Investigating the Anti-inflammatory Effect of Quinoline Derivative: N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine Hydrochloride Loaded Soluble Starch Nanoparticles Against Methotrexate-induced Inflammation in Experimental Model.

BACKGROUND: It is necessary to develop advanced therapies utilizing natural ingredients with anti-inflammatory qualities in order to lessen the negative effects of chemotherapeutics. RESULTS: The bioactive N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine hydrochloride (NIQBD) was synthesized. After that, soluble starch nanoparticles (StNPs) was used as a carrier for the synthesized NIQBD with different concentrations (50 mg, 100 mg, and 200 mg). The obtained StNPs loaded with different concentrations of NIQBD were coded as StNPs-1, StNPs-2, and StNPs-3. It was observed that, StNPs-1, StNPs-2, and StNPs-3 exhibited an average size of 246, 300, and 328 nm, respectively. Additionally, they also formed with homogeneity particles as depicted from polydispersity index values (PDI). The PDI values of StNPs-1, StNPs-2, and StNPs-3 are 0.298, 0.177, and 0.262, respectively. In vivo investigation of the potential properties of the different concentrations of StNPs loaded with NIQBD against MTX-induced inflammation in the lung and liver showed a statistically substantial increase in levels of reduced glutathione (GSH) accompanied by a significant decrease in levels of oxidants such as malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein product (AOPP), matrix metalloproteinase 9/Gelatinase B (MMP-9), and levels of inflammatory mediators including interleukin 1-beta (IL-1ß), nuclear factor kappa-B (NF-κB) in both lung and liver tissues, and a significant decrease in levels of plasma homocysteine (Hcy) compared to the MTX-induced inflammation group. The highly significant results were obtained by treatment with a concentration of 200 mg/mL. Histopathological examination supported these results, where treatment showed minimal inflammatory infiltration and congestion in lung tissue, a mildly congested central vein, and mild activation of Kupffer cells in liver tissues. CONCLUSION: Combining the treatment of MTX with natural antioxidant supplements may help reducing the associated oxidation and inflammation.

Moringa oleifera leaves extract loaded gold nanoparticles offers a promising approach in protecting against experimental nephrotoxicity.

Cisplatin is one of the most important antitumor drugs, however; it has numerous adverse effects like nephrotoxicity which is considered one of cisplatin uses . The study was planned to evaluate the nephroprotective effect of M. oleifera leaves extract loaded gold nanoparticles (Au-NPs) against cisplatin-induced nephrotoxicity in rats. Initially, total phenolic contents (TPC) and the antioxidant activity of the M. oleifera leaves extract were evaluated and recorded 8.50 mg/g and 39.89 % respectively. After that, the dry leaves of M. oleifera were grinded into fine powder and extracted using water extraction system. Then, different volumes (0.5, 1 and 2 mL) of M. Oleifera were blended with constant volume of Au-NPs (1 mL). Both Au-NPs and M. oleifera extract loaded Au-NPs were investigated using transmission electron microscope (TEM) that illustrated the deposition of M. Oleifera onto Au-NPs. The experimental study was performed on seventy male albino rats alienated into seven groups. Group I healthy rats, group II injected with one dose of cisplatin (CisPt), groups from III to VII treated groups received CisPt then received M. Oleifera leaves extract alone and /or Au-NPs with different ratios and concentrations. After the experiment' time, serum urea and creatinine, kidney injury molecule-1 (KIM-1), advanced oxidation protein products (AOPP), monocyte chemoattractant protein-1 (MCP-1), tumor necrotic factor-α (TNF-α), and interleukin-6 (IL-6) were evaluated as markers of renal nephrotoxicity. The kidneys of rats were excised for malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) assessments. Induction of CisPt showed a highly significant disturbance in oxidant/anti-oxidant balance and inducing inflammatory cascades supporting nephrotoxicity, while treatment with M. Oleifera leaves extract, Au-NPs, and the different concentrations of the extract loaded on Au-NPs had a crucial role in attenuating oxidative stress, enhancing antioxidant systems, and reducing inflammatory biomarkers, although the most significant results showed a powerful scavenging activity against nephrotoxicity induced by CisPt was obtained with M. Oleifera leaves extract loaded on Au-NPs with a concentration of 2:1 respectively.

Preparation of pumpkin oil-based nanoemulsion as a potential estrogen replacement therapy to alleviate neural-immune interactions in an experimental postmenopausal model.

As estrogen production decreases during menopause; the brain's metabolism tends to stall and become less effective. Estrogen most likely protects against neurodegeneration. Consequently, a comprehensive study of the benefits of hormone replacement therapy as a neuroprotective effect is urgently required. This study was designed to fabricate pumpkin seed oil nanoparticles (PSO) in nanoemulsion form (PSO-NE) and investigate their potential role in attenuating the neural-immune interactions in an experimental postmenopausal model.Sixty female white albino rats were divided into six groups: control, sham, ovariectomized (OVX), and three OVX groups treated with 17ß-estradiol, PSO, and PSO-NE respectively. Transmission Electron Microscopy (TEM), and particle size analyzer were performed for nanoemulsion evaluation. Serum levels of estrogen, brain amyloid precursor protein (APP), serum levels of nuclear factor kappa B (NF-κß), interleukin 6 (IL-6), transthyretin (TTR), and synaptophysin (SYP) were evaluated. The expression of estrogen receptors (ER-α, ß) in the brain tissue was estimated. The findings revealed that the approached PSO-NE system was able to reduce the interfacial tension, enhance the dispersion entropy, lower the system free energy to an extremely small value, and augment the interfacial area. PSO-NE, showed a significant increase in the levels of estrogen, brain APP, SYP, and TTR accompanied with a significant increased in the expression of brain ER-α, ß compared to the OVX group. In conclusion, the phytoestrogen content of PSO exhibited a significant prophylactic effect on neuro-inflammatory interactions, ameliorating both estrogen levels and the inflammatory cascades.

Dynamic expression of H19 and MALAT1 and their correlation with tumor progression biomarkers in a multistage hepatocarcinogenesis model.

Hepatocellular carcinoma (HCC) progresses sequentially in a stepwise pattern. Long noncoding RNA (lncRNA) can regulate the complex cascade of hepatocarcinogenesis. Our study aimed to elucidate the expression profile of H19 and MALAT1 during the different stages of hepatocarcinogenesis and the correlation between H19 and MALAT1 with the genes implicated in the carcinogenesis cascade. We employed a chemically induced hepatocarcinogenesis murine model to mimic the successive stages of human HCC development. Using real-time PCR, we analyzed the expression patterns of H19 and MALAT1, as well as the expression of biomarkers implicated in the Epithelial-Mesenchymal transition (EMT). The protein expression of the mesenchymal marker vimentin was also evaluated using immunohistochemistry in the stepwise induced stages. The histopathological evaluation of the liver tissue sections revealed significant changes during the experiment, with HCC developing at the final stage. Throughout the stages, there was a dynamic significant increase in the expression of H19 and MALAT1 compared to the normal control. Nevertheless, there was no significant difference between each stage and the preceding one. The tumor progression biomarkers (Matrix Metalloproteinases, vimentin, and ß-catenin) exhibited the same trend of steadily increasing levels. However, in the case of Zinc finger E-box-binding homeobox 1 and 2 (ZEB1 and ZEB2), the significant elevation was only detected at the last stage of induction. The correlation between lncRNAs and the tumor progression biomarkers revealed a strong positive correlation between the expression pattern of H19 and MALAT1 with Matrix Metalloproteinases 2 and 9 and vimentin. Our findings imply that genetic and epigenetic alterations influence HCC development in a stepwise progressive pattern.

Eicosapentaenoic acid loaded silica nanoemulsion attenuates hepatic inflammation through the enhancement of cell membrane components.

BACKGROUND: Liver inflammation is a multistep process that is linked with cell membrane fatty acids composition. The effectiveness of eicosapentaenoic acid (EPA) undergoes an irreversible change during processing due to their unsaturated nature; so the formation of nanocarrier for EPA is crucial for improving EPA's bioavailability and pharmacological properties. OBJECTIVE: In this study we aimed to evaluate the efficiency of EPA alone or loaded silica nanoemulsion on the management of hepatic inflammation induced by diethyl nitrosamine (DEN) through the enhancement of the cell membrane structure and functions. METHODS: The new formula of EPA was prepared to modify the properties of EPA. Forty-eight male Wistar albino rats were classified into: control, EPA, EPA loaded silica nanoemulsion (EPA-NE), DEN induced hepatic inflammation; DEN induced hepatic inflammation treated with EPA or EPA -NE groups. Plasma tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), liver hydroxyproline (Hyp) content, and liver oxidant and anti-oxidants were estimated. Urinary 8- hydroxyguanozine (8- OHdG) and erythrocyte membrane fatty acids fractions were estimated by High-performance liquid chromatography (HPLC). Also, histopathology studies were done to verify our hypothesis. RESULTS: It was appeared that administration of EPA, in particular EPA loaded silica nanoemulsion, ameliorated the inflammatory response, increased the activity of the anti-oxidants, reduced levels of oxidants, and improved cell membrane structure compared to hepatic inflammation induced by DEN group. Histopathological examination confirmed these results. CONCLUSION: EPA and notably EPA loaded silica nanoemulsion strongly recommended as a promising supplement in the management of hepatic inflammation.

Stimulatory effect of docosahexaenoic acid alone or loaded in zinc oxide or silver nanoparticles on the expression of glucose transport pathway.

The role of glucose transporters (GLUTs) in diabetes mellitus has become more prominent as a possible therapeutic target. In the present study, we aimed to compare the effect of zinc oxide nanoparticles (ZnONPs), silver nanoparticles (AgNPs), and docosahexaenoic acid (DHA) alone or loaded in ZnONPs or AgNPs on insulin signaling pathway and GLUTs expression in diabetic rats. In the experimental part, rats were divided into seven groups; control, diabetic, and the other five groups were diabetic received different treatments. Fasting blood sugar (FBS), serum level of insulin, insulin resistance (IR), and serum level of phosphatidylinositol 3-kinase (PI3K) were evaluated. In addition, insulin expression in pancreatic islets was assessed by immunohistochemical analysis, and the expression of liver GLUTs 1, 2, and 4 and liver insulin receptor substrate-1 (IRS-1) was evaluated by real-time polymerase chain reactions (RT-PCR). The results of the current study showed that ZnONPs, AgNPs, and DHA alone or loaded in ZnONPs or AgNPs attenuated levels of FBS, insulin and decreased IR in diabetic rats through enhancing the expression of GLUTs as well as IRS-1 and PI3K. Furthermore, AgNPs loaded with DHA showed the most significance with high comparability to the control group. In conclusion, this study elucidated the role of GLUTs and IRS-1 in diabetes and introduced novel characteristics of ZnONPs, AgNPs, and DHA alone or loaded in ZnONPs or AgNPs as a therapeutic modality to activate GLUTs and IRS1, which may be beneficial for diabetic patients with IR.

Indole glucosinolates exhibit anti-inflammatory effects on Ehrlich ascites carcinoma cells through modulation of inflammatory markers and miRNAs.

BACKGROUND: Nuclear factor-κB (NF-κB) has been identified as the major link between inflammation and cancer. Natural agents that inhibit this pathway are essential in attenuating inflammation induced by cancer or chemotherapeutic drugs. High intake of Brassicaceae vegetables has been determined to modulate essential pathways related to chronic diseases. In this study, we investigated the anti-proliferative and anti-inflammatory effects of the indole glucosinolates; indole-3-carbinol (I3C) and its metabolite 3,3-diindolylmethane (DIM) on the inflammatory biomarkers and miRNAs controlling the NF-κB pathway. METHODS AND RESULTS: In our study, we inoculated Ehrlich ascites carcinoma (EAC) cells in female albino mice, which increased their packed cell volume and induced a significant increase in the levels of several cytokines and inflammatory biomarkers (NF-κB IL-6, IL-1b, TNF-α, and NO). A significant elevation in inflammatory-medicated miRNAs (miR-31 and miR-21) was also noted. Treatment with 5-fluorouracil (5-FU) significantly reduced packed cell volume and viable cell count. However, it was accompanied by a significant increase in the levels of inflammatory markers and expression of miR-31 and miR-21. Nevertheless, although treatment with indoles (I3C and DIM) significantly reduced the packed cell volume and viable cell count, their prominent effect was the marked reduction of all inflammatory biomarkers compared to both the EAC untreated group and the EAC group treated with 5-FU. Moreover, the anti-inflammatory effect of I3C or DIM was accompanied by a significant decrease in the expression of miR-31 and miR-21. CONCLUSION: Our findings have; therefore, revealed that I3C and DIM have strong anti-inflammatory effects, implying that their use as a co-treatment with chemotherapeutic drugs can effectively improve the anti-tumor effect of chemotherapeutic drugs.

Prophylactic effect of probiotics fortified with Aloe vera pulp nanoemulsion against ethanol-induced gastric ulcer.

The purpose of this study was designed to evaluate the protective effect of probiotics fortified with Aloe vera pulp nanoemulsion on ethanol-induced gastric ulcer (GU). Freshly harvested Aloe vera pulp nanoemulsion was prepared and subsequently inoculated with 2% of the activated yogurt starter culture of Streptococcus thermophilus and Lactobacillus delbreukii subsp. bulgaricus (1:1). Chemical composition and physicochemical characterization of yogurt and the Aloe vera pulp nanoemulsion were assessed. GU was induced by ethanol. Rats were randomly assigned into control, GU, and four prophylactic groups including probiotics fortified with Aloe vera pulp nanoemulsion in the percentage of 0%, 10%, 20%, and 30% respectively. Serum levels of paraoxynase (POX) and tissue levels of malondialdehyde (MDA), nitric oxide (NO), and catalase (CAT) activity were assessed. Serum levels of nuclear factor kappa B (NF-κB), interleukin-1beta (IL-1ß), matrix metalloproteinase-9 (MMP-9), ceramide, and homocysteine (Hcy) were evaluated. Results indicated that the Aloe vera pulp nanoemulsion was appeared in spherical nano form with droplets diameter around 330 nm. Ethanol induces GU to cause a significant increase in the levels of MDA, NO, NF-κB, IL-1ß, MMP-9, Hcy, and ceramide along with a significant decrease in POX and CAT activities compared to the control group (p < 0.05). Pretreatment with different concentrations of probiotics fortified with Aloe vera pulp nanoemulsion with, especially the 30% concentration, significantly reduce the oxidative stress and ameliorate the release of different inflammatory mediators suggesting it as a promising approach in the protection against GU via scavenging superoxide radicals and inhibiting the activation of the inflammatory signaling cascades.

The diagnostic efficacy of circulating miRNAs in monitoring the early development of colitis-induced colorectal cancer.

Early detection of colorectal cancer and monitoring the progress in colon carcinogenesis stages is essential to reduce mortality. Therefore, there is continuous search for noninvasive biomarkers with high stability and good sensitivity and specificity. miRNAs have attracted attention as promising biomarkers as they are stably expressed in circulation. The aim of our study is to evaluate the aberrant expression of circulating miRNAs during the stepwise progress of colitis-associated colon cancer. This was accomplished through assessing the expression levels of five miRNAs (miR-141, miR-15b, miR-17-3p, miR-21, and miR-29a) in serum and their corresponding tissue samples through the different cycles of colorectal carcinogenesis cascade using the azoxymethane/dextran sulfate sodium murine model. We also compared the diagnostic performance of these selected miRNAs with the conventional tumor biomarkers CEA and CA 19-9. The results of our study revealed that the expression levels of those miRNAs were dynamically changing in accordance with the tumor development state. Moreover, their aberrant expression in serum was statistically correlated with that in tissue. Our data also revealed that serum miR-15b, miR-21, and miR-29a showed the best performance in terms of diagnostic power. Our findings highlight the efficiency of these circulating miRNAs not only for early diagnostics purposes, but also for monitoring progress in the colorectal carcinogenesis process, and therefore encouraging integrating these noninvasive biomarkers into the clinical diagnostic settings beside the traditional diagnostic markers for accurate screening of the early progress of colon carcinogenesis.

Evaluation of urinary 8-hydroxy-2-deoxyguanosine level in experimental Alzheimer's disease: Impact of carvacrol nanoparticles.

The present study aimed to compare the effect of carvacrol essential oil and carvacrol nanoemulsion against experimental Alzheimer's (AD). Forty male albino rats were used and divided into four groups as follow: control, AlCl3 induced AD, carvacrol oil treated and carvacrol nanoemulsion treated groups. Brain nor-epinephrine, serotonin and dopamine were analyzed by high performance liquid chromatography (HPLC). Levels of brain Thiobarbituric acid-reactive substances (TBARS), Superoxide dismutase (SOD), reduced glutathione (GSH), cholinesterase, and advanced oxidation protein product (AOPP) were evaluated. Urinary 8-hydroxyguanosine (8-OHdG) level was evaluated by HPLC. Brain Cyclooxygenase 1 and 2 (COX 1and 2) were analyzed by immunohistochemistry. AD induced by AlCl3 in rats was depicted by the significant increase in the neurotransmitters levels which is accompanied with high degree of oxidative stress that was revealed in the elevated level of urinary 8-OHdG along with significant elevation in AOPP, TBARS, and cholinesterase levels and a significant decrease in SOD and GSH; these results are confirmed by immunohistochemistry analysis of COX 1 and 2. On the other hand, the treatment with carvacrol oil and carvacrol nanoemulsion were capable of mitigate effects mediated by AlCl3 administration in treated rats. While the treatment with both approached succeeded to retract the negative impact of AlCl3; but the effect of carvacrol nanoemulsion was more notable than the essential oil. Carvacrol oil and carvacrol nanoemulsion were eminent to overturn AlCl3 induced brain AD which could be imputed to antioxidant and anti-inflammatory capabilities of carvacrol to alter oxidative stress effect. In extension; carvacrol nanoemulsion were evident to give more effective and efficient way in carvacrol delivery to pass through blood brain barriers and ameliorate brain changes.

Immunomodulatory Effects of MSCs in Bone Healing.

Mesenchymal stem cells (MSCs) are capable of differentiating into multilineage cells, thus making them a significant prospect as a cell source for regenerative therapy; however, the differentiation capacity of MSCs into osteoblasts seems to not be the main mechanism responsible for the benefits associated with human mesenchymal stem cells hMSCs when used in cell therapy approaches. The process of bone fracture restoration starts with an instant inflammatory reaction, as the innate immune system responds with cytokines that enhance and activate many cell types, including MSCs, at the site of the injury. In this review, we address the influence of MSCs on the immune system in fracture repair and osteogenesis. This paradigm offers a means of distinguishing target bone diseases to be treated with MSC therapy to enhance bone repair by targeting the crosstalk between MSCs and the immune system.

Galunisertib downregulates mutant type I collagen expression and promotes MSCs osteogenesis in pediatric osteogenesis imperfecta.

Qualitative alterations in type I collagen due to pathogenic variants in the COL1A1 or COL1A2 genes, result in moderate and severe Osteogenesis Imperfecta (OI), a rare disease characterized by bone fragility. The TGF-ß signaling pathway is overactive in OI patients and certain OI mouse models, and inhibition of TGF-ß through anti-TGF-ß monoclonal antibody therapy in phase I clinical trials in OI adults is rendering encouraging results. However, the impact of TGF-ß inhibition on osteogenic differentiation of mesenchymal stem cells from OI patients (OI-MSCs) is unknown. The following study demonstrates that pediatric skeletal OI-MSCs have imbalanced osteogenesis favoring the osteogenic commitment. Galunisertib, a small molecule inhibitor (SMI) that targets the TGF-ß receptor I (TßRI), favored the final osteogenic maturation of OI-MSCs. Mechanistically, galunisertib downregulated type I collagen expression in OI-MSCs, with greater impact on mutant type I collagen, and concomitantly, modulated the expression of unfolded protein response (UPR) and autophagy markers. In vivo, galunisertib improved trabecular bone parameters only in female oim/oim mice. These results further suggest that type I collagen is a tunable target within the bone ECM that deserves investigation and that the SMI, galunisertib, is a promising new candidate for the anti-TGF-ß targeting for the treatment of OI.

Bombax ceiba Linn. leaf extract rich in phenolic compounds to mitigate non-alcoholic fatty liver-related complications in experimental model.

OBJECTIVES: Obesity, diabetes mellitus, insulin resistance (IR), and hypertriglyceridemia are common features observed in non-alcoholic fatty liver diseases (NAFLD). There is a critical medical necessity to find novel therapeutics that can halt the development of NAFLD. METHODS: Bombax ceiba Linn. leaf extract was prepared and its phytochemical profile was determined. Standard and high carbohydrate high-fat diets (HCHF) were prepared. Rats were fed HCHF for 18 weeks to induce a non-alcoholic fatty liver (NAFL) model. Forty male rats were divided into control, B. ceiba Linn. leaf extract, NAFL, prophylactic, and treated groups. Serum fasting blood sugar (FBS), insulin, insulin resistance (HOMA-IR), cholesterol, high-density lipoprotein (HDL), triglycerides (TG), low density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), intelectin-1 (ITLN1), p38 MAP kinase (MAPK), peroxisome proliferator-activated receptor alpha (PPAR-α), and interleukin-6 (IL-6) were evaluated. RESULTS: Data obtained showed that HCHF-induced NAFL resulting in a significant increase in FBS, serum insulin, HOMA-IR, cholesterol, LDL, TG, ALT, AST, and IL-6 and a significant decrease in serum levels of HDL, ITLN1, p38 MAP kinase, and PPAR-α compared to the control group. The analysis of B. ceiba Linn. leaf extract showed high content of phenol compounds which may cause a significant decrease in the levels of FBS, insulin, HOMA-IR values, lipid profile, and levels of IL-6 while a significant increase in serum levels of LDL, ITLN1, p38 MAP kinase, and PPAR-α compared to the NAFL group. CONCLUSIONS: B. ceiba Linn. Leaf extract is a highly protective and promising therapeutic agent against inflammation and oxidative stress in the NAFLD model induced by HCHF.

Niazimicin: A thiocarbamate glycoside from Moringa oleifera Lam. seeds with a novel neuroprotective activity.

Moringa oleifera (MO) known as the miracle tree is a famous nutritional source in many countries. In this study, the neuroprotective activity of MO seeds was investigated. Fractions of the 70% ethanol seed extract of MO were injected at a dose of 250 mg kg-1  day-1 to albino rats for 15 days, after-which induction of dementia was done using 100 mg/kg AlCl3 over 30 days. Results revealed that all fractions ameliorated the effects of AlCl3 where methylene chloride and ethyl acetate fractions, containing the major bioactive compound niazimicin (NZ), showed the best activities. Biological investigations proved NZ to be a highly potent neuroprotective drug lead as a first report, by causing a decrease in the levels of malondialdehyde, cholinesterase, nitric oxide (NO) and amyloid ß by 47%, 34%, 53% and 59%, respectively, and increasing glutathione levels by 54%. Molecular docking studies suggested NZ neuroprotective effects to be mediated by inhibition of caspase-3 and inducible nitric oxide synthase enzymes. PRACTICAL APPLICATIONS: The current findings present the neuroprotective effect of Moringa oleifera seeds consumed as a food supplement and in daily diet. In addition, niazimicin is a promising lead for the development of novel agents against Alzheimer's disease as seen by the reported results.

Potential neuroprotective activity of Mentha longifolia L. in aluminum chloride-induced rat model of Alzheimer's disease.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder manifested by cognitive deterioration where the available treatments failed to delay its progression. The objective of this study was to investigate the neuroprotective activity in an aluminum chloride (AlCl3 )-induced AD in vivo model and phytochemical profile of the traditional Egyptian herb Mentha longifolia (Ml). Male albino rats were injected with Ml fractions and essential oil for 15 days followed by AlCl3 for 30 days. Oxidative stress and neuroinflammatory markers were measured namely: malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), and nuclear factor-κB (NF-κB). Furthermore, cholinesterase activity was tested and analysis of brain neurotransmitters using HPLC was performed. Results showed that methylene chloride and ethyl acetate fractions were able to reverse the AlCl3 mediated MDA increase, GSH decrease and exhibited anticholinesterase activity. EaFr reversed the increased levels of NF-κB and NO. Ml fractions and oil counteracted the AlCl3 effect on brain neurotransmitters. Forty metabolites were tentatively characterized in the bioactive fractions using UPLC-PDA-ESI-MS. 5,6,4'-trihydroxy-3',7,8-trimethoxy flavone was isolated from Ml as a first report, in addition to 5,6-dihydroxy-3',4',7,8-tetramethoxy flavone and rosmarinic acid. These findings suggest that Ml is a promising nutraceutical and source of lead compounds halting AD progression. PRACTICAL APPLICATIONS: The results presented in this paper unravels the neuroprotective effect of Mentha longifolia fractions and oil by acting as anti-inflammatory, antioxidant agents, and regulating the levels of neurotransmitters. This provides basic knowledge for the development of Ml as a source of lead compounds and a promising food supplement protective against Alzheimer's disease.

Influence of irisin on diet-induced metabolic syndrome in experimental rat model.

OBJECTIVE: To evaluate the influence of irisin on the experimental paradigm of non-alcoholic fatty liver (NAFL) as a part of MetS cluster. METHODS: Forty male albino rats were divided into four groups; normal control, standard diet + irisin, high carbohydrate and fat diet (HCHF), and HCHF + irisin. After the experimental period, levels of fasting blood sugar (FBS), insulin, lipid profile, kidney functions, salusin-alpha (Sal-α), adropin, and retinol-binding protein-4 (RBP-4) were evaluated. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) expression in skeletal muscle was evaluated by quantitative real-time PCR. Aorta, liver, pancreas, and skeletal muscle tissue samples were prepared for histopathological examination. RESULTS: Rats administrated HCHF showed elevated levels of FBS, lipid profile, kidney functions, RBP-4, and downregulation of PGC-1α expression along with a decline in levels of insulin, Sal-α, and adropin while administration of irisin significantly attenuated these levels. CONCLUSIONS: Irisin as based therapy could emerge as a new line of treatment against MetS and its related diseases.

Effect of Ficus carica L. leaves extract loaded gold nanoparticles against cisplatin-induced acute kidney injury.

BACKGROUND: Cisplatin (CisPt) is one of the most widely used and highly effective drugs for the treatment of various solid tumors, unfortunately acute kidney injury (AKI) is considered one of its side effects through several mechanisms including production of reactive oxygen species (ROS), pro-inflammatory and pro-fibrotic cytokines. Due to the poor effect of AKI therapy, the use of nanoparticles loaded with natural extracts for delivering to the kidney molecules are desirable. AIM: This study aims to investigate the effectiveness of different concentrations of gold nanoparticles (Au-NPs) as a carrier for Ficus carica L. (Fig) leaves extract against CisPt induced AKI. METHODS: Seventy male albino rats were used and divided into seven groups. After the experimental period, blood was withdrawn, serum was separated for determination of urea, creatinine, homocystein (Hcy) and folic acid while reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC) and hydroxyproline content (Hyp) were evaluated in kidney tissue homogenate. RESULTS: CisPt induced AKI in rats and results in a significant increase in the levels of serum urea, creatinine, Hcy and kidney Hyp, lipid peroxidation along with a significant reduction of kidney GSH, NO and TAC compared to the control rats. Treatment with Au-NPs and Fig extract particularly in a ratio of (3:2) respectively was shown to improve renal functions with efficient capacity in scavenging ROS and reduced AKI severity. CONCLUSION: Au-NPs enhanced the anti-oxidative properties of the Fig extract in targeting kidney damaged tissue and reduced oxidative toxicity induced by CisPt.

Solvent-free and one-pot synthesis of silver and zinc oxide nanoparticles: Activity toward cell membrane component and insulin signaling pathway in experimental diabetes.

OBJECTIVE: To investigate and compare between the effect of both silver nanoparticles (AgNPs) and zinc oxide nanoparticles (ZnONPs) on insulin signaling pathway and insulin sensitivity in experimental diabetes. Preparation of AgNPs and ZnONPs in their solid state were carried out using pullulan (Natural polymer) as both reducing and stabilizing agent. The synthesis of these nanoparticles in a large scale were carried out without using any solvents. The experimental male albino rats received diluted solutions of AgNPs and ZNONPs. After the experimental period, blood was withdrawn; erythrocyte membrane lipids were extracted and fatty acids were determined by HPLC. Oxidant, antioxidant profile and phosphatidylinositol 3-kinase (PI3K) were estimated. RESULTS: It was observed that the as synthesized AgNPs and ZnONPs have nearly spherical shape with small size due to the stabilization effect of pullulan as proved by UV-vis spectroscopy (UV-vis), Transmission electron microscy (TEM) and Field emission scanning electron microscopy (FESEM), Zeta potential, Dynamic light scattering (DLS) and X-ray diffraction (XRD) techniques. The average hydrodynamic size of the formed AgNPs was 15 nm which is considered as very small size when compared with that of ZnONPs (above 50 nm). Fasting blood sugar was significantly increased in diabetic group along with elevation of MDA and DNA damage indicating the oxidative properties of streptozotocin. Whereas, the treatment with nanoparticles significantly attenuated these elevations. CONCLUSION: AgNPs and ZnONPs represent promising materials in attenuating diabetic complications and insulin resistance in experimental diabetes; no Impressive differences were observed between the effect of ZnONPs and AgNPs in this current research.

The therapeutic effect of nano-encapsulated and nano-emulsion forms of carvacrol on experimental liver fibrosis.

OBJECTIVE: The present study aimed to compare the therapeutic efficiency of nano-encapsulated and nano-emulsion carvacrol administration on liver injury in thioacetamide (TAA) treated rats. METHODS: To fulfill our target, we used sixty male albino rats classified into six groups as follow: control, nano-encapsulated carvacrol, nano-emulsion carvacrol, thioacetamide, treated nano-encapsulated carvacrol and treated nano-emulsion carvacrol groups. Blood samples were collected from all groups and the separated serum was used for analysis of the following biochemical parameters; aspartate aminotransferase (AST), alanine aminotransferase (ALT), S100 B protein, alpha fetoprotein (AFP) and caspase-3. The levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), monocyte chemoattractant protein-1(MCP-1) and hydroxyproline content were all evaluated in liver tissue homogenate. Histopathological examinations for liver tissues were also performed. RESULTS: Thioacetamide induced hepatic damage in rats as revealed by the significant increase in the levels of serum ALT, AST and produced oxidative stress as displayed by the significant elevation in the levels of hepatic MDA and NO concomitant with a significant decrease in GSH. In addition, thioacetamide significantly increased serum S100B protein, alpha fetoprotein and caspase-3 along with hepatic MCP-1 and hydroxyproline; these results were confirmed by the histopathological investigation. In contrast, nano-encapsulated and nano-emulsion carvacrol were able to ameliorate these negative changes in the thioacetamide injected rats. However, the effect of the nano-encapsulated form of carvacrol was more prominent than the nano-emulsion form. CONCLUSION: Nano-encapsulated and nano-emulsion carvacrol can ameliorate thioacetamide induced liver injury. These results could be attributed to the potential anti-inflammatory, antioxidant, and anti-apoptotic activities of carvacrol in addition to the effectiveness of the encapsulation technique that can protect carvacrol structure and increase its efficiency and stability. Moreover, nano-encapsulation of carvacrol is more efficient than nano-emulsion.

Effect of Au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations.

Dextran-capped gold nanoparticles (Au-dextran NPs) were prepared exploiting the natural polysaccharide polymer as both reducing and stabilizing agent in the synthesis process, aiming at studying their antitumor effect on solid carcinoma and EAC-bearing mice. To this end, Au-dextran NPs were designed via simple eco-friendly chemical reaction and they were characterized revealing the monodispersed particles with narrow distributed size of around 49nm with high negative charge. In vivo experiments were performed on mice. Biochemical analysis of liver and kidney functions and oxidation stress ratio in addition to histopathological investigations of such tumor tissues were done demonstrating the potentiality of Au-dextran NPs as antitumor agent. The obtained results revealed that EAC and solid tumors caused significant increase in liver and kidney functions, liver oxidant parameters, alpha feto protein levels and diminished liver antioxidant accompanied by positive expression of tumor protein p53 of liver while the treatment with Au-dextran NPs for both types caused improvement in liver and kidney functions, increased liver antioxidant, increased the expression level of B-cell lymphoma 2 gene and subsequently suppressed the apoptotic pathway. As a result, the obtained data provides significant antitumor effects of the Au-dextran NPs in both Ehrlich ascites and solid tumor in mice models.