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.

Liquid-liquid phase separation of protein tau: An emerging process in Alzheimer's disease pathogenesis.

Metabolic reactions within cells occur in various isolated compartments with or without borders, the latter being known as membrane-less organelles (MLOs). The MLOs show liquid-like properties and are formed by a process known as liquid-liquid phase separation (LLPS). MLOs contribute to different molecules interactions such as protein-protein, protein-RNA, and RNA-RNA driven by various factors, such as multivalency of intrinsic disorders. MLOs are involved in several cell signaling pathways such as transcription, immune response, and cellular organization. However, disruption of these processes has been found in different pathologies. Recently, it has been demonstrated that protein aggregates, a characteristic of some neurodegenerative diseases, undergo similar phase separation. Tau protein is known as a major neurofibrillary tangles component in Alzheimer's disease (AD). This protein can undergo phase separation to form a MLO known as tau droplet in vitro and in vivo, and this process can be facilitated by several factors, including crowding agents, RNA, and phosphorylation. Tau droplet has been shown to mature into insoluble aggregates suggesting that this process may precede and induce neurodegeneration in AD. Here we review major factors involved in liquid droplet formation within a cell. Additionally, we highlight recent findings concerning tau aggregation following phase separation in AD, along with the potential therapeutic strategies that could be explored in this process against the progression of this pathology.

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.

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.

Anti-rheumatoid drugs advancements: New insights into the molecular treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of more than 100 types of arthritis. This chronic autoimmune disorder affects the lining of synovial joints in about 0.5% of people and may induce severe joints deformity and disability. RA impacts health life of people from all sexes and ages with more prevalence in elderly and women people. Significant improvement has been noted in the last two decades revealing the mechanisms of the development of RA, the improvement of the early diagnosis and the development of new treatment options. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs) remain the most known treatments used against RA. However, not all patients respond well to these drugs and therefore, new solutions are of immense need to improve the disease outcomes. In the present review, we discuss and highlight the recent findings concerning the different classes of RA therapies including the conventional and modern drug therapies, as well as the recent emerging options including the phyto-cannabinoid and cell- and RNA-based therapies. A better understanding of their mechanisms and pathways might help find a specific target against inflammation, cartilage damage, and reduce side effects in arthritis.

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.

Genetic diversity for agromorphological traits, phytochemical profile, and antioxidant activity in Moroccan sorghum ecotypes.

Sorghum, the fifth most important cereal crop, is a well-adapted cereal to arid/semi-arid regions. Sorghum is known for multiple end-uses as food, feed, fuel, forage, and as source of bioactive compounds that could be used for medical applications. Although the great improvement in the process of sorghum breeding, the average yield of this crop is still very low. Therefore, exploring the genetic diversity in sorghum accessions is a critical step for improving this crop. The main objective of the current work was to study the genetic variation existing in a Moroccan sorghum collection. Indeed, 10 sorghum ecotypes were characterized based on agromorphological descriptors. Both quantitative (25) and qualitative (7) traits revealed variability (p < 0.05) among the studied ecotypes. At the seedling stage, most of the ecotypes showed good to high vigor (70%). However, as the sorghum plants grow, the difference between genotypes become more apparent, especially at the generative phase. For instance, three different panicle shapes have been observed, erect (50%), semi-bent (30%), and bent (20%) with different degree of compactness (20% for loose, semi-compact, and compact panicles, and 30% for semi-loose panicles). In another part of this study, the phytochemical composition and antioxidant activities of the sorghum ecotypes have been determined. The results showed variable total phenolic contents, and total flavonoid contents ranging from 125.86 ± 1.36 to 314.91 ± 3.60 mg GAE/g dw and 114.0 ± 13.2 to 138.5 ± 10.8 (mg catechin equivalent/100 g, dw) respectively, with a differential antioxidant activities as well. These results indicate that for any crop breeding program, it is preferable to take into consideration both morphological and biochemical traits for a better selection of high yielding varieties with high added value compounds. Therefore, the implication of these results in the context of sorghum breeding activities could be a resourceful option for farmers.

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.