Evaluation of Cisplatin-Induced Acute Renal Failure Amelioration Using Fondaparinux and Alteplase.

Acute renal failure (ARF) is a deleterious condition with increased mortality or healthcare costs or dialysis-dependent end-stage renal disease. The study aims to compare prophylaxis with fondaparinux (Fund) vs. treatment with alteplase (Alt) in ameliorating cisplatin (Cis)-induced ARF. Sixty male mice were equally divided randomly into six groups of control, Cis, Alt, and Cis + Alt groups receiving normal saline for 10 days. All four groups except for the control received Cis (30 mg/kg, i.p.) on day 7, and 6 h later, both the Alt groups received Alt (0.9 mg/kg, i.v.). The animal groups Fund and Fund + Cis received Fund (5 mg/kg, i.p.) for 10 days, and the Fund + Cis group on day 7 received Cis. All the animal groups were euthanized 72 h after the Cis dose. The Fund + Cis group showed significantly increased expression levels of platelet count, retinoid X receptor alpha (RXR-α) and phosphorylated Akt (p-Akt) in addition to decreased levels of urea, blood urea nitrogen (BUN), uric acid, white blood cells (WBCs), red blood cells (RBCs), relative kidney body weight, kidney injury score, glucose, prothrombin (PT), A Disintegrin And Metalloproteinases-10 (ADAM10), extracellular matrix deposition, protease-activated receptor 2 (PAR-2), and fibrinogen expression when compared to the Cis-only group. Meanwhile, the Cis + Alt group showed increased caspase-3 expression in addition to decreased levels of urea, BUN, uric acid, WBCs, RBCs, glucose, platelet count and PT expression with a marked decrease in PAR-2 protein expression compared to the Cis group. The creatinine levels for both the Fund + Cis and Cis + Alt groups were found to be comparable to those of the Cis-only group. The results demonstrate that the coagulation system's activation through the stimulation of PAR-2 and fibrinogen due to Cis-induced ADAM10 protein expression mediated the apoptotic pathway, as indicated by caspase-3 expression through the p-Akt pathway. This is normally accompanied by the loss of RXR-α distal and proximal tubules as lipid droplets. When the animals were pre-treated with the anticoagulant, Fund, the previous deleterious effect was halted while the fibrinolytic agent, Alt, most of the time failed to treat Cis-induced toxicity.

In Vivo and In Silico Analgesic Activity of Ficus populifolia Extract Containing 2-O-ß-D-(3',4',6'-Tri-acetyl)-glucopyranosyl-3-methyl Pentanoic Acid.

Natural product-based structural templates have immensely shaped small molecule drug discovery, and new biogenic natural products have randomly provided the leads and molecular targets in anti-analgesic activity spheres. Pain relief achieved through opiates and non-steroidal anti-inflammatory drugs (NSAIDs) has been under constant scrutiny owing to their tolerance, dependency, and other organs toxicities and tissue damage, including harm to the gastrointestinal tract (GIT) and renal tissues. A new, 3',4',6'-triacetylated-glucoside, 2-O-ß-D-(3',4',6'-tri-acetyl)-glucopyranosyl-3-methyl pentanoic acid was obtained from Ficus populifolia, and characterized through a detailed NMR spectroscopic analysis, i.e., 1H-NMR, 13C-DEPT-135, and the 2D nuclear magnetic resonance (NMR) correlations. The product was in silico investigated for its analgesic prowess, COX-2 binding feasibility and scores, drug likeliness, ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties, possible biosystem's toxicity using the Discovery Studio®, and other molecular studies computational software programs. The glycosidic product showed strong potential as an analgesic agent. However, an in vivo evaluation, though at strong levels of pain-relieving action, was estimated on the compound's extract owing to the quantity and yield issues of the glycosidic product. Nonetheless, the F. populifolia extract showed the analgesic potency in eight-week-old male mice on day seven of the administration of the extract's dose in acetic acid-induced writhing and hot-plate methods. Acetic acid-induced abdominal writhing for all the treated groups decreased significantly (p < 0.0001), as compared to the control group (n = 6) by 62.9%, 67.9%, and 70.9% of a dose of 100 mg/kg (n = 6), 200 mg/kg (n = 6), and 400 mg/kg (n = 6), respectively. Similarly, using the analgesia meter, the reaction time to pain sensation increased significantly (p < 0.0001), as compared to the control (n = 6). The findings indicated peripheral and central-nervous-system-mediated analgesic action of the product obtained from the corresponding extract.

Topical Eucalyptol Ointment Accelerates Wound Healing and Exerts Antioxidant and Anti-Inflammatory Effects in Rats' Skin Burn Model.

Eucalyptol is a major volatile constituent among well-known wound healing medicinal plants. The current study evaluated eucalyptol wound healing activity in the rat's third-degree skin-burn model. The parameters, i.e., skin-healing, oxidative/antioxidant markers, pro-/anti-inflammatory markers, were evaluated after 1- and 2-weeks of treatment regimens with 5% eucalyptol ointment. Eucalyptol-loaded ointment base of 5% w/w strength was formulated using fusion method and physically evaluated for consistency, stability, and homogeneity. A 25-rats were divided randomly into intact, negative control (untreated), silver sulfadiazine (SS, positive control), 1-week, and 2-weeks treated eucalyptol groups. Using an aluminum cylinder (120℃, 10 second duration), 3rd-degree skin burns were created on the rat's dorsum. Skin biopsies were collected at the end of the experiment for biochemical and histological investigations. Compared to the negative group; time-dependent wound size reduction and decreased edema were observed in eucalyptol-treated animals. Histopathological examinations demonstrated epidermis integrity, decreased neutrophil, and increased capillaries number in the 2-weeks and SS groups, compared to the negative and 1-week treated eucalyptol groups. Compared to the untreated animals, the 1- and 2-weeks eucalyptol treated groups' demonstrated significantly increased antioxidant superoxide dismutase (SOD, p=0.002 and p=0.003, respectively) and reduced lipid peroxide (LP, p=0.005 and p=0.0006, respectively). However, a significant increment of catalase (CAT, p=0.0009) was found only in the 2-weeks of eucalyptol group at a level of 2.42 ± 0.39 ng/g compared to 1.14 ± 0.04 ng/g in the untreated animals. Also, significant reductions in the cytokines, IL-1b, IL-6, and TNF-α (p < 0.05); and increase in the pro-angiogenic marker, IL-10, were detected in the 2-weeks (p=0.001) and SS (p=0.002) treated animals compared to the negative and 1-week eucalyptol treated groups. The study concluded that eucalyptol induced significant duration-based wound healing properties attributed to its antioxidant and anti-inflammatory effects.

Modification of SWCNTs with hybrid materials ZnO-Ag and ZnO-Au for enhancing bactericidal activity of phagocytic cells against Escherichia coli through NOX2 pathway.

Zinc oxide-silver (ZnO-Ag), and zinc oxide-gold (ZnO-Au) nano-composites were prepared through wet chemical process and laced into single-walled carbon nanotubes (SWCNTs) to yield ZnO-Ag-SWCNTs, and ZnO-Au-SWCNTs hybrids. These nano-composite-laced SWCNTs hybrids were characterized using Raman spectroscopic, X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analyses. The hybrids were evaluated for their effects on phagocytic cells and bactericidal activity against the gram-negative bacteria E. coli. Their phagocytic cell activities and intracellular killing actions were found to be significantly increased, as the ZnO-Ag-SWCNTs and ZnO-Au-SWCNTs nano-hybrids induced widespread clearance of Escherichia coli. An increase in the production of reactive oxygen species (ROS) also led to upregulated phagocytosis, which was determined mechanistically to involve the phagocyte NADPH oxidase (NOX2) pathway. The findings emphasized the roles of ZnO-Ag- and ZnO-Au-decorated SWCNTs in the prevention of bacterial infection by inhibiting biofilm formation, showing the potential to be utilized as catheter coatings in the clinic.

Cinnamaldehyde-Based Self-Nanoemulsion (CA-SNEDDS) Accelerates Wound Healing and Exerts Antimicrobial, Antioxidant, and Anti-Inflammatory Effects in Rats' Skin Burn Model.

Cinnamaldehyde, the main phytoconstituent of the cinnamon oil, has been reported for its potential wound healing activity, associated to its antimicrobial and anti-inflammatory effects. In this study, we are reporting on the cinnamaldehyde-based self-nanoemulsifying drug delivery system (CA-SNEDDS), which was prepared and evaluated for its antimicrobial, antioxidant, anti-inflammatory, and wound healing potential using the rat third-degree skin injury model. The parameters, i.e., skin healing, proinflammatory, and oxidative/antioxidant markers, were evaluated after 3 weeks of treatment regimens with CA-SNEDDS. Twenty rats were divided randomly into negative control (untreated), SNEDDS control, silver sulfadiazine cream positive control (SS), and CA-SNEDDS groups. An aluminum cylinder (120 °C, 10-s duration) was used to induce 3rd-degree skin burns (1-inch square diameter each) on the rat's dorsum. At the end of the experiment, skin biopsies were collected for biochemical analysis. The significantly reduced wound size in CA-SNEDDS compared to the negative group was observed. CA-SNEDDS-treated and SS-treated groups demonstrated significantly increased antioxidant biomarkers, i.e., superoxide dismutase (SOD) and catalase (CAT), and a significant reduction in the inflammatory marker, i.e., NAP-3, compared to the negative group. Compared to SNEDDS, CA-SNEDDS exhibited a substantial antimicrobial activity against all the tested organisms at the given dosage of 20 µL/disc. Among all the tested microorganisms, MRSA and S. typhimurium were the most susceptible bacteria, with an inhibition zone diameter (IZD) of 17.0 ± 0.3 mm and 19.0 ± 0.9 mm, respectively. CA-SNEDDS also exhibited strong antifungal activity against C. albicans and A. niger, with IZD of 35.0 ± 0.5 mm and 34.0 ± 0.5 mm, respectively. MIC and MBC of CA-SNEDDS for the tested bacteria ranged from 3.125 to 6.25 µL/mL and 6.25 to 12.5 µL/mL, respectively, while the MIC and MBC for C. albicans and A. niger were 1.56 µL/mL and 3.125 µL/mL, respectively. The MBIC and MBEC of CA-SNEDDS were also very significant for the tested bacteria and ranged from 6.25 to 12.5 µL/mL and 12.5 to 25.0 µL/mL, respectively, while the MBIC and MBEC for C. albicans and A. niger were 3.125 µL/mL and 6.25 µL/mL, respectively. Thus, the results indicated that CA-SNEDDS exhibited significant wound healing properties, which appeared to be attributed to the formulation's antimicrobial, antioxidant, and anti-inflammatory effects.

Galangin/ß-Cyclodextrin Inclusion Complex as a Drug-Delivery System for Improved Solubility and Biocompatibility in Breast Cancer Treatment.

The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble ß-cyclodextrin-epichlorohydrin (ß-CD), as an effective drug carrier to enhance the poor solubility and bioavailability of galangin (GAL), a poorly water-soluble model drug. In this regard, inclusion complexes of GAL/ß-CDP were prepared. UV-VIS spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), X-ray crystallography (XRD), zeta potential analysis, particle size analysis, field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM) were applied to characterize the synthesized GAL/ß-CD. Michigan Cancer Foundation-7 (MCF-7; human breast cancer cells) and rat embryo fibroblast (REF; normal cells) were employed to examine the in vitro cytotoxic effects of GAL/ß-CD using various parameters. The dye-based tests of MTT and crystal violet clearly exhibited that GAL/ß-CD-treated cells had a reduced proliferation rate, an influence that was not found in the normal cell line. The cells' death was found to follow apoptotic mechanisms, as revealed by the dye-based test of acridine orange/ethidium bromide (AO/EtBr), with the involvement of the mitochondria via caspase-3-mediated events, as manifested by the Rh 123 test. We also included a mouse model to examine possible in vivo toxic effects of GAL/ß-CD. It appears that the inclusion complex does not have a significant influence on normal cells, as indicated by serum levels of kidney and liver enzymatic markers, as well as thymic and splenic mass indices. A similar conclusion was reached on the histological level, as manifested by the absence of pathological alterations in the liver, kidney, thymus, spleen, heart, and lung.

Synthesis and Anti-Cancer Activity of New Pyrazolinyl-Indole Derivatives: Pharmacophoric Interactions and Docking Studies for Identifying New EGFR Inhibitors.

Newly designed series of indole-containing pyrazole analogs, pyrazolinylindoles, were synthesized, and their structures were confirmed based on the spectral data of the 1H NMR, 13C NMR, and HR-MS analyses. Preliminary anti-cancer activity testings were carried out by the National Cancer Institute, United States of America (NCI, USA). Compounds HD02, HD05, and HD12 demonstrated remarkable cytotoxic activities against nine categories of cancer types based cell line panels which included leukemia, colon, breast, melanoma, lungs, renal, prostate, CNS, and ovarian cancer cell lines. The highest cytotoxic effects were exhibited by the compounds HD02 [1-(5-(1-H-indol-3-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenylethanone], HD05 [1-(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenoxyethanone], and HD12 [(3-(4-chlorophenyl)-5-(1H-indol-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanone] against some of the 56 types of NCI-based cell lines in different panels. Compound HD05 showed the maximum range of cancer cell growth inhibitions against all categories of the cell lines in all nine panels. On average, in comparison to the referral standard, imatinib, at a dose level of 10 µM, the HD05 showed significant activity against leukemia in the range of 78.76%, as compared to the imatinib at 9% of cancer cells' growth inhibitions. Molecular docking simulation studies were performed in silico on the epidermal growth factor receptor (EGFR) tyrosine kinase, in order to validate the activity.

Copper Oxide Nanoparticle-Decorated Carbon Nanoparticle Composite Colloidal Preparation through Laser Ablation for Antimicrobial and Antiproliferative Actions against Breast Cancer Cell Line, MCF-7.

Copper oxide (CuO) nanoparticle- (NP-) decorated carbon NPs (CNPs) were produced as colloidal suspension through pulsed laser ablation technique in liquid (PLAL) medium. The antimicrobial activity of the produced NPs was tested against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), and anticancer activity was tested against breast cancer cell line, MCF-7, together with the biocompatibility assessment of these NPs. The X-ray diffraction (XRD) patterns of the obtained CNPs showed peaks at 26.58° and 43.78° (2θ) identical to (002) and (111) planes, respectively, of the carbon phases. It also displayed new peaks at 38.5° and 48.64° (2θ) after doping with CuO NPs. Transmission electron microscope (TEM) images revealed the crystalline nature with the spherical shape of the prepared CNPs with 5-40 nm diameter ranges. In addition, the NP effects on the bacterial cell walls and nucleic acid were confirmed using a scanning electron microscope (SEM) and microscopic fluorescence analysis. The NPs showed antibacterial activity through SEM examinations against the pathogenic microbial species, S. aureus and E. coli. In the cellular material release assay, the optical density of the bacterial cells, treated with NPs, displayed a significant increase with the time of exposure to NPs, and the cytotoxicity reached more than 80% of the level for the CNPs decorated with CuO NPs. The morphology of the MCF-7 cells treated with NPs decreased numbers, and the loss of contact with the surrounding cells was observed. These results confirmed that the CNPs decorated with CuO NPs have no observable side effects and can be safely used for therapeutic applications. It is also noteworthy that it is the first report of preparation of CuO NPs decorated with CNPs (CuO NPs-CNPs) by PLAL, and the produced NPs showed antimicrobial antiproliferative activities against breast cancer cell lines, MCF-7. The main advantage of the PLAL technique of synthesizing CuO NPs-CNPs provided a two-step, cost-effective, and eco-friendly method.

Bio-Evaluation of the Wound Healing Activity of Artemisia judaica L. as Part of the Plant's Use in Traditional Medicine; Phytochemical, Antioxidant, Anti-Inflammatory, and Antibiofilm Properties of the Plant's Essential Oils.

Artemisia judaica (ArJ) is a Mediterranean aromatic plant used traditionally to treat gastrointestinal ailments, skin diseases, atherosclerosis, and as an immuno-stimulant. This study describes ArJ essential oil constituents and investigates their wound healing activity. The in vitro antioxidant and antibiofilm activities of ArJ essential oil were investigated. The in vivo pro/anti-inflammatory and oxidative/antioxidant markers were compared with standard silver sulfadiazine (SS) in a second-degree skin burn experimental rat model. The gas chromatography-equipped flame ionization detector (GC-FID) analysis of ArJ essential oil revealed the major classes of compounds as oxygenated monoterpenes (>57%) and cinnamic acid derivatives (18.03%). The antimicrobial tests of ArJ essential oil revealed that Bacillus cereus, Candida albicans, and Aspergillus niger were the most susceptible test organisms. Two second-degree burns (each 1 inch square in diameter) were created on the dorsum of rats using an aluminum cylinder heated to 120 °C for 10 s. The wounds were treated either with ArJ or SS ointments for 21 days, while the negative control remained untreated, and biopsies were obtained for histological and biochemical analysis. The ArJ group demonstrated a significant increase in antioxidant superoxide dismutase (SOD) and catalase (CAT) enzymatic activities, while lipid peroxide (LP) levels remained insignificant compared to the negative control group. Additionally, ArJ and SS groups demonstrated a significant decrease in inflammatory levels of tumor necrosis factor α (TNF-α) compared to the negative group, while interleukin 1 beta (IL-1b) and IL-6 were comparable to the negative group. At the same time, anti-inflammatory IL-10 and transforming growth factor beta 1 (TGF-b1) markers increased significantly in the ArJ group compared to the negative control. The ArJ results demonstrated potent wound healing effects, comparable to SS, attributable to antioxidant and anti-inflammatory effects as well as a high proportion of oxygenated monoterpenes and cinnamate derivatives.

Preparation of Iron Oxide and Titania-Based Composite, Core-Shell Populated, Nanoparticulates Material by Two-Step LASER Ablation in Aqueous Media as Antimicrobial and Anticancer Agents.

Iron oxide and titania-based composite nanoparticles (NPs) populated with core-shell structures, as part of the mixture of the monometallic NPs, were prepared in water medium by the two-fluence LASER ablation technique by applying 30 and 60 mJ/cm2 LASER energy irradiations. The prepared monometallics, composite, and core-shell NPs structures were confirmed from the XRD, TEM, and EDX analyses, followed by the FE-SEM and UV absorptions. Optically, the NPs exhibited an increase in the energy gap from 3.27 eV to 3.75 eV as LASER fluence increased from 30 mJ/cm2 to 60 mJ/cm2. The average NPs core size distributions for the core-shell material ranged at ∼70 nm with the shell thickness around 20 nm. The biggest NPs were of ∼170 nm size which were sparsely distributed. The magnetization behaviors of the NPs were also investigated using the vibrating sample magnetometer (VSM). The NPs showed antimicrobial activities against the pathogenic species: Escherichia coli and Staphylococcus aureus. The antimicrobial activities of the synthesized NPs, synthesized under the influence of magnetic fields, were found to be more potent than the NPs synthesized without the presence of any magnetic field. The NPs prepared under the influence of the magnetic fields also comparatively exhibited higher levels of cytotoxicity against lung cancer cell lines (A549) than the NPs prepared under no magnetic field's influence by the similar energy level effects of the LASER fluence. The flow cytometry analyses confirmed the NPs' cytotoxic impacts against the human lung cancer A549 cell lines through the initiation of apoptosis and promotion of the cell cycle arrest at the G1 phase of cell division. To further confirm the cytotoxic effects and the mechanism of the anticancer activity of the synthesized NPs against the A549 cell lines, several related parameters (cell viability, membrane permeability, nuclear intensity, and cytochrome-C release) were analyzed using the high-content screening (HCS) assay. The study suggested that the prepared NPs have potential as antimicrobial and also as anti-lung-cancer agents as tested in vitro. These NPs can also be part of combined chemotherapy in different oncological interventions, as well as a sonosensitizer in sonomagnetic heating-based therapy, especially for cancers.

Sage, Salvia officinalis L., Constituents, Hepatoprotective Activity, and Cytotoxicity Evaluations of the Essential Oils Obtained from Fresh and Differently Timed Dried Herbs: A Comparative Analysis.

Sage, Salvia officinalis L., is used worldwide as an aromatic herb for culinary purposes as well as a traditional medicinal agent for various ailments. Current investigations exhibited the effects of extended dryings of the herb on the yields, composition, oil quality, and hepatoprotective as well as anti-cancer biological activities of the hydrodistillation-obtained essential oils from the aerial parts of the plant. The essential oils' yields, compositions, and biological activities levels of the fresh and differently timed and room-temperature dried herbs differed significantly. The lowest yields of the essential oil were obtained from the fresh herbs (FH, 631 mg, 0.16%), while the highest yield was obtained from the two-week dried herbs (2WDH, 1102 mg, 0.28%). A notable decrease in monoterpenes, with increment in the sesquiterpene constituents, was observed for the FH-based essential oil as compared to all the other batches of the essential oils obtained from the different-timed dried herbs. Additionally, characteristic chemotypic constituents of sage, i.e., α-pinene, camphene, ß-pinene, myrcene, 1, 8-cineole, α-thujone, and camphor, were present in significantly higher proportions in all the dried herbs' essential oils as compared to the FH-based essential oil. The in vivo hepatoprotective activity demonstrated significant reductions in the levels of AST, ALT, and ALP, as well as a significant increase in the total protein (p < 0.05) contents level, as compared to the acetaminophen (AAP) administered experimental group of rats. A significant reduction (p < 0.05) in the ALT level was demonstrated by the 4WDH-based essential oil in comparison to the FH-based essential oil. The levels of creatinine, cholesterol, and triglycerides were reduced (p < 0.05) in the pre-treated rats by the essential oil batches, with non-significant differences found among them as a result of the herbs dryings based oils. A notable increase in the viability of the cells, and total antioxidant capacity (TAOxC) levels, together with the reduction in malondialdehyde (MDA) levels were observed by the essential oils obtained from all the batches as compared with the AAP-treated cell-lines, HepG-2, HeLa, and MCF-7, that indicated the in vitro hepatoprotective effects of the sage essential oils. However, significant improvements in the in vivo and in vitro hepatoprotective activities with the 4WDH-based oil, as compared to all other essential oil-batches and silymarin standard demonstrated the beneficial effects of the drying protocol for the herb for its medicinal purposes.

Comparative Phytochemical Profile and Biological Activity of Four Major Medicinal Halophytes from Qassim Flora.

Four halophytic plants, Lycium shawii, Anabasis articulata, Rumex vesicarius, and Zilla spinosa, growing in the central Qassim area, Saudi Arabia, were phytochemically and biologically investigated. Their hydroalcoholic extracts' UPLC-ESIQ-TOF analyses demonstrated the presence of 44 compounds of phenolic acids, flavonoids, saponins, carbohydrates, and fatty acids chemical classes. Among all the plants' extracts, L. shawii showed the highest quantities of total phenolics, and flavonoids contents (52.72 and 13.01 mg/gm of the gallic acid and quercetin equivalents, respectively), along with the antioxidant activity in the TAA (total antioxidant activity), FRAP (ferric reducing antioxidant power), and DPPH-SA (2,2-diphenyl-1-picryl-hydrazyl-scavenging activity) assays with 25.6, 56.68, and 19.76 mg/gm, respectively, as Trolox equivalents. The hydroalcoholic extract of the L. shawii also demonstrated the best chelating activity at 21.84 mg/gm EDTA equivalents. Among all the four halophytes, the hydroalcoholic extract of L. shawii exhibited the highest antiproliferative activity against MCF7 and K562 cell lines with IC50 values at 194.5 µg/mL and 464.9 µg/mL, respectively. The hydroalcoholic extract of A. articulata demonstrated better cytotoxic activity amongst all the tested plants' extracts against the human pancreatic cancer cell lines (PANC1) with an IC50 value of 998.5 µg/mL. The L. shawii induced apoptosis in the MCF7 cell lines, and the percentage of the necrotic cells changed to 28.1% and 36.5% for the IC50 and double-IC50 values at 22.9% compared with the untreated groups. The hydroalcoholic extract of L. shawii showed substantial antibacterial activity against Bacillus cereus ATCC 10876 with a MIC value of 12.5 mg/mL. By contrast, the A. articulata and Z. spinosa exhibited antifungal activities against Aspergillus niger ATCC 6275 with MIC values at 12.5 and 50 mg/mL, respectively. These findings suggested that the L. shawii is a potential halophyte with remarkable biological properties, attributed to its contents of phenolics and flavonoid classes of compounds in its extract.

Roles of Suaeda vermiculata Aqueous-Ethanolic Extract, Its Subsequent Fractions, and the Isolated Compounds in Hepatoprotection against Paracetamol-Induced Toxicity as Compared to Silymarin.

Suaeda vermiculata, a halophyte consumed by livestock, is also used by Bedouins to manage liver disorders. The aqueous-ethanolic extract of S. vermiculata, its subsequent fractions, and pure compounds, i.e., pheophytin-A (1), isorhamnetin-3-O-rutinoside (2), and quercetin (3), were evaluated for their hepatoprotective efficacy. The male mice were daily fed with either silymarin, plant aq.-ethanolic extract, fractions, pure isolated compounds, or carboxyl methylcellulose (CMC) for 7 days (n = 6/group, p.o.). On the day 7th of the administrations, all, except the intact animal groups, were induced with hepatotoxicity using paracetamol (PCM, 300 mg/kg). The anesthetized animals were euthanized after 24 h; blood and liver tissues were collected and analysed. The serum aspartate transaminase (AST) and alanine transaminase (ALT) levels decreased significantly for all the S. vermiculata aq.-ethanolic extract, fraction, and compound-treated groups when equated with the PCM group (p < 0.0001). The antioxidant, superoxide dismutase (SOD), increased significantly (p < 0.05) for the silymarin-, n-hexane-, and quercetin-fed groups. Similarly, the catalase (CAT) enzyme level significantly increased for all the groups, except for the compound 2-treated group as compared to the CMC group. Also, the glutathione reductase (GR) levels were significantly increased for the n-butanol treated group than for the PCM group. The oxidative stress biomarkers, lipid peroxide (LP) and nitric oxide (NO), the inflammatory markers, IL-6 and TNF-α, and the kidney's functional biomarker parameters remained unchanged and did not differ significantly for the treated groups in comparison to the PCM-induced toxicity bearing animals. All the treated groups demonstrated significant decreases in cholesterol levels as compared to the PCM group, indicating hepatoprotective and antioxidant effects. The quercetin-treated group demonstrated significant improvement in triglyceride level. The S. vermiculata aq.-ethanolic extract, fractions, and the isolated compounds demonstrated their hepatoprotective and antioxidant effects, confirming the claimed traditional use of the herb as a liver protectant.

Chemical Profile, Antioxidant, Antimicrobial, and Anticancer Activities of the Water-Ethanol Extract of Pulicaria undulata Growing in the Oasis of Central Saudi Arabian Desert.

Pulicaria undulata (L.) C. A. Mey has multiple uses as part of the traditional medicament, and several biological activities of the plant have been corroborated in the scientific literature. The current work evaluates the phytochemical constituents and biological properties of the water-ethanol extract of the P. undulata growing in Qassim, the central arid regions of the Kingdom of Saudi Arabia. Qualitative UPLC-ESIQ-TOF analysis identified 27 compounds belonging to the phenolics, flavonoids, triterpenes, coumarins, and of fatty acids chemical classes. The quantitative analysis exhibited 33.3 mg/g GAE (Gallic Acid Equivalents), and 10.8 mg/g QE (Quercetin Equivalents) of the phenolics and flavonoids in the plant's concentrated (to dryness) water-ethanol extract. The trace elements analysis of the plant's dry powder established the presence of copper (20.13 µg/kg), and zinc (68.2 µg/kg) in the higher levels of occurrences. In terms of the antioxidant potential of the plant's extract, the ferric-reducing, and free-radicals scavenging activities were recorded at 47.11 mg/g, and 19.13 mg/g equivalents of the concentrated to dryness water-ethanol extract of the plant. The water-ethanol extract of P. undulata also exhibited antimicrobial activity against the tested Gram-positive bacteria, while no activity was observed against the tested Gram-negative bacteria, or the fungi. The MIC (minimum inhibitory concentration) values were in the range of 49 to 1563 µg/mL, whereas the MBC (minimum bactericidal concentration) values ranged from 49 to 3125 µg/mL, against the tested Gram-positive bacteria. The P. undulata water-ethanol extract also exhibited potent cytotoxic effects with the IC50 value at 519.2 µg/mL against the MCF-7 breast cancer cell-lines, followed by the anticancer activity of erythroleukemic cell-lines, K562 at 1212 µg/mL, and pancreatic cell-lines, PANC-1, at 1535 µg/mL, as compared to the normal fibroblast cells (4048 µg/mL). The Annexin-V assay demonstrated that, as the P. undulata extract's dose increased from IC50 to twice of the IC50, the percentage of the necrosis was found to be increased in the late apoptosis stage of the cancer cells. These data confirmed the P. undulata extract's ability to inhibit several human cancer cell lines' growth in comparison to other local halophytes. The antimicrobial activity of the plant was also confirmed.

Layer-by-Layer Nanoparticles of Tamoxifen and Resveratrol for Dual Drug Delivery System and Potential Triple-Negative Breast Cancer Treatment.

Nanoparticle development demonstrates use in various physicochemical, biological, and functional properties for biomedical applications, including anti-cancer applications. In the current study, a cancer therapeutic conjugate was produced consisting of tamoxifen (TAM) and resveratrol (RES) by layer-by-layer (LbL) nanoparticles based on lipid-based drug delivery systems and liquid crystalline nanoparticles (LCNPs) coated with multiple layers of positively charged chitosan and negatively charged hyaluronic acid for the evaluation of biocompatibility and therapeutic properties against cancer cells. Multiple techniques characterized the synthesis of TAM/RES-LbL-LCNPs, such as Fourier-transform infrared spectroscopy (FTIR), X-ray crystallography (XRD), Zeta potential analysis, particle size analysis, Field Emission Scanning Electron Microscope (FESEM), and Transmission electron microscopy (TEM). The in vitro cytotoxic effects of TAM/RES-LbL-LCNPs were investigated against human breast cancer cell line, Michigan Cancer Foundation-7 (MCF-7), and human triple-negative breast cancer cell line, Centre Antoine Lacassagne-51 (CAL-51), using various parameters. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed that the treatment of cells with TAM/RES-LbL-LCNPs caused a reduction in cell proliferation, and no such inhibition was observed with human normal liver cell line: American Type Culture Collection Cell Line-48 (WRL-68 [ATCC CL-48]). Fluorescent microscopy examined the ability of Fluorescein isothiocyanate (FITC) to bind to TAM/RES-LbL-LCNPs along with their cellular uptake. Apoptosis determination was performed using hematoxylin-eosin and acridine orange-propidium iodide double staining. The expression of P53 and caspase-8 was analyzed by flow cytometry analysis. An in vivo study determined the toxicity of TAM/RES-LbL-LCNPs in mice and assessed the functional marker changes in the liver and kidneys. No significant statistical differences were found for the tested indicators. TAM/RES-LbL-LCNP treatment showed no apparent damages or histopathological abnormalities in the heart, lung, liver, spleen, and kidney histological images. The current findings observed for the first time propose that TAM/RES-LbL-LCNPs provide a new and safer method to use phytochemicals in combinatorial therapy and provide a novel treatment approach against breast cancers.

Quercetin against MCF7 and CAL51 breast cancer cell lines: apoptosis, gene expression and cytotoxicity of nano-quercetin.

Aims: To evaluate the anti breast-cancer activity, biocompatibility and toxicity of poly(d,l)-lactic-co-glycolic acid (PLGA)-encapsulated quercetin nanoparticles (Q-PLGA-NPs). Materials & methods: Quercetin was nano-encapsulated by an emulsion-diffusion process, and the nanoparticles were fully characterized through Fourier transform infrared spectroscopy, x-ray diffractions, FESEM and zeta-sizer analysis. Activity against CAL51 and MCF7 cell lines were assessed by DNA fragmentation assays, fluorescence microscopy, and acridine-orange, and propidium-iodide double-stainings. Biocompatibility towards red blood cells and toxicity towards mice were also explored. Results: The Q-PLGA-NPs exhibited apoptotic activity against the cell lines. The murine in vivo studies showed no significant alterations in the liver and kidney's functional biomarkers, and no apparent abnormalities, or tissue damages were observed in the histological images of the liver, spleen, lungs, heart and kidneys. Conclusion: The study established the preliminary in vitro efficacy and in vivo safety of Q-PLGA-NPs as a potential anti-breast cancer formulation.

Lay abstract Quercetin is a flavonoid, a type of chemical, antioxidant in nature, found in many fruits and vegetables. It is known to have anticancer properties. In this study, quercetin was encased into nano-sized particles of biologically compatible and bio-degradable synthetic polymer, named PLGA (poly-[D,L]-lactic-co-glycolic acid). The effects of the quercetin nanoparticles/nano-quercetin were tested against two types of breast cancer cell lines in the laboratory. The quercetin-loaded nanoparticles were able to kill the breast cancer cells, suggesting they could be able to kill the cancer cells in the body. Also, when given to mice, the quercetin nanoparticles did not appear to damage any organ, or change the functions of the liver, and kidneys, thereby suggesting that they are not toxic. Further work is required to assess how well they could be used to treat breast cancer in people.

Gold Nanoparticles and Graphene Oxide Flakes Enhance Cancer Cells' Phagocytosis through Granzyme-Perforin-Dependent Biomechanism.

The study aimed to investigate the roles of gold nanoparticles (GNPs) and graphene oxide flakes (GOFs) as phagocytosis enhancers against cancer cells. The nanomaterials were characterized through SEM and UV-VIS absorptions. The GNPs and GOFs increased the macrophages' phagocytosis ability in engulfing, thereby annihilating the cancer cells in both in vitro and in vivo conditions. The GNPs and GOFs augmented serine protease class apoptotic protein, granzyme, passing through the aquaporin class protein, perforin, with mediated delivery through the cell membrane site for the programmed, calibrated, and conditioned cancer cells killing. Additionally, protease inhibitor 3,4-dichloroisocoumarin (DCI) significantly reduced granzyme and perforin activities of macrophages. The results demonstrated that the GOFs and GNPs increased the activation of phagocytic cells as a promising strategy for controlling cancer cells by augmenting the cell mortality through the granzyme-perforin-dependent mechanism.

Phytochemical Analysis, Pharmacological and Safety Evaluations of Halophytic Plant, Salsola cyclophylla.

Salsola cyclophylla, an edible halophyte, is traditionally used for inflammation and pain. To confirm the claimed anti-inflammatory and analgesic properties, a detailed study on respective pharmacological actions was undertaken. The activities are contemplated to arise from its phytoconstituents. The LC-MS analysis of S. cyclophylla 95% aqueous-ethanolic extract revealed the presence of 52 compounds belonging to phenols, flavonoids, coumarins, and aliphatics class. A high concentration of Mn, Fe, and Zn was detected by atomic absorption spectroscopic analysis. The ethyl acetate extract showed the highest flavonoid contents (5.94 ± 0.04 mg/g, Quercetin Equivalents) and Fe2+-chelation (52%) potential with DPPH radicals-quenching IC50 at 1.35 ± 0.16 mg/mL, while the aqueous ethanolic extract exhibited maximum phenolics contents (136.08 ± 0.12 mg/g, gallic acid equivalents) with DPPH scavenging potential at IC50 0.615 ± 0.06 mg/mL. Aqueous ethanolic extract and standard quercetin DPPH radicals scavenging's were equal potent at 10 mg/mL concentrations. The aqueous ethanolic extract showed highest analgesic effect with pain reduction rates 89.86% (p = 0.03), 87.50% (p < 0.01), and 99.66% (p = 0.0004) after 60, 90, and 120 min, respectively. Additionally, aqueous ethanolic extract exhibited the highest anti-inflammation capacity at 41.07% (p < 0.0001), 34.51% (p < 0.0001), and 24.82% (p < 0.0001) after 2, 3, and 6 h of extract's administration, respectively. The phytochemical constituents, significant anti-oxidant potential, remarkable analgesic, and anti-inflammatory bioactivities of extracts supported the traditionally claimed anti-inflammatory and analgesic plant activities.

Gold Nanoparticles and Graphene Oxide Flakes Synergistic Partaking in Cytosolic Bactericidal Augmentation: Role of ROS and NOX2 Activity.

Gold nanoparticles (GNPs) and graphene oxide flakes (GOFs) exerted significantly (p < 0.0001) supportive roles on the phagocytosis bioactivity of the immune cells of phagocytic nature against the Gram-positive and Gram-negative human pathogenic bacteria Staphylococcus aureus and Escherichia coli. Under experimental conditions, upon bacterial exposure, the combined GNPs and GOFs induced significant clearance of bacteria through phagosome maturation (p < 0.0001) from time-points of 6 to 30 min and production of reactive oxygen species (ROS, p < 0.0001) through the NADPH oxidase 2 (NOX2, p < 0.0001)-based feedback mechanism. The effects of the combined presence of GNPs and GOFs on phagocytosis (p < 0.0001) suggested a synergistic action underway, also achieved through elevated signal transduction activity in the bone-marrow-derived macrophages (BMDM, p < 0.0001). The current study demonstrated that GNPs' and GOFs' bactericidal assisting potentials could be considered an effective and alternative strategy for treating infections from both positive and negative bacterial strains.

Anti-Microbial, Anti-Oxidant, and α-Amylase Inhibitory Activity of Traditionally-Used Medicinal Herbs: A Comparative Analyses of Pharmacology, and Phytoconstituents of Regional Halophytic Plants' Diaspora.

Halophytes are the category of plants growing under harsh conditions of super-salinity, and are wide-spread in the coastal Mediterranean climatic conditions and desert oasis. They are adept at surviving through maintaining excessive production of enzymatic, and non-enzymatic secondary metabolites, especially phenolics and flavonoids that primarily work as anti-oxidants and phytoalexins. Five major halophyte species growing in the kingdom's Qassim's high-salted desert regions were investigated for confirming their traditionally used biological activity of sugar-control and anti-infectious properties. In this context, the comparative presence of phenolics, and flavonoids together with anti-microbial, anti-oxidants, and the anti-diabetic potentials of the plants' extracts were investigated through the α-amylase inhibition method. The highest concentrations of phenolics and flavonoids were detected in Salsola imbricata (360 mg/g of the extract as Gallic-Acid-Equivalents/GAE, and 70.5 mg/g of the extract as Rutin-Equivalents/RE). In contrast, the lowest concentrations of phenolics and flavonoids were detected in Salsola cyclophylla (126.6 mg/g GAE, and 20.5 mg/g RE). The halophytes were found rich in trace elements, a factor for water-retention in high-salinity plants, wherein iron and zinc elements were found comparatively in higher concentrations in Aeluropus lagopoides (4113 µg/kg, and 40.1 µg/kg, respectively), while the copper was detected in higher concentration (11.1 µg/kg) in S. imbricata, analyzed through Inductively Coupled Plasma Optical Emission Spectrometric (ICP-OES) analysis. The anti-oxidant potentials and α-amylase enzyme inhibition-based anti-diabetic activity of S. imbricata was significantly higher than the other halophytes under study, wherein S. cyclophylla exhibited the lowest level of α-amylase inhibition. The maximum DPPH radicals' (52.47 mg/mL), and α-amylase inhibitions (IC50 22.98 µg/mL) were detected in A.lagopoides. The anti-microbial activity against the Methicillin-Resistant Staphylococcus aureus was strongly exhibited by Zygophyllum simplex (33 mm Inhibition Zone-Diameter, 50 µg/mL Minimum-Inhibitory-Concentration), while Escherichia coli, Enterococcus faecalis, and Candida albicans growths were moderately inhibited by Tamarix aphylla. The current findings exhibited significant differences among the locally distributed halophytic plants species with regards to their bioactivity levels, anti-oxidant potentials, and the presence of trace elements. The ongoing data corroborated the plants' traditional uses in infections and diabetic conditions. The enhanced local distribution of the plants' diaspora and higher density of occurrence of these plants species in this region, in comparison to their normal climatic condition's counterparts, seemed to be affected by humans' use of the species as part of the traditional and alternative medicine over a period of long time.