Improving the anti-diabetic and anti-hyperlipidemic activities of extra virgin olive oil by the incorporation of diallyl sulfide.

Development of novel functional foods is trending as one of the hot topics in food science and food/beverage industries. In the present study, the anti-diabetic, anti-hyperlipidemic and histo-protective effects of the extra virgin olive oil (EVOO) enriched with the organosulfur diallyl sulfide (DAS) (DAS-rich EVOO) were evaluated in alloxan-induced diabetic mice. The ingestion of EVOO (500µL daily for two weeks) attenuated alloxan-induced elevated glucose, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, lactate dehydrogenase (LDH), urea and creatinine. It also normalized the levels of triglycerides (TG), total cholesterols (TC), low-density lipoprotein-cholesterol (LDL-c) and their consequent atherogenic index of plasma (AIP) in diabetic animals. Additionally, EVOO prevented lipid peroxidation (MDA) and reduced the level of hydrogen peroxide (H2O2) in diabetic animals. Concomitantly, it enhanced the activity of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), reducing thereby tissue oxidative stress injury. The overall histologic (pancreas, liver, and kidney) alterations were also improved after EVOO ingestion. The manifest anti-diabetic, lipid-lowering and histo-protective properties of EVOO were markedly potentiated with DAS-rich EVOO suggesting possible synergistic interactions between DAS and EVOO lipophilic bioactive ingredients. Overall, EVOO and DAS-rich EVOO show promise as functional foods and/or adjuvants for the treatment of diabetes and its complications.

Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches.

To combat emerging antimicrobial-resistant microbes, there is an urgent need to develop new antimicrobials with better therapeutic profiles. For this, a series of 13 new spiropyrrolidine derivatives were designed, synthesized, characterized and evaluated for their in vitro antimicrobial, antioxidant and antidiabetic potential. Antimicrobial results revealed that the designed compounds displayed good activity against clinical isolated strains, with 5d being the most potent (MIC 3.95 mM against Staphylococcus aureus ATCC 25923) compared to tetracycline (MIC 576.01 mM). The antioxidant activity was assessed by trapping DPPH, ABTS and FRAP assays. The results suggest remarkable antioxidant potential of all synthesized compounds, particularly 5c, exhibiting the strongest activity with IC50 of 3.26 ± 0.32 mM (DPPH), 7.03 ± 0.07 mM (ABTS) and 3.69 ± 0.72 mM (FRAP). Tested for their α-amylase inhibitory effect, the examined analogues display a variable degree of α-amylase activity with IC50 ranging between 0.55 ± 0.38 mM and 2.19 ± 0.23 mM compared to acarbose (IC50 1.19 ± 0.02 mM), with the most active compounds being 5d, followed by 5c and 5j, affording IC50 of 0.55 ± 0.38 mM, 0.92 ± 0.10 mM, and 0.95 ± 0.14 mM, respectively. Preliminary structure-activity relationships revealed the importance of such substituents in enhancing the activity. Furthermore, the ADME screening test was applied to optimize the physicochemical properties and determine their drug-like characteristics. Binding interactions and stability between ligands and active residues of the investigated enzymes were confirmed through molecular docking and dynamic simulation study. These findings provided guidance for further developing leading new spiropyrrolidine scaffolds with improved dual antimicrobial and antidiabetic activities.

Chemical Composition, Antioxidant, and Antimicrobial Activities of Leaves of Ajuga Iva.

The main objective of this research was to study the biological characteristics in terms of antioxidant and antimicrobial activities of Ajuga iva and determine the best analytical and extraction methods applicable to this specie and studied compounds. A short screening of its nutritional value in terms of chemical composition is also included. A. iva leaves were analyzed for crude protein (CP), cell wall [neutral detergent fiber (NDF), acid detergent fiber (ADF), and acid detergent lignin (ADL)], minerals, fatty acids, essential oils, and phenolic compounds. Mature aerial parts of A. iva were randomly collected during the Spring season from Mograne-Zaghouan, Tunisia. Leaves of A. iva contained 13.4 ± 0.4% CP, 26.3 ± 0.35% NDF, 20.2 ± 0.42% ADF, and 5.13 ± 0.21% ADL. Mineral content (13.0 ± 0.45%) was mainly composed of potassium (4.5% g DM) and magnesium (4.25% DM). Leaves of A. iva had linolenic (26.29 ± 0.760%) and linoleic (37.66 ± 2.35%) acids as the main components of the acid profile. Thymol was found to be the most dominant (23.43%) essential oil, followed by 4-vinylguaiacol (14.27%) and linalool (13.66%). HPLC-PDA-ESI-MS/MS analysis pointed out the presence of phytoecdysteroids. Phenolic acids and flavonoids, such as glycosylated derivatives of naringenin, eriodyctiol, and apigenin, were detected in the methanol extract of A. iva leaves. Our results underline the importance of choosing proper extraction methods and solvents to extract and characterize the described compounds profile of A. iva leaves. Results also show A. iva leaves as a potential source of functional ingredients with beneficial health-promoting properties. Overall, leaves of A. iva have low biological activities (antioxidant and antimicrobial activities) with a chemical composition suitable as a feed for ruminants in rangeland pasture. It also has low-grade antibacterial or medicinal characteristics when fed to ruminants.

Biological activities and determination of the mode of action of Tunisian Globularia alypum and Cistus monspeliensis ethanolic extracts.

This study was designed to evaluate the antioxidant and antimicrobial activity of ethanolic extracts (EEs) of Cistus monspeliensis and Globularia alypum. C. monspeliensis showed the highest values of phenolic compounds. Further, it was shown that EE of C. monspeliensis displayed the highest DPPH (IC50 = 8.3 ± 1.08 mg/mL). The chemical profiles demonstrated a total of 12 and 13 phenolic compounds for C. monspeliensis and G. alypum, respectively. EEs of both plants possessed broad-spectrum antimicrobial activity when tested against Escherichia coli and Staphylococcus aureus. Treatment of studied strains with these extracts at their MICs reduced considerably the bacterial viability. The extracts did not induce total bacterial lysis, as determined by the measurement of optical density at 620 nm. Strains treated with EEs at Minimum Inhibitory Concentrations showed significant loss of tolerance to NaCl. Our results contribute to understanding the antibacterial mechanism of ethanolic extracts of the studied medicinal plants.

Impact of Zinc Excess on Germination, Growth Parameters and Oxidative Stress of Sweet Basil (Ocimum basilicum L.).

In the present study, the effects of elevated zinc concentrations on germination, physiological and biochemical parameters were investigated in basil (Ocimum basilicum L.). Results indicate that zinc excess (1-5 mM ZnSO4) did not affect germination process, but it drastically reduced vigor index and radicle elongation, and induced oxidative stress. Exposure of basil plants to 400 and 800 µM Zn decreased aerial parts and roots dry biomass, root length and leaf number. Under these conditions, the reduction of plant growth was associated with the formation of branched and abnormally shaped brown roots. Translocation factor < 1 and bioconcentration factor > 1 was observed for 100 µM Zn suggested the possible use of basil as a phytostabiliser. Excess of Zn supply (> 100 µM) decreased chlorophyll content, total phenol and total flavonoid contents. Additionally, an increased TBARS levels reflecting an oxidative burst was observed in Zn-treated plants. These findings suggest that excess Zn adversely affects plant growth, photosynthetic pigments, phenolic and flavonoid contents, and enhances oxidative stress in basil plants.

Assessing the fatty acid, essential oil composition, their radical scavenging and antibacterial activities of Schinus terebinthifolius Raddi leaves and twigs.

The fatty acid, essential oil compositions and their respective antioxidant and antibacterial activities was determined in Schinus terebinthifolius Raddi leaves and twigs. The lipid content ranged from 1.75 to 4.65% in twigs and leaves, respectively. Thirteen fatty acids were identified with α-linolenic (C18:3), palmitic (C16:0) and linoleic (C18:2) acids being the main components. The essential oils of both organs were characterized by a high amount of monoterpene hydrocarbons (68.91-74.88%) with α-phellandrene (33.06-36.18%), α-pinene (14.85-15.18%) and limonene (6.62-8.79%) being the chief components. The DPPH˙ radical scavenging assay revealed that both oils have a very weak antiradical activity. In contrast, they showed an appreciable antibacterial activity against the gram-positive Enterococcus feacium (ATCC 19434) and Streptococcus agalactiae (ATCC 13813) bacteria. These results suggest that leaves and twigs of S. terebinthifolius could be considered as an important dietary source of health promoting phytochemicals and has a good potential for use in food industry and pharmacy.

Enzyme-aided release of bioactive compounds from coriander (Coriandrum sativum L.) seeds and their residue by-products and evaluation of their antioxidant activity.

Enzyme-assisted extraction has emerged as an attractive green, cost-effective and high bioactive yielding technology by which desired bioactives with preserved or better efficacy are released. In the present study, the ability of cellulase, hemicellulase and their binary mixture (cellulase:hemicellulase; 1:1) in improving the extraction of essential oils from coriander (Coriandrum sativum L.) seeds, or the residue by-products from the distillation process containing value-added phytochemicals (fatty acids and phenolics) were evaluated. Cellulase and the binary mixture improved the extraction of essential oils by 44.2 and 40%, respectively. Application of enzymes was associated with increased amount of oxygenated terpenes in the essential oils derived from enzyme-treated samples. Linalool, camphor and geranyl acetate were the prominent compounds. From the hydrodistillation residues, a better recovery of petroselinic-rich oil with a good nutritional quality was also observed in enzyme-treated seeds. They also contained an appreciable amount of polyphenols and showed an improved antioxidant activity as revealed by the DPPH, FRAP and cellular antioxidant activity assays. The results suggested that enzyme pre-treatment allowed better recovery without alteration of the essential oil composition. The hydrodistillation residues obtained could be potentially exploited for the development of functional food ingredients and nutraceuticals.

Fatty acid composition and mechanisms of the protective effects of myrtle berry seed aqueous extract in alcohol-induced peptic ulcer in rat.

This study aimed to investigate the antiulcer and antioxidant activities of myrtle berry seed aqueous extract (MBSAE) in a peptic ulcer model induced by ethanol in male Wistar rats. MBSAE is rich in total polyphenols, total flavonoids, and unsaturated fatty acids, particularly linoleic (18:2) and oleic (18:1) acids. MBSAE also exhibited in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 172.1 µg/mL) and superoxide anion (IC50 = 200.24 µg/mL) scavenging activities. In vivo, MBSAE provided dose-dependent protection against ethanol-induced gastric and duodenal macroscopic and histological alterations. Also, it inhibited secretory profile disturbances and lipid peroxidation, and preserved normal antioxidant enzyme activities and nonenzymatic antioxidant levels. More importantly, we showed that acute alcohol intoxication increased gastric and duodenal calcium, hydrogen peroxide, and free iron levels, whereas MBSAE treatment protected against intracellular mediator deregulation. In conclusion, we suggest that MBSAE has potent protective effects against alcohol-induced peptic ulcer in rat. This protection might be related in part to its antioxidant properties as well as its opposite effects on some studied intracellular mediators.

Chemical composition, antioxidant properties and hepatoprotective effects of chamomile (Matricaria recutita L.) decoction extract against alcohol-induced oxidative stress in rat.

The present study assessed the chemical composition, antioxidant properties, and hepatoprotective effects of subacute pre-treatment with chamomile (Matricaria recutita L.) decoction extract (CDE) against ethanol (EtOH)-induced oxidative stress in rats. The colorimetric analysis demonstrated that the CDE is rich in total polyphenols, total flavonoids and condensed tannins, and exhibited an important in vitro antioxidant activity. The use of LC/MS technique allowed us to identify 10 phenolic compounds in CDE. We found that CDE pretreatment, in vivo, protected against EtOH-induced liver injury evident by plasma transaminases activity and preservation of the hepatic tissue structure. The CDE counteracted EtOH-induced liver lipoperoxidation, preserved thiol -SH groups and prevented the depletion of antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). We also showed that acute alcohol administration increased tissue and plasma hydrogen peroxide (H(2)O(2)), calcium and free iron levels. More importantly, CDE pre-treatment reversed all EtOH-induced disturbances in intracellular mediators. In conclusion, our data suggest that CDE exerted a potential hepatoprotective effect against EtOH-induced oxidative stress in rat, at least in part, by negatively regulating Fenton reaction components such as H(2)O(2) and free iron, which are known to lead to cytotoxicity mediated by intracellular calcium deregulation.

Chemodiversity of volatile oils in Thapsia garganica L. (Apiaceae).

The chemical composition of the volatile oils obtained from the roots, leaves, flowers, and stems of Thapsia garganica of Tunisian origin was investigated by GC-FID and GC/MS analyses. Sesquiterpene hydrocarbons and oxygenated monoterpenes were predominant in the oils of all plant parts. Bicyclogermacrene (21.59-35.09%) was the main component in the former compound class, whereas geranial (3.31-14.84%) and linalool (0.81-10.9%) were the most prominent ones in the latter compound class. Principal-component (PCA) and hierarchical-cluster (HCA) analyses revealed some common constituents, but also significant variability amongst the oils of the different plant parts. This organ-specific oil composition was discussed in relation to their biological and ecological functions. For the evaluation of the intraspecific chemical variability in T. garganica, the composition of the flower volatile oils from four wild populations was investigated. Bicyclogermacrene, linalool, and geranial were predominant in the oils of three populations, whereas epicubenol, ß-sesquiphellandrene, and cadina-1,4-diene were the most prominent components of the oil of one population. PCA and HCA allowed the separation of the flower oils into three distinct groups, however, no relationship was found between the volatile-oil composition and the geographical distribution and pedoclimatic conditions of the studied populations.

Morphology, physiology, and biochemistry of zinc-stressed caraway plants.

A greenhouse pot experiment was conducted to evaluate the impact of zinc supply (0, 1, and 2 mM Zn as ZnSO4) on morpho-physiological and biochemical parameters of caraway (Carum carvi L.). Exposure to different Zn concentrations for 12 weeks compromised severely all growth parameters (plant height, number of secondary branches, diameter of primary and secondary branches, fresh and dry weight of aerial parts and roots) yield and its components (number of umbels per primary branches and secondary branches; number of umbel per plant; number of seeds per plant; and the weight of 1000 seeds). These manifestations were intimately linked with excessive accumulation of Zn in roots and leaves, alteration of the content of photosynthetic pigments, and extended lipid peroxidation. A manifest increment of proline and soluble sugar content was also observed in response to Zn application. Lipid content in seeds was dropped in Zn-treated plants and the fatty acid profiles were profoundly affected as they were enriched with saturated fatty acids at the expense of unsaturated ones. While improving their oxidative stability as revealed by the reduced values calculated oxidizability and oxidative susceptibility, Zn treatment reduced the lipid nutritional quality of caraway seeds. Moreover, Zn treatment reduced the essential oil yield and its main component carvone while it enhanced the content of its precursor limonene. It also induced alteration of terpene metabolism as revealed in the redirection of the carbon flux to the shikimate/phenylpropanoid pathway resulting in the stimulation of the production of phenolic compounds and their subsequent antioxidant activities.

Chitosan-coated ultrapure silicon nanoparticles produced by laser ablation: biomedical potential in nano-oncology as a tumor-targeting nanosystem.

Ultrapure silicon nanoparticles (SiNPs) produced by femtosecond laser ablation in water have attracted great interest in the area of cancer therapy as they are efficient as photosensitizers in photodynamic therapy modality and can induce cell hyperthermia under radiofrequency radiation. Recently, we showed that these biocompatible nanoparticles were not able to reach tumors after intravenous injection in mice due to their rapid clearance from the bloodstream. In order to increase their half-life time and therefore their chances to reach and accumulate in tumors by an enhanced permeation retention (EPR) effect, a capping agent on SiNP surface acting as a colloidal stabilizer suspension is required. In this regard, this work focuses for the first time on the functionalization of SiNPs through the modification of their surface by chitosan (SiNPs-CH) in order to enhance their therapeutic properties in cancer therapy. Here, in vivo experiments were carried out during 15 days on nude mice developing a subcutaneously grafted malignant human brain tumor (glioblastoma). The characterization of SiNPs-CH showed an average hydrodynamic size of around 142 ± 65 nm as well as a relatively neutral charge (-5.2 mV) leading to a high colloidal suspension stability. The point of our work concerns the improvement of the biodistribution of SiNPs-CH with regard to tumors, the bloodstream, and organs. After the intravenous administration of 20 mg kg-1, all the studied parameters (animal behavior, organs' morphology, and histopathology) were in accord with the absence of toxicity due to SiNPs-CH, confirming their biocompatibility and even size and surface charge were modified compared to bare nanoparticles. Moreover an increased time in the bloodstream circulation of up to 7 days was observed, indicating the stealth of the nanoparticles, which could escape opsonization and premature elimination by macrophages and the reticuloendothelial system. As evidenced by silicon assessment, the interaction of the SiNPs-CH with the liver and spleen was significantly reduced compared to the bare nanoparticles. At the same time, SiNPs-CH were concentrated progressively in tumors from 12.03% after 1 day up to 39.55% after 7 days, confirming their uptake by the tumor microenvironment through the enhanced permeability retention effect. Subsequently, the silicon level declined progressively down to 33.6% after 15 days, evidencing the degradation of pH-sensitive SiNPs-CH under the acidic tumor microenvironment. Taken together, the stealthy SiNPs-CH exhibited an ideal biodistribution profile within the tumor microenvironment with a sustainable biodegradation and elimination profile, indicating their promising application in the nano-oncology field as a tumor-targeting system.

Titanate nanotubes as an efficient oral detoxifying agent against drug overdose: application in rat acetaminophen poisoning.

Voluntary drug intoxication is mainly due to drug overdose or the interaction of several drugs. Coma and its associated complications such as hypoventilation, aspiration pneumopathy, and heart rhythm disorders are the main hallmarks of drug intoxication. Conventional detoxification treatments, including gastric lavage or vomiting, administration of ipecac or activated charcoal (CH), and the use of antidotes, have proven to be inefficient and are generally associated with severe adverse effects. To overcome these limitations, titanate nanotubes (TiNTs) are proposed as an efficient emerging detoxifying agent because of their tubular shape and high adsorption capacity. In the present study, the detoxifying ability of TiNTs was evaluated on paracetamol (PR)-intoxicated rats. Results indicate that the loading ability of PR into TiNTs (70%) was significantly higher than that recorded for CH (38.6%). In simulated intestinal medium, TiNTs showed a controlled drug release of less than 10% after 72 h of incubation. In PR-intoxicated rats, TiNTs treatment resulted in a 64% decrease of PR after 4 h of poisoning versus 40% for CH. Concomitantly, TiNTs efficiently reduced PR absorption by 90% after 24 h of poisoning, attenuated the elevated levels of biochemical markers (i.e., alanine aminotransferase, aspartate aminotransferase, creatinine, and TNF-α) and mitigated oxidative stress by increasing the activity of superoxide dismutase and reducing the oxidized glutathione/total glutathione ratio, suggesting a histoprotective effect of TiNTs against paracetamol-induced toxicity in rats. In addition to their safety and high stability in the entire gastro-intestinal tract, biodistribution analysis revealed that TiNTs exhibited low intestinal absorption owing to their large cluster size of compact aggregate nanomaterials across the intestinal villi hindering the absorption of paracetamol. Collectively, these data provide a new and promising solution for in vivo detoxification. TiNTs are expected to have great potential for the treatment of voluntary and accidental intoxication in emergency care.

Physiological changes, phenolic content and antioxidant activity of Salvia officinalis L. grown under saline conditions.

BACKGROUND: Hydroponic culture was used to investigate the effect of NaCl concentrations on the growth, nutrient uptake, phenolic content and antioxidant activity of Salvia officinalis L. leaves. The antioxidant capacity of the methanolic extract of S. officinalis was evaluated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging test and ß-carotene-linoleic acid bleaching assay. Physiological and biochemical parameters of S. officinalis were assessed after 4 weeks of salt treatment with 0, 25, 50, 75 and 100 mmol L(-1) NaCl. RESULTS: Plant growth exhibited a reduction of 61% at 100 mmol L(-1) NaCl. Assessment of Na(+), K(+) and Ca(2+) and water contents of shoots and roots showed that S. officinalis is able to regulate Na(+) concentration by active compartmentation in vacuoles. Salvia officinalis phenolics were increased in response to salinity at the threshold of 75 mmol L(-1) NaCl. This herb was also found to be able to achieve important DPPH(•) quenching activity and to inhibit the ß-carotene-linoleic acid bleaching notably enhanced by salt treatment. It is interesting to highlight the correlation between the phenolic and antioxidant activity, suggesting the involvement of these compounds in this activity. CONCLUSION: Salvia officinalis treated with 75 mmol L(-1) NaCl constitutes a potential source for production of secondary metabolites useful in several applications.

Comparison of Different Extraction Methods for the Determination of Essential oils and Related Compounds from Coriander (Coriandrum sativum L.).

The volatile oil of coriander (Coriandrum sativum L.) obtained from the fruits by soxhlet-dynamic headspace (S-DHS), solvent extraction (SE), steam distillation (SD), hydrodistillation (HYD) and supercritical CO2 extraction (SC-CO2) were analyzed by GC-FID and GC-MS. The SC-CO2 offered a higher yield (4.5%, w/w) than the other used techniques. Among the identified constituents, linalool was the main compound whatever the employed extraction procedure in contrast to the remaining components which varied according to the isolation technique showing a strong effect of the method used on the composition of these minor compounds. SC-CO2 as compared to the other extraction techniques revealed its high efficiency in addition to the integrity saving of coriander fruit volatiles. Statistical analysis showed that all the detected and identified compounds were highly (P > 0.001) affected by the extraction technique used except the a-terpineol which appear stable. On the other hand, principal component analysis (PCA) revealed on the determination of one group represented by SC-CO2, S-DHS and HYD suggesting a similar essential oil composition. Obtained results show that, in Tunisian coriander essential oil, linalool was the main compound.

Protective Effect of Eucalyptus globulus Extracts Against Bleomycin-Induced Pulmonary Fibrosis in Rats.

Pulmonary fibrosis (PF) is a fibrous interstitial pneumonia that causes damage to the lung tissue and thus alters all respiratory functions. In this study, we aim to investigate the therapeutic effects of fresh leaves of Eucalyptus globulus extracts on bleomycin (BLM)-induced (PF). Twenty-four rats were divided into four groups. The control group received no treatment, the BLM group received only intratracheally BLM (2 mg/kg), the essential water of Eucalyptus globulus (EWEG) group underwent administration of BLM followed by E. globulus hydrosol (2000 mg/kg), and the essential oil of Eucalyptus globulus (EOCG) group received BLM followed by E. globulus essential oil (10 mg/kg). Gas chromatography-mass spectrometry analysis showed that the main compounds of EOEG and EWEG are eucalyptol and spathulenol. Obtained results showed that BLM-induced PF caused a large accumulation of lymphocytes and monocytes in lung bronchoalveolar lavage fluid, a high fibrosis score, and an inflammatory index coupled to an oxidative stress state assessed by an increase in lipid peroxidation and depletion of the activities of antioxidant enzymes: superoxide dismutase and catalase. Otherwise, the treatment with EWEG and EOEG reversed the deleterious effects of reactive oxygen species and the inflammation raised by BLM. E. globulus extracts could improve BLM-induced PF, thus suggesting that the latter could serve as a potential therapeutic approach for PF.

Gastroprotective and Antioxidant Properties of Trigonella foenum graecum Seeds Aqueous Extract (Fenugreek) and Omeprazole Against Ethanol-Induced Peptic Ulcer.

Trigonella foenum graecum (Fenugreek) is used in traditional phytomedicine for its anti-inflammatory, antiseptic, antidiabetic, and several other therapeutic virtues. The current study was intended to investigate the protecting effects of fenugreek seeds' aqueous extract (FSAE) using experimentally ethanol (EtOH)-induced gastric peptic ulcer in rats, as immense alcohol consumption can lead to gastric ulcer. Sixty adult male Wistar rats were divided into 6 groups of 10 each: control, EtOH (4 g/kg body weight [b.w.]), EtOH + several doses of FSAE (50, 100, and 200 mg/kg b.w.), and EtOH + Omeprazole (OM, 20 mg/kg orally [p.o.]). Animals were p.o. pretreated with FSAE for 21 days and exposed to a single oral administration of EtOH (4 g/kg b.w.) for 2 h. Gastric ulcer in rats was induced with a single dose of EtOH. Ulcer index, malondialdehyde (MDA), hydrogen peroxide (H2O2), and thiol groups (-SH) content in stomach, and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured. Our recorded results showed that EtOH induced gastric damage, evidenced by the level of oxidative stress markers such as MDA and H2O2 in rats exposed to EtOH. However, significant increases in the activities of antioxidant enzymes were recorded, such as SOD, CAT, and GPx, and a decrease in nonenzymatic antioxidants, such as (-SH). Moreover, histopathological examinations showed the presence of lesions associated with severe tissue damage in the untreated rats. Interestingly, FSAE meaningfully protects against all gastric damages caused by EtOH. We propose that FSAE exhibits protective effects in EtOH-induced peptic ulcer in rats. This protection might be related to its antioxidant and anti-inflammatory properties as well as its opposite effects on some studied intracellular mediators.

Inhibitory effect of phenolic extract from squirting cucumber (Ecballium elaterium (L.) A. Rich) seed oil on integrin-mediated cell adhesion, migration and angiogenesis.

Integrin targeted therapies by natural bioactive compounds have attracted attention in the field of oncology and cancer treatment. This study evaluates the potential of phenolic extract from the medicinal herb Ecballium elaterium L. seed oil (PEO) to inhibit the adhesion and migration of the highly invasive human fibrosarcoma cell line HT1080. At safe concentrations (up to 40 µg mL-1), results show that PEO dose-dependently inhibits adhesion and migration of HT1080 to fibronectin (IC50 = 18 µg mL-1) and fibrinogen (IC50 = 12.86 µg mL-1). These observations were associated with the reduction of cell motility and migration velocity as revealed in the Boyden chamber and random motility using two-dimensional assays, respectively. Additional experiments using integrin blocking antibodies showed that PEO at the highest safe concentration (40 µg mL-1) competitively inhibited the attachment of HT1080 cell to anti-αvß3 (>98%), anti-α5ß1 (>86%), and to a lesser extent anti-α2 (>50%) immobilized antibodies, suggesting that αvß3 and α5ß1 integrins were selectively targeted by PEO. Moreover, PEO specifically targeted these integrins in human microvascular endothelial cells (HMEC-1) and dose-dependently blocked the in vitro tubulogenesis. In the CAM model, PEO inhibited the VEGF-induced neoangiogenesis confirming its anti-angiogenic effect. Collectively, these results indicate that PEO holds promise for the development of natural integrin-targeted therapies against fibrosarcoma.

Flumequine-loaded titanate nanotubes as antibacterial agents for aquaculture farms.

Flumequine (FLUM), a quinolone-derived antibiotic is one of the most prescribed drugs in aquaculture farms. However, its intensive use becomes worrisome because of its environmental risks and the emergence of FLUM-resistant bacteria. To overcome these problems we propose in this study the encapsulation and the delivery of FLUM by titanate nanotubes (TiNTs). Optimal FLUM loading was reached by suspending the dehydrated powder nanomaterials (FLUM : TiNTs ratio = 1 : 5) in ethanol. The drug entrapment efficiency was calculated to be 80% approximately with a sustained release in PBS at 37 °C up to 5 days. Then FLUM@TiNTs was evaluated for both its in vitro drug release and antimicrobial activity against Escherichia coli (E. coli). Spectacularly high antibacterial activity compared to those of free FLUM antibiotic was obtained confirming the efficiency of TiNTs to protect FLUM from rapid degradation and transformation within bacteria improving thereby its antibacterial effect. Indeed FLUM@TiNTs was efficient to decrease gradually the bacterial viability to reach ≈5% after 5 days versus ≈75% with free FLUM. Finally, the ex vivo permeation experiments on sea bass (Dicentrachus labrax) intestine shows that TiNTs act to increase the intestinal permeation of FLUM during the experiment. Indeed the encapsulated FLUM flux increased 12 fold (1.46 µg cm2 h-1) compared to the free antibiotic (0.18 µg cm2 h-1). Thanks to its physical properties (diameter 10 nm, tubular shape…) and its high stability in the simulated intestinal medium, TiNTs are easy internalized by enterocytes, thus involving an endocytosis mechanism, and then improve intestinal permeation of FLUM. Taken together, FLUM@TiNTs hold potential as an effective approach for enhancing the antimicrobial activity of FLUM and pave the way not only for future pharmacokinetic studies in the treatment and targeting of fish infections but also for instating of novel strategies that overcome the challenges associated with the abusive use of antibiotics in fish farming.

Synthesis of Novel 1,3,4-Oxadiazole-Derived α-Aminophosphonates/α-Aminophosphonic Acids and Evaluation of Their In Vitro Antiviral Activity against the Avian Coronavirus Infectious Bronchitis Virus.

An efficient and simple approach has been developed for the synthesis of eight dialkyl/aryl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(aryl)methyl]phosphonates through the Pudovik-type reaction of dialkyl/arylphosphite with imines, obtained from 5-phenyl-1,3,4-oxadiazol-2-amine and aromatic aldehydes, under microwave irradiation. Five of them were hydrolyzed to lead to the corresponding phosphonic acids. Selected synthesized compounds were screened for their in vitro antiviral activity against the avian bronchitis virus (IBV). In the MTT cytotoxicity assay, the dose-response curve showed that all test compounds were safe in the range concentration of 540-1599 µM. The direct contact of novel synthesized compounds with IBV showed that the diethyl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethoxyphenyl)methyl]phosphonate (5f) (at 33 µM) and the [(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethylphenyl)methyl] phosphonic acid (6a) (at 1.23 µM) strongly inhibited the IBV infectivity, indicating their high virucidal activity. However, virus titers from IBV-infected Vero cells remained unchanged in response to treatment with the lowest non-cytotoxic concentrations of synthesized compounds suggesting their incapacity to inhibit the virus replication inside the host cell. Lack of antiviral activity might presumably be ascribed to their polarity that hampers their diffusion across the lipophilic cytoplasmic membrane. Therefore, the interactions of 5f and 6a were analyzed against the main coronavirus protease, papain-like protease, and nucleocapsid protein by molecular docking methods. Nevertheless, the novel 1,3,4-oxadiazole-based α-aminophosphonic acids and α-amino-phosphonates hold potential for developing new hygienic virucidal products for domestic, chemical, and medical uses.