Novel tetrahydroisoquinolines as DHFR and CDK2 inhibitors: synthesis, characterization, anticancer activity and antioxidant properties.

In this study, we synthesized new 5,6,7,8-tetrahydroisoquinolines and 6,7,8,9-tetrahydrothieno[2,3-c]isoquinolines based on 4-(N,N-dimethylamino)phenyl moiety as expected anticancer and/or antioxidant agents. The structure of all synthesized compounds were confirmed by spectral date (FT-IR, 1H NMR, 13C NMR) and elemental analysis. We evaluated the anticancer activity of these compounds toward two cell lines: A459 cell line (lung cancer cells) and MCF7 cell line (breast cancer cells). All tested compounds showed moderate to strong anti-cancer activity towards the two cell lines. Compound 7e exhibited the most potent cytotoxic activity against A549 cell line (IC50: 0.155 µM) while compound 8d showed the most potent one against MCF7 cell line (IC50: 0.170 µM) in comparison with doxorubicin. In addition, we examined the effect of compounds 7e and 8d regarding the growth of A549 and MCF7 cell lines, employing flow cytometry and Annexin V-FITC apoptotic assay. Our results showed that compound 7e caused cell cycle arrest at the G2/M phase with a 79-fold increase in apoptosis of A459 cell line. Moreover, compound 8d caused cell cycle arrest at the S phase with a 69-fold increase in apoptosis of MCF7 cell line. Furthermore, we studied the activity of these compounds as enzyme inhibitors against several enzymes. Our findings by docking and experimental studies that compound 7e is a potent CDK2 inhibitor with IC50 of 0.149 µM, compared to the Roscovitine control drug with IC50 of 0.380 µM. We also found that compound 8d is a significant DHFR inhibitor with an IC50 of 0.199 µM, compared to Methotrexate control drug with IC50 of 0.131 µM. Evaluation of the antioxidant properties of ten compounds was also studied in comparison with Vitamin C. Compounds 1, 3, 6, 7c and 8e have higher antioxidant activity than Vitamin C which mean that these compounds can used as potent antioxidant drugs.

Expression of concern: The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches.

Expression of concern for 'The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches' by Abeer H. Elmaidomy et al., RSC Adv., 2022, 12, 11769-11785, https://doi.org/10.1039/D2RA01340A.

Metabolomic Analysis and in Vitro Investigation of the Biological Properties of a By-Product Derived from Vicia faba.

By-products from plant sources are recently regarded as a valuable source of bioactive compounds. In this regard, the present study aims to assess the bioactivities of the 70 % MeOH extract obtained from Vicia faba peels and analyze its metabolomic profile. Acetylcholinesterase and carbohydrate metabolizing enzymes inhibitory activities of the plant extract were assayed using quantitative colorimetric tests. Antioxidant activity was estimated by DPPH assay, and cytotoxic activity was evaluated against normal fibroblast skin cells (1-BJ1). Ninety-one metabolites were tentatively identified using ultra-high-performance liquid chromatography (UHPLC) hyphenated with quadrupole-time-of-flight tandem mass spectrometry (QTOF-MS). Most of these compounds were described for the first time in the plant. In addition, catechin, rutin, quercitrin, and rhamnetin were isolated from the plant extract. The plant extract and the isolated compounds possessed no cytotoxic activity on (1-BJ1), while they exhibited anticholinesterase with the highest activity for 70 % MeOH extract (IC50 =120.11 mg/L), antioxidant potential with the highest activity for rutin (90.54±0.73 %), and carbohydrate metabolizing inhibitory activities with the highest activity for rutin. These discoveries imply that V. faba peels might serve as an efficient antioxidant, exhibit anticholinesterase properties, and have the potential for use in managing diabetes, all while avoiding cytotoxicity in normal cells.

Discovery of novel benzofuran-based derivatives as acetylcholinesterase inhibitors for the treatment of Alzheimer's disease: Design, synthesis, biological evaluation, molecular docking and 3D-QSAR investigation.

A series of novel benzofuran-based compounds 7a-s were designed, synthesized, and investigated in vitro as acetylcholinesterase inhibitors (AChEIs). Compounds 7c and 7e displayed promising inhibitory activity with IC50 values of 0.058 and 0.086 µM in comparison to donepezil with an IC50 value of 0.049 µM. The new molecules' antioxidant evaluation revealed that 7c, 7e, 7j, 7n, and 7q produced the strongest DPPH scavenging activity when compared to vitamin C. As it was the most promising AChEI, compound 7c was selected for further biological evaluation. Acute and chronic toxicity studies exhibited that 7c showed no signs of toxicity or adverse events, no significant differences in the blood profile, and an insignificant difference in hepatic enzymes, glucose, urea, creatinine, and albumin levels in the experimental rat group. Furthermore, 7c did not produce histopathological damage to normal liver, kidney, heart, and brain tissues, ameliorated tissue malonaldehyde (MDA) and glutathione (GSH) levels and reduced the expression levels of the APP and Tau genes in AD rats. Molecular docking results of compounds 7c and 7e showed good binding modes in the active site of the acetylcholinesterase enzyme, which are similar to the native ligand donepezil. 3D-QSAR analysis revealed the importance of the alkyl group in positions 2 and 3 of the phenyl moiety for the activity. Overall, these findings suggested that compound 7c could be deemed a promising candidate for the management of Alzheimer's disease.

Nutritional Composition and Anti-Type 2 Diabetes Mellitus Potential of Femur Bone Extracts from Bovine, Chicken, Sheep, and Goat: Phytochemical and In Vivo Studies.

Nutritional deficits in one's diet have been established as the key risk factor for T2DM in recent years. Nutritional therapy has been demonstrated to be useful in treating T2DM. The current study was carried out to assess the nutritional composition of bovine (12 months), chicken (4 months), sheep (13 months), and goat (9 months) femur bone extracts, as well as their potential therapeutic effects on T2DM regression in a Wistar albino rat model (500 mg/kg b.wt.). The proximate composition of the different extracts, their fatty acid composition, their amino acids, and their mineral contents were identified. In vivo data indicated considerably improved T2DM rats, as seen by lower serum levels of TL, TG, TC, ALT, AST, ALP, bilirubin, creatinine, urea, IL-6, TNF-α, sICAM-1, sVCAM-1, and MDA. Low levels of HDL-C, GSH, and total proteins were restored during this study. Histological investigations of liver and pancreatic tissue revealed that the distribution of collagen fibers was nearly normal. The bovine extract, on the other hand, was the most active, followed by the sheep, goat, and finally chicken extract. This research could result in the creation of a simple, noninvasive, low-cost, and reliable method for T2DM control, paving the way for potential early therapeutic applications in T2DM control.

D-Pinitol Content and Antioxidant and Antidiabetic Activities of Five Bougainvillea spectabilis Willd. Cultivars.

Diabetes mellitus is a major challenge for global health, and Bougainvillea spectabilis Willd. (B. spectabilis) is a widely used herbal remedy with diverse cultivars traditionally used for diabetes treatment. However, the comparative efficacy of these cultivars remains ambiguous. This study aimed to evaluate the D-pinitol content and DPPH radical-scavenging activity of methanolic leaves extracts of five B. spectabilis cultivars. Furthermore, the effects of these cultivars on various parameters, including blood glucose levels, oxidative stress markers, inflammatory cytokines, lipid profiles, liver enzymes, renal function markers, and histopathological changes, were assessed in STZ-induced diabetic rats after one month of oral daily treatment. All tested cultivars demonstrated significant improvements in the measured parameters, albeit to varying extents. Notably, the LOE cultivar, distinguished by its orange bracts, exhibited the highest efficacy, surpassing the effectiveness of glibenclamide, an antidiabetic medication, and displayed the highest concentration of D-pinitol. These findings underscore the importance of carefully selecting the appropriate B. spectabilis cultivar to maximize the antidiabetic efficacy, with a particular emphasis on the correlation between antidiabetic activity and D-pinitol concentrations.

Anti-Alzheimer activity of new coumarin-based derivatives targeting acetylcholinesterase inhibition.

New 2-oxo-chromene-7-oxymethylene acetohydrazide derivatives 4a-d were designed and synthesized with a variety of bioactive chemical fragments. The newly synthesized compounds were evaluated as acetylcholinesterase (AChE) inhibitors and antioxidant agents in comparison to donepezil and ascorbic acid, respectively. Compound 4c exhibited a promising inhibitory impact with an IC50 value of 0.802 µM and DPPH scavenging activity of 57.14 ± 2.77%. Furthermore, biochemical and haematological studies revealed that compound 4c had no effect on the blood profile, hepatic enzyme levels (AST, ALT, and ALP), or total urea in 4c-treated rats compared to the controls. Moreover, the histopathological studies of 4c-treated rats revealed the normal architecture of the hepatic lobules and renal parenchyma, as well as no histopathological damage in the examined hepatic, kidney, heart, and brain tissues. In addition, an in vivo study investigated the amelioration in the cognitive function of AD-rats treated with 4c through the T-maze and beam balance behavioural tests. Also, 4c detectably ameliorated MDA and GSH, reaching 90.64 and 27.17%, respectively, in comparison to the standard drug (90.64% and 35.03% for MDA and GSH, respectively). The molecular docking study exhibited a good fitting of compound 4c in the active site of the AChE enzyme and a promising safety profile. Compound 4c exhibited a promising anti-Alzheimer's disease efficiency compared to the standard drug donepezil.

Abelmoschus eculentus Seed Extract Exhibits In Vitro and In Vivo Anti-Alzheimer's Potential Supported by Metabolomic and Computational Investigation.

Abelmoschus esculentus Linn. (okra, F. Malvaceae) is a fruit widely consumed all over the world. In our study, the anti-Alzheimer's potential of A. esculentus was evaluated. An in vitro DPPH free radical assay on A. esculentus seed's total extract and AChE inhibition potential screening indicated a significant anti-Alzheimer's activity of the extract, which was confirmed through an in vivo study in an aluminum-intoxicated rat model. Additionally, in vivo results demonstrated significant improvement in Alzheimer's rats, which was confirmed by improving T-maze, beam balance tests, lower serum levels of AChE, norepinephrine, glycated end products, IL-6, and MDA. The levels of dopamine, BDNF, GSH, and TAC returned to normal values during the study. Moreover, histological investigations of brain tissue revealed that the destruction in collagen fiber nearly returns back to the normal pattern. Metabolomic analysis of the ethanolic extract of A. esculentus seeds via LC-HR-ESI-MS dereplicated ten compounds. A network pharmacology study displayed the relation between identified compounds and 136 genes, among which 84 genes related to Alzheimer's disorders, and focused on AChE, APP, BACE1, MAPT and TNF genes with interactions to all Alzheimer's disorders. Consequently, the results revealed in our study grant potential dietary elements for the management of Alzheimer's disorders.

Anti-Inflammatory and Antioxidant Properties of Malapterurus electricus Skin Fish Methanolic Extract in Arthritic Rats: Therapeutic and Protective Effects.

The protective and therapeutic anti-inflammatory and antioxidant potency of Malapterurus electricus (F. Malapteruridae) skin fish methanolic extract (FE) (300 mg/kg.b.wt/day for 7 days, orally) was tested in monosodium urate(MSU)-induced arthritic Wistar albino male rats' joints. Serum uric acid, TNF-α, IL-1ß, NF-𝜅B, MDA, GSH, catalase, SOD, and glutathione reductase levels were all measured. According to the findings, FE significantly reduced uric acid levels and ankle swelling in both protective and therapeutic groups. Furthermore, it has anti-inflammatory effects by downregulating inflammatory cytokines, primarily through decreased oxidative stress and increased antioxidant status. All the aforementioned lesions were significantly improved in protected and treated rats with FE, according to histopathological findings. iNOS immunostaining revealed that protected and treated arthritic rats with FE had weak positive immune-reactive cells. Phytochemical analysis revealed that FE was high in fatty and amino acids. The most abundant compounds were vaccenic (24.52%), 9-octadecenoic (11.66%), palmitic (34.66%), stearic acids (14.63%), glycine (0.813 mg/100 mg), and alanine (1.645 mg/100 mg). Extensive molecular modelling and dynamics simulation experiments revealed that compound 4 has the potential to target and inhibit COX isoforms with a higher affinity for COX-2. As a result, we contend that FE could be a promising protective and therapeutic option for arthritis, aiding in the prevention and progression of this chronic inflammatory disease.

The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches.

Tamarindus indica Linn. (Tamarind, F. Fabaceae) is one of the most widely consumed fruits in the world. A crude extract and different fractions of T. indica (using n-hexane, dichloromethane, ethyl acetate, and n-butanol) were evaluated in vitro with respect to their DPPH scavenging and AchE inhibition activities. The results showed that the dichloromethane and ethyl acetate fractions showed the highest antioxidant activities, with 84.78 and 86.96% DPPH scavenging at 0.10 µg mL-1. The n-hexane, dichloromethane, and ethyl acetate fractions inhibited AchE activity in a dose-dependent manner, and the n-hexane fraction showed the highest inhibition at 20 µg mL-1. The results were confirmed by using n-hexane, dichloromethane, and ethyl acetate fractions in vivo to regress the neurodegenerative features of Alzheimer's dementia in an aluminum-intoxicated rat model. Phytochemical investigations of those three fractions afforded two new diphenyl ether derivative compounds 1-2, along with five known ones (3-7). The structures of the isolated compounds were confirmed via 1D and 2D NMR and HRESIMS analyses. The isolated compounds were subjected to extensive in silico-based investigations to putatively highlight the most probable compounds responsible for the anti-Alzheimer activity of T. indica. Inverse docking studies followed by molecular dynamics simulation (MDS) and binding free energy (ΔG) investigations suggested that both compounds 1 and 2 could be promising AchE inhibitors. The results presented in this study may provide potential dietary supplements for the management of Alzheimer's disease.

Nitrophenyl-Group-Containing Heterocycles. I. Synthesis, Characterization, Crystal Structure, Anticancer Activity, and Antioxidant Properties of Some New 5,6,7,8-Tetrahydroisoquinolines Bearing 3(4)-Nitrophenyl Group.

Regioselective cyclocondensation of 2,4-diacetyl-5-hydroxy-5-methyl-3-(3-nitrophenyl/4-nitrophenyl)cyclohexanones 1a,b with cyanothioacetamide afforded the corresponding 7-acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8-(3- and -4-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2H)-thiones 2a,b. Reaction of compounds 2a,b with ethyl iodide, 2-chloroacetamide (4a), or its N-aryl derivatives 4b-e in the presence of sodium acetate trihydrate gave 3-ethylthio-5,6,7,8-tetrahydroisoquinoline 3 and (5,6,7,8-tetrahydroisoquinolin-3-ylthio)acetamides 5a-i, respectively. Cyclization of compounds 5b-d,f,g into their isomeric 1-amino-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxamides 6b-d,f,g was achieved by heating in ethanol containing a catalytic amount of sodium carbonate. Structures of all synthesized compounds were characterized on the basis of their elemental analyses and spectroscopic data. The crystal structure of 5,6,7,8-tetrahydroisoquinoline 5d was determined by X-ray diffraction analysis. In addition, the biological evaluation of some synthesized compounds as anticancer agents was performed, and only six compounds showed moderate to strong activity against PACA2 (pancreatic cancer cell line) and A549 (lung carcinoma cell line). Moreover, the antioxidant properties of most synthesized compounds were examined. The results revealed high antioxidant activity for the most tested compounds.

Quality Control, Anti-Hyperglycemic, and Anti-Inflammatory Assessment of Colvillea racemosa Leaves Using In Vitro, In Vivo Investigations and Its Correlation with the Phytoconstituents Identified via LC-QTOF-MS and MS/MS.

Colvillea racemosa is a cultivated ornamental plant that is a monotypic genus of Fabaceae. It is native to Madagascar, with limited studies. For the first time, the leaf quality control parameters, the anti-hyperglycemic and anti-inflammatory in vitro activity of Colvillea racemosa ethanol extract (CRE) and its fractions of petroleum ether (CRP), methylene chloride (CRMC), ethyl acetate (CREA), n-butanol (CRB), and methanol (CRME) were evaluated. It exhibited significant inhibition against α-amylase, α-glucosidase and membrane stabilization. CRB was the most active fraction, and in vivo studies revealed that oral treatment with CRB of STZ-induced diabetic rats efficiently lowered blood glucose by 67.78%, reduced serum nitric oxide and lipid peroxide levels by 41.23% and 38.45%, respectively, and increased the GSH level by 90.48%. In addition, compared with the diabetic group, there was a 52.2% decrease in serum VCAM, a 55.5% increase in paraoxonase, an improved lipid profile, and improved liver and kidney functions for a treated diabetic group with CRB. Metabolite profiling of CRB was determined by UPLC-ESI-QTOF-MS and tandem MS/MS. Twenty-three chromatographic peaks were identified, which were classified into phenolic compounds and amino acids. The characterized flavonoids were apigenin and luteolin derivatives.

Synthesis and hyperglycemic, biochemical and histopathological evaluation of novel sulfonylbiguanide and sulfonylurea derivatives as potent anti-diabetic agents.

New sulfonylbiguanide hydrochloride salts and sulfonylurea derivatives containing two sulfonyl groups were synthesized through the reaction of arylsulfonohydrazides with cyanoguanidine and p-tolylsulfonylisocyanate, respectively. Oral treatment of hyperglycemic rats with the synthesized sulfonylbiguanide derivatives 2 and sulfonylurea derivatives 3 revealed that sulfonylurea derivatives 3a and 3c possessed significant decrease of the elevated glucose in compression with the anti-diabetic standard drugs. Effects of the synthesized sulfonylurea derivatives 3a and 3c on the diabetic properties towards α-amylase, liver function enzyme levels (AST, ALT, ALP, TB and γ-GT), kidney functions (urea and creatinine), lipids profiles (TG, TL, TC and HDL-C) were studied. Also, the effect of sulfonylurea derivatives 3a and 3c as antioxidants (reduced glutathione and lipid peroxide) was evaluated. Histopathological examination of hepatic and pancreatic tissues was investigated. The obtained results suggested that the most potent sulfonylurea derivatives 3a and 3c might be possible used as novel diabetic inhibitor agents.

DNA damage and genetic aberration induced via different sized silver nanoparticles: Therapeutic approaches of Casimiroa edulis and Glycosmis pentaphylla leaves extracts.

Potential of Casimiroa edulis and Glycosmis pentaphylla leaves extracts were investigated against the effect of two different particle sizes of silver nanoparticles induced toxicity in mice. Mice received silver nanoparticles (AgNPs) (100 mg/kg) with 20 and 100 nm for four weeks followed by daily oral dose of extracts (500 mg/kg) for three weeks. C. edulis leaves identified fourteen phenolic compounds while, G. pentaphylla leaves identified, twelve phenolic compounds. Additionally, biochemical, genotoxicity, mutagenicity, and histopathological investigations were carried out, revealed that liver function activities, lipid profile, hydrogen peroxide, and C-reactive protein were significantly elevate post AgNPs exposure. While, superoxide dismutase, glutathione-S-transferases, and glutathione peroxidase significantly reduce. A marked amelioration in all detected biomarkers, improved histopathological changes and repair DNA damage after treated with C. edulis and G. pentaphylla leaves extracts. These extracts are used for the first time as promising candidate therapeutic agents against toxicity induced by AgNPs. PRACTICAL APPLICATIONS: The potential applications of AgNPs make it necessary to investigate the possible toxicity associated with release of free silver ions in the biological system. AgNPs of varying particle sizes had toxic effects as evidenced by alterations in some cellular biochemical parameters, genotoxicity, mutagenicity, and histopathological indices on mice. Casimiroa edulis and Glycosmis pentaphylla leaves extracts are used for the first time as promising candidate therapeutic, where they are able to ameliorate the toxicity induced via AgNPs and record vacillate percentage of improvement in the selected biomarkers, as a result of the bioactive secondary metabolites especially flavonoids and other polyphenolic compounds.

Anti-Inflammatory and Antioxidant Activities of Terpene- and Polyphenol-Rich Premna odorata Leaves on Alcohol-Inflamed Female Wistar Albino Rat Liver.

Premna odorata Blanco (Lamiaceae) is an ethnomedicinal plant native to different tropical regions. Although some reports addressed their anti-inflammatory, cytotoxic, and antituberculotic effects, their hepatoprotective potential is yet to be discovered. Accordingly, this study investigated the crude extract and different fractions of the plant leaves; metabolic profiling using liquid chromatography/high-resolution electrospray ionization mass spectroscopy (LC-HRESIMS) analysis, in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties for the dereplicated metabolite via online PreADMET program, ROS scavenger activity on the Hep G2 human liver cancer cell line, and the possible hepatic cellular treatment effects in alcohol-inflamed liver female Wistar albino rats. Metabolic profiling dereplicated a total of 28 metabolites from the crude extract and its various fractions. In silico ADMET and ROS scavenger activity screening suggested plant metabolites are of potential bioactivity. In vivo hepatic treatment with crude, defatted crude, and n-hexane leave extracts suggested all extracts significantly improved liver damage, which was indicated by the reduction of elevated serum levels of bilirubin, AST, ALT, ALP, CRP, TNF-α, ICAM-1, VCAM-1, and MDA. The reduced levels of GSH and TAC were normalized during the study. Histological examinations of liver tissue showed collagen fiber distribution nearly back to its normal pattern. The anti-inflammatory and antioxidant potentials of Premna odorata extracts could be partly related to the combined effects of these phytochemicals or their synergistic interactions.

The ameliorating effect of carotenoid rich fraction extracted from Dunaliella salina microalga against inflammation- associated cardiac dysfunction in obese rats.

The carotenoid rich fraction of microalgae Dunaliella salina (crf-DS) have been receiving great attention, due to they abilities to protect and improve various disorders. The objective of this study is to explore the therapeutic efficiency of crf-DS on obesity-assciated cardiac dysfunction in the high-fat diet (HFD) treated rats. These rats were orally administered with crf-DS (150 mg /kg body weight), for six consecutive weeks in comparison with reference drug(orlistat). Specific cardiac biomarkers were examined including; adiponectin, plasminogen activator inhibitor (PAI-1), glucagon, troponin-I (cTnI). The cell adhesion molecules (VCAM and ICAM), C-reactive protein (CRP), collagen type II (Col II), collagen alpha-1 (III) chain (Col3A1), lipoxygenase activity (LOX), as well as histopathological examination of cardiac tissue were investigated. Results indicated a significant reduction(P ≤ 0.05) in adiponectin and glucagon levels in serum of obese rats. However, cTnI, PAI-1, cell adhesion molecules, CRP, Col II, and Col3A1 and LOX levels declared marked increase. Histopathological examination of cardiac tissue showed fibrosis with severe congestion in the myocardial blood vessels. On the other hand, rats medicated with a crf-DS demonstrated noticeable ameliorating effect in all the measured parameters. Beside, myocardial tissue of obese rats showed no alteration. Hence, It could be concluded that, oral supplementation with crf-DS is able to attenuate cardiac dysfunction in obese rats. Further extended work is needed to exploit, the possible application of D. salina as nutraceuticals and food additives.

Toxicity assessment of the green Dunaliella salina microalgae.

The chronic toxicity of the Dunaliella salina microalgae was examined to evaluate its toxicity by the exposure of laboratory animals to high doses of Dunaliella salina and to estimate the possibility of using it as a safe supplement. Different hematological and biochemical analysis including complete blood picture (CBC), liver function enzyme activities; aminotransferases (ALT and AST), alkaline phosphatase (ALP), total bilirubin, kidney function tests; urea, creatinine, and albumin, as well as blood glucose level, were measured. The histopathological investigation was also carried out on hepatic, renal and cardiac architectures to examine its safety. Treatment with the dose 100 mg /kg body weight of D. salina powder daily for three consecutive months did not show any signs of toxicity in both genders and in mice and rats (no mortality, no hair loss, no diarrhea, no patches of yellow color appearance, etc…..). Moreover, abnormalities on behavior, food and water intakes and health status among the treated animals were not observed. CBC profile revealed a significant increase in hemoglobin (Hb) level in treating male and female mice and rats compared to their related control levels. The biochemical analysis clearly showed an insignificant change in liver enzyme activities, blood glucose level at a dose of 100 mg/kg. Also, an insignificant reduction in total urea and creatinine levels in both genders of mice and rats were noticed. Histopathological investigation showed normal architectures of all organs. Hence we can conclude that Dunaliella salina has been proven a safe profile up to 100 mg/kg body weight, however, it succeeded to stimulate the Hb synthesis compared to control groups, showing its benifits to be used safely as food additives or protective and curative agent in different diseases in future.

Synthesis, structural characterization and in vivo anti-diabetic evaluation of some new sulfonylurea derivatives in normal and silicate coated nanoparticle forms as anti-hyperglycemic agents.

Series of new sulfonylurea derivatives (gliclazide analogues) was synthesized and characterized. Thus, p-tolylsulfonylisocyanate was left to react with different amino derivatives under mild conditions to afford the desired sulfonylurea derivatives 1-5. The molecular structure of the compound N-(2,6-Dichlorophenylcarbamoyl)-4-methylbenzenesulfonamide, 1c has been elucidated by single crystal X-ray diffraction. Anti-diabetic properties of the synthesized compounds relative to anti-diabetic drug (gliclazidem MR60) were carried out, where most of the tested compounds showed significant activity for reducing the blood glucose level. The results revealed that compounds 1c and 5 showed better anti-diabetic activities compared with gliclazide. Activity of the most potent derivatives of sulfonylurea compounds namely 1c and 5 were increased using coated nanostructure tetraethyl orthosilicate (TEOS) as a modified release (MR) agent. The effect of the prepared sulfonylurea compounds against the diabetic condition was investigated using specific selected biomarkers as of liver enzyme activities as transaminases (AST, ALT) and alkaline phosphatase (ALP), lipids profiles; total cholesterol (TC), triacylglycerols (TG) and total lipid (TL). The antioxidants, oxidative stress biomarkers and histological examination were also examined and discussed.

Assessment of titanium dioxide nanoparticles toxicity via oral exposure in mice: effect of dose and particle size.

Objective: The aim of the present work is to evaluate the toxicity of titanium dioxide nanoparticles (TiO2NPs) according to their doses and particle sizes. Materials and methods: The effect of five days oral administration of TiO2NPs (21 and 80 nm) with different doses (50, 250 and 500 mg/kg body weight) was assessed in mice via measurement of oxidative stress markers; glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nitric oxide (NO), liver function indices; aspartate and alanine aminotransferases (AST and ALT), chromosomal aberrations and liver histopathological pattern. Results: The results revealed drastic alterations in all the measured parameters and showed positive correlation with the gradual dose increment. In addition, the smaller particle size of TiO2NPS (21 nm) had more adverse effect in all the selected biochemical parameters, genetic aberrations and histological investigations. Conclusions: Toxicity of TiO2NPs increases in a dose-dependent manner and vice versa with particles size. The evaluated biomarkers are good indicators for TiO2NPs toxicity. More detailed studies are required before the recommendation of TiO2NPS as food additives.

Cubic liquid crystalline nanoparticles containing a polysaccharide from Ulva fasciata with potent antihyperlipidaemic activity.

The present study involves the preparation of cubic liquid crystalline nanoparticles (cubsomes) for liver targeting to assess the potential of a formulated bioactive polysaccharide isolated from the hot aqueous extract of Ulva fasciata as an alternative natural agent with anti-hyperlipidaemic activity. Cubosomal nanoparticles were prepared by disrupting the cubic gel phase of the polysaccharide and water in the presence of a surfactant. Different lipid matrices and stabilizers were tested. All the formulations were in the nanosize range and showed sufficient negative charge to inhibit the aggregation of the cubosomes. Drug entrapment efficiencies (EEs%) were determined and in vitro release studies were performed. Transmission electron microscopy (TEM) and differential scanning calorimetry were used to analyze the loaded cubosomal nanoparticles containing glyceryl monostearate (GMO 2.25 g), poloxamer 407 (0.25 g) and 50 mg of the polysaccharide. A preclinical study comparing the cubic liquid crystalline nanoparticles containing polysaccharide to fluvastatin as a reference drug in hyperlipidaemic rats was conducted. The rats treated with the polysaccharide- loaded cubosomes showed significant decreases in total cholesterol (TC), triglycerides (TG) and total lipid (TL) compared to the untreated HL rats. In addition, oxidative stress and antioxidant biomarkers were measured in the HL rats. Compared to the untreated HL rats, the cubosome treated rats showed a significant reduction in malondialdehyde (MDA), whereas insignificant changes were detected in nitric oxide (NO), glutathione (GSH) levels and total antioxidant capacity (TAC). Further, vascular and intercellular adhesion molecules (VCAM, ICAM), and myeloperoxidase were demonstrated. A histopathological examination was conducted to study the alterations in histopathological lesions and to document the biochemical results. In conclusion, this study demonstrates the superiority of using a natural lipid regulator such as polysaccharide loaded cubosomes instead of fluvastatin.