Chemical composition, antifungal, antioxidant and hemolytic activities of Moroccan Thymus capitatus essential oil.

This study aimed to define the chemical composition of Moroccan Thymus capitatus essential oil, and to investigate its in vitro antioxidant and antifungal activities against human pathogenic fungi. Chemical analysis using GC-FID and GC-MS system revealed 28 constituents, representing 99% of total compounds. Oxygenated monoterpenes represented the highest proportion (79.79%), among which carvacrol (75.73%) was the predominant compound, followed by linalol (2.26%). Monoterpene hydrocarbons represented the second major fraction (16.29%): within them, the predominant constituents were γ-terpinene (5,55%), ρ-cymene (5,50%), and ß-caryophyllene (2.73%). Antioxidant activity was performed by DPPH scavenging, ß-carotene bleaching inhibition, and ferric reducing power. T. capitatus revealed pronounced DPPH radical scavenging activity (IC50=110.53µg.mL-1), strong ferric reducing ability (EC50=644.4µg.mL-1), and a remarkable degree of protection against lipid peroxidation during ß-carotene bleaching inhibition (IC50=251.76µg.mL-1). Antifungal activity was carried out against Candida, Aspergillus, and Rhizopus species by microdilution method.  T. capitatus   exhibited potent anticandidal activity (MIC=125-500µg.mL-1) and strong inhibition against filamentous fungi (MIC=250-500µg.mL-1). Its hemolytic activity against human erythrocytes had a low toxic effect at concentrations lower than 1250µg.mL-1. The useful antioxidant properties and broad antifungal effect of T. capitatus EO confirm its considerable potential for the food industry and for phytopharmaceutical production.

Saltbuch extract: a bio-solutionfor cadmium stress sorghum plants in germination and maturation.

Cadmium (Cd) is one of the dangerous factors that have negative impacts on plants and human health. Recently, many researchers have been looking for biostimulants to use as bioprotectants that can help or ameliorate plants' tolerance against abiotic stress, including Cd. To test the dangerousness of Cd accumulated in the soil, 200 µM of the latter was applied to sorghum seeds at germination and maturation stages. At the same time, Atriplex halimus water extract (0.1%, 0.25%, 0.5%) was applied to test its efficacy on Cd alleviation in sorghum plants. The obtained results showed that the tested concentrations enhanced the tolerance of sorghum to Cd by enhancing the germination indexes parameters such as germination percentage (GP), seedling vigor index (SVI), and reducing the mean germination time (MGT) of sorghum seeds grown under cadmium stress. On the other hand, the morphological parameters (height and weight) as well as the physiological parameters (chlorophyll and carotenoid) were stimulated in treated maturated sorghum plants under Cd stress. In addition, 0.5% and 0.25% of Atriplex halimus extract (AHE) stimulated the antioxidant enzymes, including superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase, and glutathione reductase. In the same time, an increase in carbon-nitrogen enzymes was recorded in the case of AHE treatment; phosphoenol pyruvate carboxylase, glutamine synthase, glutamate dehydrogenase, and amino acid transferase were all upregulated. These results suggest that using AHE as a biostimulant could be a better strategy to enhance the tolerance of sorghum plants to Cd stress.

Aqueous extract of Ceratonia siliqua L. leaves elicits antioxidant, anti-inflammatory, and AChE inhibiting effects in amyloid-ß42-induced cognitive deficit mice: Role of α7-nAChR in modulating Jak2/PI3K/Akt/GSK-3ß/ß-catenin cascade.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder attributed to several etiological factors including cholinergic dysregulation, neuroinflammation, oxidative stress, ß-amyloidogenesis, and tauopathy. This demands the search for multitarget drugs, especially of natural sources owing to their pleiotropic activities and low adverse effects. The present study was conducted to investigate the cognitive-improving potential of Ceratonia siliqua L. (Cs) extract compared with donepezil, an acetylcholinesterase inhibitor, on AD-like pathological alterations induced by single intracerebroventricular amyloid-ß42 (Aß42) injection in mice. Aß42-injected mice were treated with Cs (100 mg/kg/day, po) with or without methyllycaconitine (MLA; 1 mg/kg/day, ip), an α7-nAChR antagonist. Aß42-injected animals demonstrated an elevation of hippocampal Aß42, p-Tau, and acetylcholinesterase. They also showed a decline in phosphorylated levels of Jak2, PI3K, Akt, and GSK-3ß, leading to induction of neuroinflammation and oxidative stress. Noteworthy, Cs improved the histopathological and behavioral variables in addition to mitigating AD hallmarks. It also exerted neuroprotection by reducing NF-κBp65 and TNF-α, while elevating Nrf2 and HO-1, along with stabilizing ß-catenin under the impact of Jak2/PI3K/Akt/GSK-3ß signaling. These beneficial effects of Cs were abrogated by MLA co-administration signifying the α7-nAChR involvement in Cs-mediated effects. Therefore, Cs can ameliorate Aß42-induced neurodegeneration by modulating Jak2/PI3K/Akt/GSK-3ß/ß-catenin axis in an α7-nAChR-dependent manner.

Sage leaf rock rose water extract: a bio-solution for enhancing the growth and salt stress resistance of sorghum plants.

Sorghum bicolor, a versatile cereal grain, holds significant agronomic importance globally and plays a crucial role in addressing food insecurity. However, salinity, a major abiotic stress, poses a threat to food production by reducing soil fertility and hindering plant growth and yield. In this study, we investigated the potential of Cistus salviifolius water extract (CSE) in mitigating salt stress in sorghum plants. Salt stress severely impacted plant growth, biomass, and chlorophyll production, and reduced indole-3-acetic acid (IAA) levels, which negatively affected plant development. Salt stress also led to the buildup of reactive oxygen species (ROS), hence, resulting in oxidative harm to sorghum plants and also affecting their carbon and nitrogen metabolism. On the other hand, CSE treatments increased IAA and chlorophyll content which promoted growth under stress. Furthermore, this extract exhibited strong ROS scavenging capacity and safeguarded plants against oxidative stress by enhancing the activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, and glutathione reductase) and increasing the production of osmolytes. Additionally, CSE treatments enhanced the activities of carbon/nitrogen enzymes (phosphoenolpyruvate carboxylase, malate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase, and glutamine synthase), promoting energy synthesis and crop growth. This led to a significant increase in sorghum growth in salted soil with the highest rise recorded for 5 mg/L of CSE (an increase of 48.23% and 158.36% in length and weight compared to the salt control), which highlights this extract's potential as a biostimulant to enhance crop tolerance to salinity and contribute to sustainable agriculture.

Atriplex halimus water extract: a biochemical composition that enhanced the faba bean plants growth.

The burgeoning world population is exerting immense pressure on the agricultural sector to increase yield production, which has resulted in the widespread use of chemical products by farmers. However, these chemicals can have detrimental effects on both human health and the environment. To mitigate these risks, it is crucial to identify natural solutions that are less harmful to both humans and the environment. This study explores the impact of Atriplex halimus extract on the growth of Vicia faba L. broad vetch plants by testing three different concentrations (0.1%, 0.25%, and 0.5%) of the extract. The findings reveal that Atriplex halimus extract has a positive effect on various physiological and biochemical parameters of the plants, which ultimately leads to improved growth. Specifically, the treated plants displayed a significant (p < 0.05) increase in the content of plant metabolites and photosynthetic pigments. Furthermore, the extract enhanced the activity of enzymes that are involved in carbon-nitrogen assimilation, such as phosphoenolpyruvate carboxylase (EC 4.1.1.31), isocitrate dehydrogenase (EC 1.1.1.42), glutamine synthase (EC 6.3.1.2), glutathione-s-transferase (EC 2.5.1.18), and glutathione reductase (EC 1.8.1.7). The most significant improvement was observed in plants treated with 0.25% of Atriplex halimus extract. Therefore, it can be inferred that the application of Atriplex halimus extract has the potential to be an effective biostimulant for improving the growth and yield of faba bean plants.

Determination of the polyphenolic content of Ammodaucus leucotrichus Cosson and Durieu by liquid chromatography coupled with mass spectrometry and evaluation of the antioxidant and antiglycation properties.

Ammodaucus leucotrichus Cosson and Durieu, known as Sahara cumin, is a plant belonging to the Apiaceae family with a very strong smell of anise growing in the maritime sands in the countries of North Africa. The present work aims to study the polyphenolic profile of its seeds hydroalcoholic extract along with the determination of the antioxidant and antiglycation properties. The phytochemical screening revealed the presence of 16 compounds, out of which 15 have been detected in this extract for the first time. Luteolin-glucoside turned out to be the most abundant one (281.32 ± 0.34 mg/kg), followed by apigenin-hexoside (235.06 ± 0.29 mg/kg) and luteolin (202.41 ± 0.40 mg/kg). In terms of antioxidant activity, a half-maximal inhibitory concentration value as high as 0.39 ± 0.003 mg AAE/ml (w/v) was attained. Further, the antiglycation activity was determined to yield interesting results: at a concentration of 1.5 mg/ml, the extract showed an antiglycation activity (%I) of 61.86 compared to metformin as a positive control (%I = 84.01); on the other hand, increasing the concentration to 10 mg/ml, the inhibition activity switched to advanced glycation end products formation activation (%I = 41.71).

Dittrichia viscosa L. Leaves: A Valuable Source of Bioactive Compounds with Multiple Pharmacological Effects.

This work focused on the leaves of Dittrichia viscosa, a plant used in Mediterranean folk medicine. Compared to water extract, the methanolic extract had higher antioxidant effects. Moreover, this extract showed potent in vitro inhibitory activity against α-amylase and α-glucosidase and showed an interesting antiglycation effect. Additionally, the evaluation of the cytotoxic activity of the methanolic extract against two human breast cancer cell lines, MCF-7 and MDA-MB-468, was very promising, with no cytotoxicity towards normal cells (peripheral blood mononuclear cells (PBMCs). The antibacterial effect was also assessed and showed potent inhibitory activity against Proteus mirabilis and Bacillus subtilis. On the other hand, Dittrichia viscosa leaves were rich in macro-elements containing appropriate micro-elements and high levels of phenolics and flavonoids such as caffeic acid derivatives. Taken together, the results obtained in this study indicate that Dittrichia viscosa could constitute a valuable source of bioactive molecules and could be used either on the preventive side or for therapeutic applications without toxicity.

Insight into Cistus salviifolius extract for potential biostimulant effects in modulating cadmium-induced stress in sorghum plant.

The main aim of the current study was to investigate the role of Cistus salviifolius leaves extract (CSE) in alleviating the toxic effect of cadmium (Cd) in sorghum (Sorghum bicolor) plants. The plants exposed to Cd (200 µM) exhibited limited growth, reduced biomass, and chlorophyll content compared to unstressed ones. Nevertheless, supplementation of CSE restored the negative effect of Cd and increased biomass and pigment content. CSE also increased the activities of antioxidant enzymes such as superoxide dismutase (SOD), isocitrate dehydrogenase (ICDH), glutathione peroxidase (GPx), glutathione reductase (GR), and Glutathione-S-Transferase (GST). Furthermore, supplementation of CSE decreased lipid peroxidation and further increased the content of soluble sugar and amino acid. We also found that CSE has a promising effect in modulating the perturbations of carbon and nitrogen metabolism in sorghum plants under Cd stress by examining several carbon-nitrogen enzyme activities: phosphoenolpyruvate carboxylase (PEPC), malate dehydrogenase (NAD-MDH), glutamine synthase (GS), glutamate dehydrogenase (GDH), and aspartate aminotransferase (AAT). Overall, our results confirm that the application of CSE can be a promising mechanism to overcome the negative effects of Cd stress in sorghum plants.

Promising effects of Rosa damascena petal extracts as antioxidant and antibacterial agents.

In the present work, the antioxidant properties of methanolic (MeOH), ethyl acetate (EtOAc) and chloroformic (CHCl3) fractions of Rosa damascena petals were evaluated. Antioxidant capacity was assessed by free radical scavenging assays (DPPH•) and ferrous ions (Fe2+) chelating activity. Antibacterial activity was evaluated using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and IC50. Qualitative analysis of chemical composition was carried out by HPLC and showed variability in the chemical constituents with a richness in flavonones and phenolic acids. Acute toxicity study and hemolysis test were also assessed. The MeOH and EtOAc fractions are of real and potential interest by their antioxidant activities. Furthermore, the microbiological study of the fractions showed a high activity of the EtOAc fraction which possesses bactericidal properties, followed by a moderate activity of the methanolic MeOH. The most sensitive strains were S. aureus and B. cereus while the most resistant were P. aeruginosa and E. coli (R). On the other side, no cytotoxicity was observed towards erythrocytes isolated from human blood and on a warm-blooded animal model. Therefore, the R. damascena petals constitute a promising source of molecules for clinical use without cytoxicity.

Phytochemical Characterization, Antioxidant and In Vitro Cytotoxic Activity Evaluation of Juniperus oxycedrus Subsp. oxycedrus Needles and Berries.

In order to evaluate the antioxidant properties of aqueous and methanol extracts of needles and berries of Juniperus oxycedrus subsp. oxycedrus (Joo) species, various antioxidant capacity assessment tests (free radical scavenging assays (DPPH• and ABTS•+ tests), ferrous ions (Fe2+) chelating activity and reducing power assay (FRAP) were conducted. In all of the tests, the extracts exhibited strong antioxidant activity. Furthermore, in-vitro cytotoxic activity assays of the methanolic extracts showed potent cytotoxic effects against two breast cancer cell lines (MDA-MB-468 and MCF-7), with no cytotoxicity towards normal cells (PBMCs). Reactive oxygen species generation was presumed to be a potential reason for the observed cytotoxic effects. According to all the above, and considering its appropriate composition of mineral elements and phenolic compounds, Joo could offer a beneficial and natural source of bioactive compounds that can be either used on the preventive side as it could potentially be used in the clinic without toxicity.

Cytotoxicity of new pyridazin-3(2H)-one derivatives orchestrating oxidative stress in human triple-negative breast cancer (MDA-MB-468).

Triple-negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer characterized by high morbidity and mortality. In the absence of targeted therapy, only chemotherapy is available in this case of cancer. The current study investigated the antitumor effect of new pyridazin-3(2H)-one derivatives on the human TNBC cell line, MD-MB-468. The in vitro cytotoxic activities were investigated using the tetrazolium-based MTT assay. Lipid peroxidation, H2 O2 content, and the specific activities of antioxidant enzymes were also determined. Two molecules, 6f and 7h, were found to be selectively highly active against tumor cells with IC50 values of 3.12 and 4.9 µM, respectively. Furthermore, cells exposed to 6f showed a significant increase in H2 O2 and lipid peroxidation levels, accompanied by a decrease in the enzyme activities of glutathione reductase (GR) and thioredoxin reductase (TrxR). The cytotoxicity of the compound 6f may improve the therapeutic efficacy of the current treatment for TNBC via the inhibition of GR and TrxR activities.

Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells.

Metformin causes an AMP/ATP ratio increase and AMP-activated protein kinase (AMPK) activation. Since caveolin-1 (Cav-1) plays a role in AMPK activation and energy balance, we investigated whether Cav-1 could participate in metformin's inhibitory effect on IGF1 signaling. The effect of metformin was studied in two non-small-cell lung cancer (NSCLC) cell lines, Calu-1 and Calu-6, expressing higher and lower amounts of Cav-1, respectively. In Calu-1, but not in Calu-6 cells, metformin reduced phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR) substrates Akt and Forkhead transcription factor 3a (FOXO3a), inhibited IGF1-dependent FOXO3a nuclear exit, and decreased IGF1-dependent cell proliferation. Here, we show that sensitivity of NSCLC cells to metformin was dependent on Cav-1 expression and that metformin required Cav-1 to induce AMPK phosphorylation and AMP/ATP ratio increase. Cav-1 silencing in Calu-1 and overexpression in Calu-6 reduced and improved, respectively, the inhibitory effect of metformin on IGF1-dependent Akt phosphorylation. Prolonged metformin treatment in Calu-6 cells induced a dose-dependent expression increase of Cav-1 and OCT1, a metformin transporter. Cav-1 and OCT1 expression was associated with the antiproliferative effect of metformin in Calu-6 cells (IC(50)=18 mM). In summary, these data suggest that Cav-1 is required for metformin action in NSCLC cells.

The Natural Neuroprotective Compounds Used in the 6-Hydroxydopamine- Induced Parkinson's Disease in Zebrafish: The Current Applications and Perspectives.

BACKGROUND AND OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of the dopaminergic neurons in the substantia nigra pars compacta, resulting in the loss of dopamine in the striatum, leading thus to the PD classic movement symptoms: resting tremor, rigidity, and bradykinesia/akinesia. Furthermore, Levodopa's efficacy declines with long-term use, generating serious motor complications. Neuroprotection implies the use of different agents exhibiting various neuroprotective strategies to prevent brain degeneration and neuron loss. The present review aims to summarize and analyze the natural neuroprotective compounds that have been tested against PD induced by the 6-hydroxydopamine (6-OHDA) in zebrafish. RESULTS: The current study collected 23 different natural substances, divided into five distinct categories, namely herbal extracts, herbal formulations, bioactive compounds, marine products, and marine extracts. They modulate various signaling pathways involved in PD pathogenesis and exhibit specific activities such as an anxiolytic profile, improving locomotor impairment, restoring memory troubles, preventing DNA loss, inhibiting acetylcholinesterase, reducing lipid peroxidation and antiinflammatory activity, and enhancing the brain antioxidant enzymes. CONCLUSION AND PERSPECTIVES: This review discusses the most promising natural neuroprotective compounds that have been evaluated for their potential efficiency on the 6-OHDA-induced lesions in the zebrafish model. These natural substances deserve further consideration for determination of their optimum concentrations, bioavailability, and their ability to cross the blood-brain-barrier to exert their effects on PD. Furthermore, a complete understanding of the molecular mechanisms involved in PD and larger epidemiologic and randomized clinical trials in humans is also required.

In vitro evaluation of dioscin and protodioscin against ER-positive and triple-negative breast cancer.

Women's breast cancer is one of the most significant healthcare issues for the human race that demands a proactive strategy for a cure. In this study, the cytotoxic activity (MTT assay) of two natural steroidal compounds, protodioscin and dioscin, against two major subtypes of human breast cancer estrogen receptor-positive (ER-positive)/MCF-7 and triple-negative breast cancer (TNBC)/MDA-MB-468), was assessed. The clonogenic capacity was evaluated using the clonogenic assay. Oxidative stress was determined by measuring the formation of malondialdehyde and H2O2 and the assessment of total antioxidant enzyme activities (SOD, GPx, GR, and TrxR). Protodioscin and dioscin were highly cytotoxic against the tested cell lines (1.53 µM

Phytochemical profile and antioxidant capacity, α-amylase and α-glucosidase inhibitory activities of Oxalis pes-caprae extracts in alloxan-induced diabetic mice.

Diabetes and its complications are closely correlated with chronic hyperglycemia, causing severe oxidative stress and leading to glycation reaction with formation of advanced glycation end products. However, medicinal plants are still a source of inspiration for the discovery of new treatments of several diseases, including diabetes. The present study was aimed to evaluate the antioxidant and antidiabetic properties of Oxalis pes-caprae flowers extract in alloxan-induced diabetic mice. The phytochemical and antioxidant activities of both aqueous and methanolic extracts were assessed by in-vitro testing such as free radical scavenging assays (DPPH and ABTS+), ferrous ions (Fe2+) chelating activity and reducing power assay. Additionally, the detection of Amadori products and advanced glycation end products was used to determine the antiglycation potential. α-glucosidase and α-amylase inhibitory assessment was employed to determine the antidiabetic effect, while alloxan-induced diabetic mice were used to measure the in-vivo activities of antioxidants and carbohydrates enzymes. The effect of the methanolic extract on body weight and blood glucose level of extract-treated diabetic mice were also investigated. Among the tested extract, the methanolic extract was the richest in phenolic compounds which is directly related with their remarkable antioxidant, enzyme inhibitory and antiglycation activity. The oral administration of the two doses of Oxalis pes-caprae flowers (150 mg/kg and 250 mg/kg) daily for 3 weeks resulted in hypoglycemic effect compared to the reference drug, glibenclamide (10 mg/kg). Furthermore, the extract was shown to significantly increase the activities of antioxidants and glycolysis enzymes in the liver, kidney and spleen of diabetic mice, compared to diabetic control group. Therefore, Oxalis pes-caprae extract effectively exhibited hypoglycemic and antidiabetic effects as indicated by in-vitro and in-vivo studies, confirming the protective effects on hyperglycemia and oxidative damage.

Crataegus oxyacantha Extract as a Biostimulant to Enhance Tolerance to Salinity in Tomato Plants.

Salinity is a severe abiotic problem that has harmful impacts on agriculture. Recently, biostimulants were defined as bioprotectant materials that promote plant growth and improve productivity under various stress conditions. In this study, we investigated the effect of Crataegus oxyacantha extract as a biostimulant on tomato plants (Solanum lycopersicum) grown under salt stress. Concentrations of 20 mg/L, 30 mg/L, and 70 mg/L of C. oxyacantha extract were applied to tomato plants that were grown under salt stress. The results indicated that plants that were treated with C. oxyacantha extract had a higher ability to tolerate salt stress, as demonstrated by a significant (p < 0.05) increase in plant growth and photosynthetic pigment contents, in addition to a significant increase in tomato soluble sugars and amino acids compared to the control plants. In the stressed tomato plants, malondialdehyde increased and then decreased significantly with the different concentrations of C. oxyacantha extract. Furthermore, there was a significant improvement in the antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), and glutathione reductase (GR) in the stressed plants, especially after treatment with 70 mg/L of the extract. Overall, our results suggest that C. oxyacantha extract could be a promising biostimulant for treating tomato plants under salinity stress.

Thymoquinone Alleviates Cadmium Induced Stress in Germinated Lens culinaris Seeds by Reducing Oxidative Stress and Increasing Antioxidative Activities.

This study investigated the effect of thymoquinone on seeds germination and young seedlings of lentils under cadmium (Cd) stress (300 µM). Three different concentrations (10 µM, 1 µM, and 0.1 µM) of thymoquinone were applied. Our results indicated that thymoquinone has a positive effect on several physiological and biochemical parameters on seeds germination and young seedlings of lentils under Cd stress, which led to enhancing their growth. A significant increase in shoot and root length, fresh and dry weight, and chlorophyll content was observed in the treated plants compared to the control plants. However, the thymoquinone treatment significantly reduced malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents compared to untreated roots and seedlings under Cd-stress. Nevertheless, our results show that the thymoquinone significantly improved the activities of enzymes involved in antioxidant response, including superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), thioredoxin reductase (TrxR), and ascorbate peroxidase (APX). We have also studied the activities of isocitrate dehydrogenase (ICDH) and malate dehydrogenase (MDH); ICDH was increased significantly in roots and seedlings in the presence of different doses of thymoquinone. However, the activity MDH was increased only in roots. Our results suggest that the application of thymoquinone could mitigate cadmium induced oxidative stress.

Synergistic antioxidant effects of natural compounds on H2O2-induced cytotoxicity of human monocytes.

Natural compounds are endowed with a broad spectrum of biological activities, including protection against Toxins. Most of them are known for their antioxidant and radical scavenging activities. However, the synergistic combination of these natural molecules is not well studied. Therefore, the present study aims first to investigate the effect of four potent natural molecules [rosmarinic acid (Ros-A), ellagic acid (Ella-A), curcumin (Cur), and syringic acid (Syr-A)] on H2O2 -induced cell cytotoxicity and oxidative stress on the human monocytes (THP-1) and then to evaluate their combined action effect. Optimal combinations of these molecules were predicted using an augmented mixture design approach. In the first, as preliminary antioxidant activities screening, two in vitro assays were adopted to assess the single radicals scavenging activity of these natural compounds, DPPH• and ABTS• + tests. Based on the results obtained, the multitude of optimal formulas proposed by the mixture design study led to choosing four potent compositions (comp) in addition to ellagic acid, proposed as the most efficient when applied alone. The different molecules and mixtures were used to assess their cytoprotective effect on THP-1 cells in the presence and absence of H2O2. The most potent Comp-4, as well as the molecules forming this mixture, were exploited in a second experiment, aiming to understand the effect on oxidative stress via antioxidant enzyme activities analysis in the H2O2-induced oxidative stress in the THP-1 cell line. Interestingly, the natural molecules used for THP-1 cells treatment exhibited a significant increase in the antioxidant defense and glyoxalase system as well as suppression of ROS generation evaluated as MDA content. These results indicate that the natural compounds tested here, especially the synergistic effect of Cur and Ros-A (Comp-4), could serve as cytoprotective and immunostimulant agents against H2O2-induced cytotoxicity THP-1 cells, which makes them interesting for further investigations on the molecular mechanisms in preclinical animal models.

Synthesis and cytotoxicity against tumor cells of pincer N-heterocyclic ligands and their transition metal complexes.

The complexes: [CoL2](ClO4)2 (1), [FeL2](ClO4)2 (2), [NiL2](ClO4)2 (3) and [MnLCl2] (4), with L = diethyl-1,1'-(pyridine-2,6-diyl)bis(5-methyl-1H-pyrazole-3-carboxylate), were synthesized and fully characterized. Structural analysis revealed two distinct patterns influenced by the counter ions where L acts as a tridentate chelating ligand. The in vitro antitumor activity of L and L' (diethyl 2,2'-(pyridine-2,6-diylbis(5-methyl-1H-pyrazole-3,1-diyl)) diacetate) as well as their metal complexes, was tested by the measurement of their cytostatic and cytotoxic properties towards the blood cancer mastocytoma cell line P815. We have also investigated their interactions with the antioxidant enzyme system. As a result, [MnL'Cl2] (1') exhibited the strongest activity compared to reference cis-platin with no cytotoxicity towards normal cells PBMCs (Peripheral Blood Mononuclear Cells). On the other hand, the antioxidant enzyme activity showed that the efficiency of metal complex 1' against P815 tumor cells was via the rise in the SOD activity and inhibition of CAT enzyme activity. This proof of concept study allows disclosure of a new class of molecules in cancer therapeutics.

The Aqueous Extract from Ceratonia siliqua Leaves Protects Against 6-hydroxydopamine in Zebrafish: Understanding the Underlying Mechanism.

Ceratonia siliqua L. is a Mediterranean medicinal plant traditionally cultivated for its ethnopharmacological benefits, such as antidiarrheal, antidiabetic, enhance acetylcholine, antioxidant, antiatherosclerotic, and for its possible anti-neurodegenerative potential. The aim of the present study was to evaluate the chemical composition, as well as the cognitive-enhancing, anxiolytic, and antioxidant activities of the aqueous extract from C. siliqua (CsAE) leaves against 6-hydroxydopamine (6-OHDA) zebrafish Parkinson's disease (PD) model. CsAE (0.1, 0.3, and 1 mg/L) was administered by immersion to zebrafish (Danio rerio) for eight consecutive days and one hour before each behavioral test of each day, while 6-OHDA (250 µM) treatment was supplied one day before the novel tank diving test (NTT). Qualitative and quantitative analyses were performed by the ultra-high-performance liquid chromatography (UHPLC) analysis. The memory performance was evaluated through the NTT and Y-maze tests. Additionally, the in vitro and in vivo antioxidant status and acetylcholinesterase (AChE) activity was also assessed. Our finds demonstrated that CsAE presented positive antioxidant and anti-AChE activities, which contributed to the improvement of cognitive function in the 6-OHDA zebrafish PD model.