2-diphenyl-1-picrylhydrazylradical) scavenging assay, ferric reducing power and total antioxidant capacity. The antibacterial activity was evaluated against five clinical strains by disk diffusion method and minimum inhibitory concentration (MIC). The antileishmanial activity was determined against promastigote and amastigote forms of Leishmania (L.) infantum and L. major. Results of antioxidant activity showed that methanolic extract from vegetative stage had the most important activity. The ethyl acetate extract of C. sempervirens from flowering stage was the most active against Bacillus cereus (ATCC 14579) and Staphylococcus aureus (ATCC 25923) with MIC of 100 μg/mL and 50 μg/mL, respectively. Interestingly, this extract exhibited high antileishmanial activity against promastigote form of L. infantum and L. major (IC50 = 1.47 and 2.8 μg/mL, respectively) and amastigote form (IC50 = 3.61 and 5.42 μg/mL, respectively). Furthermore, ethyl acetate extract showed low cytotoxicity on macrophage cells Raw264.7 with selectivity index of 34.15 and 17.93 for L. infantum and L. major, respectively. The identification by HPLC and HPLC-MSn of active extracts of C. sempervirens revealed that major compounds of methanolic extract from vegetative stage and ethyl acetate extract from flowering stage were cupressuflavone and amentoflavone. Based on these results, C. sempervirens extracts could be used as an alternative to chemical drugs for the treatment of oxidative stress and infectious diseases.

Vitis vinifera grape is a highly cultivated crop and solid wastes generated by the wine industry are largely under exploited. Plentiful studies have intended analyzing the polyphenolic content of grape seeds but characterization of non phenolic compounds is rather scarce. The present study aimed at the selective extraction of lipid, phenolic and aqueous phases from grape seed powder (GSP) in order to establish their intimate composition, as well as their antioxidant and chelating properties underlying partly their biological effects. Major non phenolic compounds identified in the lipid phase were glyceryl-monostearate and 2-monostearin whereas fructofuranose and sucrose were the most abundant in the aqueous phase. Among the most abundant compounds detected in the various phases, the polyphenol quercetin exhibited the best affinity and free binding energy towards the active site of the calcium-dependent protease calpain. Polyphenols likely constitute the bioactive part of GSP that should be exploited as safe modulators of intracellular signaling which is likely at the basis of their health beneficial effects. Nevertheless other compounds as lipids or sugars should be valorized along with polyphenols to improve their bioavailability into highly protected organs as brain or eye.

Botrytis cinerea is one of the most important postharvest fungal pathogens causing significant losses in fresh fruits, vegetables and ornamentals. Synthetic fungicides are primarily used to control postharvest decay loss, but due to their hazardous use the recent trend is shifting toward safer and more eco-friendly alternatives. The use of antagonistic microorganisms is becoming popular throughout the world. This study investigated the antifungal, the plant growth promoting activities and the identity of volatile organic compounds (VOCs) produced by tomato-derived endophytic bacteria strains. The capacity of selected strains to prevent postharvest B. cinerea infection on tomato fruit through VOCs and soluble compounds was also studied. A collection of 50 bacterial strains was established from different organs of tomato plants sampled from six localities in Cape Bon region (Tunisia). Despite the small geographical scale, complexity and abundance of endophytic communities varied greatly according to the site of origin. Healthy tomato plants harbor diverse endophytic bacteria of Bacillus and Enterobacter genera colonizing mainly leaves with a significant enrichment with Bacillus strains. The in vitro dual culture assays showed that 36 % of the endophytic bacterial strains produce antifungal VOCs against B. cinerea. To our knowledge, this is the first report of VOCs antifungal activity produced by B. nakamurai, B. pseudomycoides, B. proteolyticus, B. thuringiensis, E. asburiae and E. cloacae against B. cinerea. About 14 % of bacterial strains produce VOCs with in vitro specific promoting effects on tomato seedling length or biomass production. The five selected antagonistic endophytic bacterial strains produced a core set of seven VOCs along with different strain-specific and known antifungal VOCs such as 3-Methylbutan-1-ol, sulfur-containing compounds, 2-Heptanone and Dodecanal. Tomato fruit bio-protection assay showed that the Enterobacter strain TR1 produces the most protective VOCs against B. cinerea infection with 3-Methylbutan-1-ol as a major volatile compound which totally suppressed B. cinerea growth and infection on tomato fruit at 0.442 mL L−1 headspace, whereas the Bacillus strains showed better protection against fungal infection when applied as vegetative cells on tomato fruit. These results support the use of the selected strains as potential biocontrol agents to reduce postharvest decay of B. cinerea, as well as 3-Methylbutan-1-ol as promising antifungal volatile to apply during postharvest commercialization of tomato fruit.

Drought and salinity are the most important environmental constraints affecting faba bean (Vicia faba L.) development and crop yield in Tunisia and other Mediterranean countries. Through using different strategies, associating in silico analysis of gene expression and qRT-PCR, this study aims at identifying key genes of faba bean molecular pathways potentially involved in salt and drought response. The impact of these stresses on several physiological and biochemical parameters were investigated in two genotypes (Bachar and Giza 3). To uncover abiotic stress-related genes and better understand the mechanisms of salt and drought stress tolerance in faba bean, a total of 25 faba bean genes were identified through in silico analysis. These genes were associated with important cellular processes such as transcription regulation, signal transport, kinases, phytohormonal signaling, and defense/stress responses. Most of the studied candidates were expressed at various levels in different organs including leaves, roots, flowers, stems, cotyledons, and seeds suggesting a potential role in the growth and development of faba bean plants. Furthermore, qRT-PCR was used to study gene expression profiles in leaves and roots of Bachar and Giza 3 plants under salt and drought stresses, and ABA treatment. The results showed that selected transcripts were differentially expressed under various treatments in both genotypes suggesting their important roles in abiotic stress tolerance responses. The osmotic-responsive genes identified in this study may be considered as potential candidates with a further application as stress selection markers for the creation of faba bean stress-tolerant varieties in various breeding programs.

This study was done to evaluate the anticancer potential of Achillea fragrantissima (Forssk.) Sch.Bip. leaves methanolic extract in detail for the first time, in addition to investigating its antimicrobial activity. The antimicrobial assay revealed that the extract exerted high activity against P. vulgaris (MIC = 156.25 µg/ml) and C. albicans (MIC = 625 µg/ml), while moderate activity was observed against other microbes. The extract was also screened against HepG2, A549, HCT116 and MCF7 cancer cells and was found to be active across all cells with highest selectivity and cytotoxic activity being observed for A549 cells (IC50 = 1.21 µg/ml). Further mechanistic studies on A549 cells showed that the extract resulted in S-phase arrest and induced apoptosis via activation of caspase-3, p53 and Bax, in addition to downregulation of Bcl-2. HR-LCMS analysis indicated the presence of 3-hydroxycoumarin, quercetin 3,3′-dimethyl ether and skullcapflavone II which might be responsible for the extract’s bioactivity.

In this study, we investigate the phytochemical profile, anticancer, and antioxidant activities of Teucrium polium methanolic extract using both in vitro and in silico approaches. The results showed the identification of 29 phytochemical compounds belonging to 13 classes of compounds and 20 tripeptides using High Resolution-Liquid Chromatography Mass Spectrometry (HR-LCMS). 13R-hydroxy-9E,11Z octadecadienoic acid, dihydrosamidin, valtratum, and cepharantine were the main compounds identified. The tested extract showed promising antioxidant activities (ABTS-IC50 = 0.042 mg/mL, 1,1-diphenyl-2-picrylhydrazyl (DPPH)-IC50 = 0.087 mg/mL, &beta, carotene-IC50 = 0.101 mg/mL and FRAP-IC50 = 0.292 mg/mL). Using both malignant Walker 256/B and MatLyLu cell lines, T. polium methanolic extract showed a dose/time-dependent antitumor activity. The molecular docking approach revealed that most of the identified molecules were specifically binding with human peroxiredoxin 5, human androgen, and human progesterone receptors with high binding affinity scores. The obtained results confirmed that T. polium is a rich source of bioactive molecules with antioxidant and antitumor potential.

The chemical profile of Teucrium polium L. (T. polium) methanolic extract was tested using liquid chromatography coupled with high resolution mass spectrometry (HR-LCMS). Disc diffusion and microdilution assays were used for the antimicrobial activities. Coxsackievirus B-3 (CVB3) and Herpes simplex virus type 2 (HSV-2) were used for the antiviral activities. Chromobacterium violaceum (ATCC 12472 and CV026) and Pseudomonas aeruginosa PAO1 were used as starter strains for the anti-quorum sensing tests. Isoprenoids are the main class of compounds identified, and 13R-hydroxy-9E,11Z-octadecadienoic acid, valtratum, rhoifolin, sericetin diacetate, and dihydrosamidin were the dominant phytoconstituents. The highest mean diameter of growth inhibition zone was recorded for Acinetobacter baumannii (19.33 &plusmn, 1.15 mm). The minimal inhibitory concentrations were ranging from 6.25 to 25 mg/mL for bacterial strains, and from 6.25 to 25 mg/mL for Candida species. The 50% cytotoxic concentration on VERO (African Green Monkey Kidney) cell lines was estimated at 209 &micro, g/mL. No antiviral activity was recorded. Additionally, T. polium extract was able to inhibit P. aeruginosa PAO1 motility in a concentration-dependent manner. However, the tested extract was able to inhibit 23.66% of the swarming and 35.25% of swimming capacities of PAO1 at 100 &micro, g/mL. These results highlighted the role of germander as a potent antimicrobial agent that can interfere with the virulence factors controlled by the quorum-sensing systems.

This study investigated Allium subhirsutum L. (AS) anticancer and antioxidant effects and inhibition of tumor angiogenesis in a murine model of skeletal metastases due to inoculation of Walker 256/B cells. Phytochemical composition of AS extract (ASE) was studied by High Resolution-Liquid Chromatography Mass Spectroscopy (HR-LCMS). Total phenolic and flavonoid contents (TPC and TFC) were determined. In vitro, the antioxidant properties were evaluated by reducing power and antiradical activity against DPPH. Cancer cells&rsquo, proliferation, apoptosis, metastatic development and angiogenesis were evaluated using Walker 256/B and MatLyLu cells. The p-coumaric acid was the major phenolic acid (1700 &micro, g/g extract). ASE showed high levels of TPC and TFC and proved potent antioxidant effects. ASE inhibited Walker 256/B and MatLyLu cells&rsquo, proliferation (Half-maximal inhibitory concentration: IC50 ≃ 150 &micro, g/mL) and induced apoptosis. In silico and in vivo assays confirmed these findings. ASE effectively acts as a chemo-preventive compound, induces apoptosis and attenuates angiogenesis and osteolytic metastases due to Walker 256/B malignant cells.

Bacterial resistance to antibiotics is a serious public health problem which is due to the immoderate and often inappropriate prescription of antibiotics. As a result, the exploitation of new bioactive molecules with limited or no side effects from natural sources and their adoption as a therapeutic alternative to synthetic molecules have become priorities. It is in this perspective that our study was undertaken with the objective was to investigate the phenological stage effect on the yield and chemical composition of essential oils extracted from Tunisian Eucalyptus (Eucalyptus globulus L.) aerial parts. The synergitic effect of this essential oil with conventional antimicrobials was also evaluated against nine pathogenic bacteria and Candida albicans ATCC 10231. The cytotoxicity of these combinations was tested on Vero cells. Gas chromatography–mass spectrometry analysis showed two different chemotypes depending on the growth stage which were characterized as 1,8-cineole (13.23%) at vegetative stage and p-cymene at full flowering (32.19%) and fructification (37.82%) stages. A predominance of monoterpene hydrocarbons (72.84%) during the fructification stage was detected with p-cymene (12.58%–37.82%) and α-pinene (10.41%–13.39%) as the determinants of this class. In relation to the phenological stage, Eucalyptus essential oil showed potent capacity to reduce stable free radical DPPH (IC50 up to 740 μg/mL) and moderate ability to reduce the concentration of iron ions (EC50 and IC50 up to 2 and 12 mg/mL, respectively). Eucalyptus globulus essential oil was active against the different bacterial strains especially during the vegetative and full flowering stages (MIC = 2 mg/mL) against Bacillus cereus ATCC 14579 and Enterococcus faecalis ATCC 29212. Candida albicans ATCC 10231 was more sensitive than bacteria during the fructification stage. The combination of Eucalyptus essential oil with ampicillin revealed a partial synergy effect toward Methicillin-resistant Staphylococcus aureus (FICI of 0.53). Nevertheless, an addition effect was recorded under the combination of amphotericin B and Eucalyptus essential oil. The cytototoxity activity showed that these associations enhanced cell viability and made Eucalyptus essential oil non toxic toward Vero cells. The results showed that the precious Eucalyptus oil in association with antimicrobial agents could be not only a promising alternative but also a potential molecular complex which is hardly recognizable by microorganisms.

The present study investigated the potential of potato peel powders, high in bioactive phenolic compounds and glycoalkaloids, to reduce weight gain in mice consuming a high-fat diet. Potato peel powders were prepared from the following fresh commercial potato varieties by hand-peeling and then freeze-drying and grinding the peels into powder: non-organic (conventionally grown) gold, red, and Russet and organically grown Russet. Mice diets (25% fat by weight) were supplemented with either 10 or 20% potato peel powders for 3 weeks. In comparison to the control diet, the isocaloric and isonitrogenous peel-containing diets induced a reduction in weight gain that ranged from 17-45% (10% peel diets) to 46-73% (20% peel diets), suggesting that differences in weight gain are associated with the potato peel source and peel concentration of the diet. Weight reductions were accompanied by reduced epididymal white adipose tissue ranging from 22 to 80% as well as changes in the microbiota analyzed using next-generation sequencing and in obesity-associated genetic biomarkers determined by the quantitative real-time polymerase chain reaction. Safety aspects and possible mechanisms of the antiobesity effects are discussed in terms of the composition of the bioactive potato peel compounds, which were determined using high-performance liquid chromatography. The results suggest that potato peels, a major peeling byproduct of potato processing used to prepare fries, chips, and potato flour, that showed exceptionally high antiobesity properties in fat mice, have the potential to serve as an antiobesity functional food.

The aim of this study was to identify peptides with antioxidant, antityrosinase and antibiofilm activities released from Vicia faba seed proteins hydrolysate. The hydrolysis pattern was performed with trypsin. Firstly, the obtained hydrolysate was fractionated by cation exchange chromatography and the fraction exhibiting the highest biological activity was then analyzed by reverse phase HPLC tandem mass spectrometry. After annotation by Peaks software (BSI, Canada) for de novo peptide sequencing, seven peptides were identified, mainly derived from storage proteins: legumin and vicilin. These peptides were further chemically synthesized to assess their antioxidant capacity, antityrosinase activity and antibiofilm ability against Pseudomonas aeruginosa PA14. Results showed that peptides P5, P6 and P7 identified as LSPGDVLVIPAGYPVAIK, VESEAGLTETWNPNHPELR and EEYDEEKEQGEEEIR respectively, displayed the highest DPPH radical scavenging activity (IC 50 = 0.25–1.9 mM). P5 was the only peptide able to chelate iron and reduce Fe 3+ to Fe 2+ . Furthermore, peptides P4 (GPLVHPQSQSQSN) and P6 were observed as potent tyrosinase inhibitors with IC 50 values of 1 and 0.14 mM respectively. P1, P5, P6 and P7 also showed interesting antibiofilm activity against Pseudomonas aeruginosa PA14 with MBIC 50 value ranged from 12 to 35 μM. Our data suggest that V. faba seed proteins hydrolysate could be potentially used as a source of natural bioactive peptides for cosmetic and pharmaceutical applications.

In our study, Allium subhirsutum L. (AS) was investigated to assess its phenolic profile and bioactive molecules including flavonoids and organosulfur compounds. The antioxidant potential of AS and wound healing activity were addressed using skin wound healing and oxidative stress and inflammation marker estimation in rat models. Phytochemical and antiradical activities of AS extract (ASE) and oil (ASO) were studied. The rats were randomly assigned to four groups: group I served as a control and was treated with simple ointment base, group II was treated with ASE ointment, group III was treated with ASO ointment and group IV (reference group, Ref) was treated with a reference drug “Cytolcentella® cream”. Phytochemical screening showed that total phenols (215 ± 3.5 mg GAE/g) and flavonoids (172.4 ± 3.1 mg QE/g) were higher in the ASO than the ASE group. The results of the antioxidant properties showed that ASO exhibited the highest DPPH free radical scavenging potential (IC50 = 0.136 ± 0.07 mg/mL), FRAP test (IC50 = 0.013 ± 0.006 mg/mL), ABTS test (IC50 = 0.52 ± 0.03 mg/mL) and total antioxidant capacity (IC50 = 0.34 ± 0.06 mg/mL). In the wound healing study, topical application of ASO performed the fastest wound-repairing process estimated by a chromatic study, percentage wound closure, fibrinogen level and oxidative damage status, as compared to ASE, the Cytolcentella reference drug and the untreated rats. The use of AS extract and oil were also associated with the attenuation of oxidative stress damage in the wound-healing treated rats. Overall, the results provided that AS, particularly ASO, has a potential medicinal value to act as effective skin wound healing agent.

Drought stress is one of the most prevalent environmental factors limiting faba bean (Vicia faba L.) crop productivity. β-aminobutyric acid (BABA) is a non-protein amino acid that may be involved in the regulation of plant adaptation to drought stress. The effect of exogenous BABA application on physiological, biochemical and molecular responses of faba bean plants grown under 18% PEG-induced drought stress were investigated. The results showed that the application of 1 mM of BABA improved the drought tolerance of faba bean. The application of BABA increased the leaf relative water content, leaf photosynthesis rate (A), transpiration rate (E), and stomatal conductance (gs), thereby decreased the water use efficiency. Furthermore, exogenous application of BABA decreased production of hydrogen peroxide (H(2)O(2)), malondialdehyde and electrolyte leakage levels, leading to less cell membrane damage due to oxidative stress. Regarding osmoprotectants, BABA application enhanced the accumulation of proline, and soluble sugars, which could improve the osmotic adjustment ability of faba bean under drought challenge. Interestingly, mended antioxidant enzyme activities like catalase, guaiacol peroxidase, ascorbate peroxidase and superoxide dismutase and their transcript levels may lead to counteract the damaging effects of oxidative stress and reducing the accumulation of harmful substances in BABA-treated faba bean plants. In addition, exogenous BABA significantly induced the accumulation of drought tolerance-related genes like VfMYB, VfDHN, VfLEA, VfERF, VfNCED, VfWRKY, VfHSP and VfNAC in leaves and roots, suggesting that BABA might act as a signal molecule to regulate the expression of drought tolerance-related genes.

The potential for apple peels to mitigate the deleterious effects of a high-fat diet in mice was investigated here. Mice were fed a high-fat diet supplemented with apple powders from three apple varieties or a commercial apple polyphenol. Polyphenols were characterized using colorimetric assays and high-performance liquid chromatography. Mice were tested for standard metabolic parameters. There was a dose response to dietary apple peels, with the higher intake leading to reduced weight gain and adipose tissue mass relative to the lower intake, but none of the treatments were statistically different from the control. The gene expression of liver enzyme stearoyl-CoA desaturase (Scd-1) was correlated with adipose weight, and liver enzyme cytochrome P51 (Cyp51) was downregulated by the apple diets. The feces from a subset of mice were analyzed for polyphenols and for bacteria taxa by next-generation sequencing. The results revealed that the makeup of the fecal microbiota was related to the metabolism of dietary polyphenols.

Thousands of polyphenolic compounds have been identified in various plants. Recently, a number of studies showed that beneficial effects of grapes are related to the presence of polyphenols, with multiple biological activities. The aim of this study was to compare the polyphenol profiles as well as biological activities of the seeds of four Tunisia cultivated grape cultivars, syrat, merlot, cabernet sauvignon and carignan. The total phenolic content of seed extracts varied between varieties and seemed to be correlated to the scavenging activity. Preliminary antibacterial results showed a good growth inhibitory activity of syrat cultivar against Staphylococcus epidermidis. To our knowledge, this is the first of such study being performed on this bacterium, known as a leading cause of Tunisian hospital-acquired infections. Gas Chromatography Mass Spectrometry analysis identified 20 polyphenol components, flavonoids being the most abundant in all extracts, followed by phenolic acids, resveratrol, tyrosol, and syringaldehyde. We also noticed a deficiency of three phenolic acid compounds (salicylic acid methyl ester, ferulic acid, Sinapic acid) as well as a flavonoid one (myricetin) in merlot cultivar, which could be responsible for its low antioxidant activity. These results will help in the selective exploitation of the seeds obtained from winemaking wastes, as well as in further pharmacological and/or in vivo investigations.

International audience; An endophytic Bacillus amyloliquefaciens strain called C5, able to produce biosurfactant lipopeptides with a broad antibacterial activity spectrum, has been isolated from the roots of olive tree. Optimization of antibacterial activity was undertaken using grape seed flour (GSF) substrate at 0.02, 0.2, and 2% (w/v) in M9 medium. Strain C5 exhibited optimal growth and antimicrobial activity (MIC value of 60 μg/ml) when incubated in the presence of 0.2% GSF while lipopeptide production culminated at 2% GSF. Thin layer chromatography analysis of lipopeptide extract revealed the presence of at least three active spots at Rf 0.35, 0.59, and 0.72 at 0.2% GSF. Data were similar to those obtained in LB-rich medium. MALDI-TOF/MS analysis of lipopeptide extract obtained from 0.2% GSF substrate revealed the presence of surfactin and bacillomycin D. These results show that GSF could be used as a low-cost culture medium supplement for optimizing the production of biosurfactants by strain C5.

Sixty two rhizospheric and endophytic bacterial strains were evaluated for their biocontrol effect on two aggressive Fusarium culmorum isolates (Fc2 and Fc3). We observed that 35 % and 23 % of the tested strains inhibited the in vitro growth of Fc2 and Fc3 respectively. The observed antagonism was due to inhibition by contact (13–19 % of the strains) or at distance (10–16 % of the strains) for both fungal isolates. Some of the antagonistic bacteria showed the ability to produce diffuse and/or volatile compounds that inhibit the growth, the sporulation and macroconidia germination of F. culmorum. None of the tested antagonistic bacteria showed chitinase activity on synthetic medium. The sequencing of the 16S rDNA genes of some antagonistic bacteria showed that they belong to the genera Bacillus, Pseudomonas and Microbacterium. The double inoculation of durum wheat seeds by the antagonistic bacterial strains (B13, B18, BSE1, BSE3 and B16E) and the two F. culmorum isolates showed that germination and seedling vigor were generally improved in vitro. The percentage of infected seeds was also reduced. In greenhouse trials, the biocontrol effectiveness of F. culmorum was dependant from the virulence of the fungal strain and the specificity of the antagonistic interaction between bacterial and fungal strains. The bacterial strains B18 and B16E reduced F. culmorum infection on durum wheat plants probably due to their antagonistic and plant growth promoting activities and they may be used in a mixture as seed biopriming inoculum for plant growth bio-promoting and Fusarium wheat diseases biocontrol.