Surface Modification of Nanoparticles Enhances Drug Delivery to the Brain and Improves Survival in a Glioblastoma Multiforme Murine Model.

Glioblastoma multiforme (GBM) is the most malignant type of brain tumor and has an extremely poor prognosis. Current treatment protocols lack favorable outcomes, and alternative treatments with superior efficacy are needed. In this study, we demonstrate that loading paclitaxel (PTX) in a polymeric, nanoparticulate delivery system is capable of improving its brain accumulation and therapeutic activity. We independently incorporated two different positively charged surface modifiers, poly(amidoamine) (PAMAM) and poly(ethylenimine) (PEI), onto poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG), PLGA-PEG, nanoparticles (NPs) using a modified nanoprecipitation technique that assures the formation of nanosized particles while exposing the positively charged polymer on the surface. The prepared NPs underwent comprehensive analyses of their size, charge, in vitro permeability against a BBB cell line, and in vivo biodistribution. Our results demonstrated the successful fabrication of positively charged NPs using PAMAM or PEI. Importantly, significant improvement in brain accumulation (in vivo) was associated with NPs containing PAMAM compared to unmodified NPs or NPs containing PEI. Finally, the efficacy of PAMAM-modified NPs loaded with PTX was evaluated with orthotopic human GBM xenografts in a mouse model, and the data demonstrated improved survival and equivalent safety compared to soluble PTX. Our data substantiate the importance of surface chemistry on the magnitude of NP accumulation in the brain and pave the way for further in vivo evaluation of chemotherapeutic drugs against GBM that have previously been overlooked because of their limited ability to cross the BBB.

Protective mechanism of turmeric (Curcuma longa) on carbofuran-induced hematological and hepatic toxicities in a rat model.

CONTEXT: Turmeric (Curcuma longa L. [Zingiberaceae]) is used in the treatment of a variety of conditions including pesticide-induced toxicity. OBJECTIVE: The study reports the antioxidant properties and the protective effects of turmeric against carbofuran (CF)-induced toxicity in rats. MATERIALS AND METHODS: The antioxidant potential was determined by using free radicals scavenging activity and ferric reducing antioxidant power values. Male Wistar rats were randomly divided into four groups, designated as control, turmeric (100 mg/kg/day), CF (1 mg/kg/day) and turmeric (100 mg/kg/day) + CF (1 mg/kg/day) treatments. All of the doses were administered orally for 28 consecutive days. The biological activity of the turmeric and CF was determined by using several standard biochemical methods. RESULTS: Turmeric contains high concentrations of polyphenols (8.97 ± 0.15 g GAEs), flavonoids (5.46 ± 0.29 g CEs), ascorbic acid (0.06 ± 0.00 mg AEs) and FRAP value (1972.66 ± 104.78 µM Fe2+) per 100 g of sample. Oral administration of CF caused significant changes in some of the blood indices, such as, mean corpuscular volume, corpuscular hemoglobin, white blood cell, platelet distribution width and induced severe hepatic injuries associated with oxidative stress, as observed by the significantly higher lipid peroxidation (LPO) levels when compared to control, while the activities of cellular antioxidant enzymes (including superoxide dismutase and glutathione peroxidase) were significantly suppressed in the liver tissue. DISCUSSION AND CONCLUSION: Turmeric supplementation could protect against CF-induced hematological perturbations and hepatic injuries in rats, plausibly by the up-regulation of antioxidant enzymes and inhibition of LPO to confer the protective effect.

Chemical proteomics to study metabolism, a reductionist approach applied at the systems level.

Cellular metabolism encompasses a complex array of interconnected biochemical pathways that are required for cellular homeostasis. When dysregulated, metabolism underlies multiple human pathologies. At the heart of metabolic networks are enzymes that have been historically studied through a reductionist lens, and more recently, using high throughput approaches including genomics and proteomics. Merging these two divergent viewpoints are chemical proteomic technologies, including activity-based protein profiling, which combines chemical probes specific to distinct enzyme families or amino acid residues with proteomic analysis. This enables the study of metabolism at the network level with the precision of powerful biochemical approaches. Herein, we provide a primer on how chemical proteomic technologies custom-built for studying metabolism have unearthed fundamental principles in metabolic control. In parallel, these technologies have leap-frogged drug discovery through identification of novel targets and drug specificity. Collectively, chemical proteomics technologies appear to do the impossible: uniting systematic analysis with a reductionist approach.

Comparative simulation of nonlinear radiative nano casson and maxwell fluids with periodic magnetic force and sensitivity analysis.

This study investigated cyclic magneto-hydrodynamic radiative effects in Casson and Maxwell fluids, including nonlinear radiation and Arrhenius activation energy. It promotes non-Newtonian fluid use in diverse fields like industry, manufacturing, sciences, medicine, and engineering. Using boundary layer approximations, non-dimensional equations are formulated. For numerical solutions, widely recognized explicit finite difference method (EFDM) has been utilized. To ensure the robustness of EFDM results, stability and convergence tests are performed. Exploration involve a detailed sensitivity analysis by using RSM, offering a thorough understanding of influential parameters. These analyses explore complex interactions among physical parameters, affecting Nusselt number, skin friction, and Sherwood number. Maxwell fluid's velocity is more affected by periodic magnetic force than Casson fluid, during the presence of nonlinear radiation. Additionally, nonlinear thermal radiation has a greater impact on temperature and concentration profiles compared to linear radiation for both fluids. Moreover, Casson fluid has a stronger influence on the average heat transfer rate compared to Maxwell fluid with nonlinear thermal radiation which is 8.6 % greater than the Maxwell fluid. On the other hand, at constant thermal radiation (Ra), due to decrease of Brownian motion (Nb), the rate of heat transfer is reduced by 1.2 % and 0.3 % respectively for Maxwell and Casson fluid. Also, for thermophoresis parameter (Nt), this rate is reduced by 2 % and 1.6 % respectively. The investigation also revealed that the Ra exhibits a positive sensitivity towards average Nusselt number, while Nb and Nt are displayed a negative sensitivity.

Numerical modeling of a MHD non-linear radiative Maxwell nano fluid with activation energy.

The present research explores linear as well as nonlinear radiation patterns based on the MHD non-Newtonian (Maxwell) nanofluid flow having Arrhenius activation energy. This study's core focus is MHD properties in non-Newtonian fluid dynamics and boundary layer phenomena analysis. It initiates with time-dependent equations, employing boundary layer approximations. Extensive numerical computations, executed with custom Compact Visual Fortran code and the EFD method, provide profound insights into non-Newtonian fluid behavior, revealing intricate force interactions and fluid patterns. To check the stability of the solution, a convergence and stability analysis is performed. With the values of ΔY = 0.25, Δτ = 0.0005, and ΔX = 0.20; it is found that the model convergence occurs to the Lewis number, Le > 0.016 as well as the Prandtl number, Pr > 0.08. In this context, investigating non-dimensional results that depend on multiple physical factors. Explanation and visual representations of the effects of different physical characteristics and their resultant temperatures, concentrations, and velocity profiles are provided. As a result of the illustrations, the skin friction coefficient and Sherwood number, which are calculated, as well as Nusselt values, have all come up in discussion. Additionally, detailed representations of isothermal lines and streamlines are implemented, and it is pointed out that the development of these features occurs at the same time as Brownian motion. Furthermore, the temperature field for Maxwell fluid is modified due to the impression of chemical reaction as well as the Dufour number (Kr and Du). Our research demonstrates the superior performance of non-Newtonian solutions, notably in cases involving activation energy and nonlinear radiation. This paradigm shift carries significant implications. In another context, the interplay between Maxwell fluid and nonlinear radiation is notably affected by activation energy, offering promising applications in fields like medicine and industry, particularly in groundbreaking cancer treatment approaches.

Mitoferrin-1 Promotes Proliferation and Abrogates Protein Oxidation via the Glutathione Pathway in Glioblastoma.

Median overall survival is very low in patients with glioblastoma (GBM), largely because these tumors become resistant to therapy. Recently, we found that a decrease in the cytosolic labile iron pool underlies the acquisition of radioresistance. Both cytosolic and mitochondrial iron are important for regulating ROS production, which largely facilitates tumor progression and response to therapy. Here, we investigated the role of the mitochondrial iron transporters mitoferrin-1 (MFRN1) and mitoferrin-2 (MFRN2) in GBM progression. Analysis of The Cancer Genome Atlas database revealed upregulation of MFRN1 mRNA and downregulation of MFRN2 mRNA in GBM tumor tissue compared with non-GBM tissue, yet only the tumor expression level of MFRN1 mRNA negatively correlated with overall survival in patients. Overexpression of MFRN1 in glioma cells significantly increased the level of mitochondrial iron, enhanced the proliferation rate and anchorage-independent growth of these cells, and significantly decreased mouse survival in an orthotopic model of glioma. Finally, MFRN1 overexpression stimulated the upregulation of glutathione, which protected glioma cells from 4-hydroxynonenal-induced protein damage. Overall, these results demonstrate a mechanistic link between MFRN1-mediated mitochondrial iron metabolism and GBM progression. Manipulation of MFRN1 may provide a new therapeutic strategy for improving clinical outcomes in patients with GBM.

Fabrications, Classifications, and Environmental Impact of PCM-Incorporated Textiles: Current State and Future Outlook.

Phase change materials (PCMs) are an extraordinary family of compounds that can store and release thermal energy during phase changes. In recent years, the incorporation of PCMs into textiles has attracted considerable interest, since it represents a unique way to improve the comfort and usefulness of textiles. This article examines the advancements achieved in the preparation, classifications, and environmental effects of PCM-integrated textiles, along with a roadmap for the future. Progress of different PCM has been reported including its pros and cons. In addition, fabrications of the PCM on the apparel have been highlighted. Moreover, this Review analyzed the positive environmental impact of PCM-integrated textiles including improved insulation, extended product lifespan, and energy savings along with negative effects like higher energy consumption in the manufacturing process, added chemical additives tending to have a negative impact on the environment, less disposal features textiles and many more with recent references. Moreover, the future outlook also reports more research on nanoencapsulation, making it energy efficient, ensuring affordability, and more applications in smart PCM textiles. It seeks to stimulate additional research, encourage innovation, and contribute to the creation of high-performance, energy-efficient textiles by investigating the possibilities of PCM-enhanced textiles. The future of PCM in textiles is hopeful, with continuous research and technological advances resolving the aforementioned difficulties.

The promise of targeting heme and mitochondrial respiration in normalizing tumor microenvironment and potentiating immunotherapy.

Cancer immunotherapy shows durable treatment responses and therapeutic benefits compared to other cancer treatment modalities, but many cancer patients display primary and acquired resistance to immunotherapeutics. Immunosuppressive tumor microenvironment (TME) is a major barrier to cancer immunotherapy. Notably, cancer cells depend on high mitochondrial bioenergetics accompanied with the supply of heme for their growth, proliferation, progression, and metastasis. This excessive mitochondrial respiration increases tumor cells oxygen consumption, which triggers hypoxia and irregular blood vessels formation in various regions of TME, resulting in an immunosuppressive TME, evasion of anti-tumor immunity, and resistance to immunotherapeutic agents. In this review, we discuss the role of heme, heme catabolism, and mitochondrial respiration on mediating immunosuppressive TME by promoting hypoxia, angiogenesis, and leaky tumor vasculature. Moreover, we discuss the therapeutic prospects of targeting heme and mitochondrial respiration in alleviating tumor hypoxia, normalizing tumor vasculature, and TME to restore anti-tumor immunity and resensitize cancer cells to immunotherapy.

COX4-1 promotes mitochondrial supercomplex assembly and limits reactive oxide species production in radioresistant GBM.

Glioblastoma (GBM) is a fatal disease with recurrences often associated with radioresistance. Although often effective at treating newly diagnosed GBM, increasing evidence suggests that radiotherapy-induced alterations in tumor metabolism promote GBM recurrence and aggressiveness. Using isogenic radiosensitive and radioresistant GBM cell lines and patient-derived xenolines, we found that acquired radioresistance is associated with a shift from a glycolytic metabolism to a more oxidative metabolism marked by a substantial increase in the activity of the mitochondrial respiratory chain complex cytochrome c oxidase (CcO). This elevated CcO activity was associated with a switch in the isoform expression of the CcO regulatory subunit COX4, from COX4-2 to COX4-1, assembly of CcO-containing mitochondrial supercomplexes (SCs), and reduced superoxide (O2 •-) production. Overexpression of COX4-1 in the radiosensitive cells was sufficient to promote the switch from glycolytic to oxidative metabolism and the incorporation of CcO into SCs, with a concomitant reduction in O2 •- production. Conversely, silencing of COX4-1 expression in normally radioresistant cells reduced CcO activity, promoted the disassembly of mitochondrial SCs, and increased O2 •- production. Additionally, gain or loss of COX4-1 expression was sufficient to induce the radioresistant or radiosensitive phenotype, respectively. Our results demonstrate that COX4-1 promotes SC assembly in GBM cells, and SC assembly may in turn regulate the production of reactive oxygen species and thus the acquisition of radioresistance in GBM.

Effect of Expression of Nuclear-Encoded Cytochrome C Oxidase Subunit 4 Isoforms on Metabolic Profiles of Glioma Cells.

Although often effective at treating newly diagnosed glioblastoma (GBM), increasing evidence suggests that chemo- and radiotherapy-induced alterations in tumor metabolism promote GBM recurrence and aggressiveness, as well as treatment resistance. Recent studies have demonstrated that alterations in glioma cell metabolism, induced by a switch in the isoform expression of cytochrome c oxidase subunit 4 (COX4), a key regulatory subunit of mammalian cytochrome c oxidase, could promote these effects. To understand how the two COX4 isoforms (COX4-1 and COX4-2) differentially affect glioma metabolism, glioma samples harvested from COX4-1- or COX4-2-overexpressing U251 cells were profiled using Gas chromatography-mass spectrometry GC-MS and Liquid Chromatography - Tandem Mass Spectrometry LC-MS/MS metabolomics platforms. The concentration of 362 metabolites differed significantly in the two cell types. The two most significantly upregulated pathways associated with COX4-1 overexpression were purine and glutathione metabolism; the two most significantly downregulated metabolic pathways associated with COX4-1 expression were glycolysis and fatty acid metabolism. Our study provides new insights into how Cytochrome c oxidase (CcO) regulatory subunits affect cellular metabolic networks in GBM and identifies potential targets that may be exploited for therapeutic benefit.

Mitoferrin, Cellular and Mitochondrial Iron Homeostasis.

Iron is essential for many cellular processes, but cellular iron homeostasis must be maintained to ensure the balance of cellular signaling processes and prevent disease. Iron transport in and out of the cell and cellular organelles is crucial in this regard. The transport of iron into the mitochondria is particularly important, as heme and the majority of iron-sulfur clusters are synthesized in this organelle. Iron is also required for the production of mitochondrial complexes that contain these iron-sulfur clusters and heme. As the principal iron importers in the mitochondria of human cells, the mitoferrins have emerged as critical regulators of cytosolic and mitochondrial iron homeostasis. Here, we review the discovery and structure of the mitoferrins, as well as the significance of these proteins in maintaining cytosolic and mitochondrial iron homeostasis for the prevention of cancer and many other diseases.

Cytochrome c oxidase mediates labile iron level and radioresistance in glioblastoma.

Radiotherapy is an important treatment modality for glioblastoma (GBM), yet the initial effectiveness of radiotherapy is eventually lost due to the development of adaptive radioresistance during fractionated radiation therapy. Defining the molecular mechanism(s) responsible for the adaptive radioresistance in GBM is necessary for the development of effective treatment options. The cellular labile iron pool (LIP) is very important for determining the cellular response to radiation, as it contributes to radiation-induced production of reactive oxygen species (ROS) such as lipid radicals through Fenton reactions. Recently, cytochrome c oxidase (CcO), a mitochondrial heme-containing enzyme also involved in regulating ROS production, was found to be involved in GBM chemoresistance. However, the role of LIP and CcO in GBM radioresistance is not known. Herein, we tested the hypothesis that CcO-mediated alterations in the level of labile iron contribute to adaptive radioresistance. Using an in vitro model of GBM adaptive radioresistance, we found an increase in CcO activity in radioresistant cells that associated with a decrease in the cellular LIP, decrease in lipid peroxidation, and a switch in the CcO subunit 4 (COX4) isoform expressed, from COX4-2 to COX4-1. Furthermore, knockdown of COX4-1 in radioresistant GBM cells decreased CcO activity and restored radiosensitivity, whereas overexpression of COX4-1 in radiosensitive cells increased CcO activity and rendered the cells radioresistant. Overexpression of COX4-1 in radiosensitive cells also significantly reduced the cellular LIP and lipid peroxidation. Pharmacological manipulation of the cellular labile iron level using iron chelators altered CcO activity and the radiation response. Overall, these results demonstrate a mechanistic link between CcO activity and LIP in GBM radioresistance and identify the CcO subunit isoform switch from COX4-2 to COX4-1 as a novel biochemical node for adaptive radioresistance of GBM. Manipulation of CcO and the LIP may restore the sensitivity to radiation in radioresistant GBM cells and thereby provide a strategy to improve therapeutic outcome in patients with GBM.

Thymoquinone in autoimmune diseases: Therapeutic potential and molecular mechanisms.

Autoimmune diseases (AUDs) are a multifactorial disease, among which rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis are more prevalent. Several anti-inflammatory, biologics, and AUD-modifying drugs are found effective against them, but their repeated use are associated with various adverse effects. In this review article, we have focused on the regulation of inflammatory molecules, molecular signaling pathways, immune cells, and epigenetics by natural product thymoquinone on AUDs. Studies indicate that thymoquinone can regulate inflammatory molecules including interferons, interleukins, tumor necrosis factor-α (TNF-α), oxidative stress, regulatory T cells, and various signaling pathways such as nuclear factor kappa beta (NF-κß), janus kinase/signal transduction and activator of transcription (JAK-STAT), mitogen-activated protein kinase (MAPK) at the molecular level and epigenetic alteration. As these molecules and signaling pathways with defective immune function play an important role in AUD development, controlling these molecules and deregulated molecular mechanism is a significant feature of AUD therapeutics. Interestingly thymoquinone is reported to possess all these potential. This article reviewed the deregulated mechanism of AUDs, and the action of thymoquinone on inflammatory molecules, immune cells, signaling pathways, and epigenetic machinery. Thymoquinone can be regarded as a potential drug candidate for AUD treatment.

Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma.

Glioblastoma remains the deadliest form of brain cancer, largely because these tumors become resistant to standard of care treatment with radiation and chemotherapy. Intracellular production of reactive oxygen species (ROS) is necessary for chemo- and radiotherapy-induced cytotoxicity. Here, we assessed whether antioxidant catalase (CAT) affects glioma cell sensitivity to temozolomide and radiation. Using The Cancer Genome Atlas database, we found that CAT mRNA expression is upregulated in glioma tumor tissue compared with non-tumor tissue, and the level of expression negatively correlates with the overall survival of patients with high-grade glioma. In U251 glioma cells, CAT overexpression substantially decreased the basal level of hydrogen peroxide, enhanced anchorage-independent cell growth, and facilitated resistance to the chemotherapeutic drug temozolomide and ionizing radiation. Importantly, pharmacological inhibition of CAT activity reduced the proliferation of glioma cells isolated from patient biopsy samples. Moreover, U251 cells overexpressing CAT formed neurospheres in neurobasal medium, whereas control cells did not, suggesting that the radio- and chemoresistance conferred by CAT may be due in part to the enrichment of glioma stem cell populations. Finally, CAT overexpression significantly decreased survival in an orthotopic mouse model of glioma. These results demonstrate that CAT regulates chemo- and radioresistance in human glioma.

Nutritional Composition and Bioactive Compounds in Tomatoes and Their Impact on Human Health and Disease: A Review.

Tomatoes are consumed worldwide as fresh vegetables because of their high contents of essential nutrients and antioxidant-rich phytochemicals. Tomatoes contain minerals, vitamins, proteins, essential amino acids (leucine, threonine, valine, histidine, lysine, arginine), monounsaturated fatty acids (linoleic and linolenic acids), carotenoids (lycopene and ß-carotenoids) and phytosterols (ß-sitosterol, campesterol and stigmasterol). Lycopene is the main dietary carotenoid in tomato and tomato-based food products and lycopene consumption by humans has been reported to protect against cancer, cardiovascular diseases, cognitive function and osteoporosis. Among the phenolic compounds present in tomato, quercetin, kaempferol, naringenin, caffeic acid and lutein are the most common. Many of these compounds have antioxidant activities and are effective in protecting the human body against various oxidative stress-related diseases. Dietary tomatoes increase the body's level of antioxidants, trapping reactive oxygen species and reducing oxidative damage to important biomolecules such as membrane lipids, enzymatic proteins and DNA, thereby ameliorating oxidative stress. We reviewed the nutritional and phytochemical compositions of tomatoes. In addition, the impacts of the constituents on human health, particularly in ameliorating some degenerative diseases, are also discussed.

Radioresistance in Glioblastoma and the Development of Radiosensitizers.

Ionizing radiation is a common and effective therapeutic option for the treatment of glioblastoma (GBM). Unfortunately, some GBMs are relatively radioresistant and patients have worse outcomes after radiation treatment. The mechanisms underlying intrinsic radioresistance in GBM has been rigorously investigated over the past several years, but the complex interaction of the cellular molecules and signaling pathways involved in radioresistance remains incompletely defined. A clinically effective radiosensitizer that overcomes radioresistance has yet to be identified. In this review, we discuss the current status of radiation treatment in GBM, including advances in imaging techniques that have facilitated more accurate diagnosis, and the identified mechanisms of GBM radioresistance. In addition, we provide a summary of the candidate GBM radiosensitizers being investigated, including an update of subjects enrolled in clinical trials. Overall, this review highlights the importance of understanding the mechanisms of GBM radioresistance to facilitate the development of effective radiosensitizers.

Antioxidant Potential, Subacute Toxicity, and Beneficiary Effects of Methanolic Extract of Pomelo (Citrus grandis L. Osbeck) in Long Evan Rats.

The aim of this study was to investigate the antioxidant potentials, subacute toxicity, and beneficiary effects of methanolic extract of pomelo (Citrus grandis L. Osbeck) in rats. Long Evans rats were divided into four groups of eight animals each. The rats were orally treated with three doses of pomelo (250, 500, and 1000 mg/kg) once daily for 21 days. Pomelo extract contained high concentrations of polyphenols, flavonoids, and ascorbic acid while exhibiting high 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power values. There was no significant change in the body weight, percentage water content, and relative organ weight at any administered doses. In addition, no significant alterations in the hematological parameters were also observed. However, rats which received 1000 mg/kg dose had a significant reduction in some serum parameters, including alanine transaminase (15.29%), alkaline phosphatase (2.5%), lactate dehydrogenase (15.5%), γ-glutamyltransferase (20%), creatinine (14.47%), urea (18.50%), uric acid (27.14%), total cholesterol (5.78%), triglyceride (21.44%), low-density lipoprotein cholesterol (40.74%), glucose (2.48%), and all atherogenic indices including cardiac risk ratio (24.30%), Castelli's risk index-2 (45.71%), atherogenic coefficient (42%), and atherogenic index of plasma (25%) compared to control. In addition, the highest dose (1000 mg/kg) caused a significant increase in iron (12.07%) and high-density lipoprotein cholesterol (8.87%) levels. Histopathological findings of the vital organs did not indicate any pathological changes indicating that pomelo is nontoxic, safe, and serves as an important source of natural antioxidants. In addition, the fruit extract has the potential to ameliorate hepato- and nephrotoxicities and cardiovascular diseases as well as iron deficiency anemia.

Ganoderma lucidum and Auricularia polytricha Mushrooms Protect against Carbofuran-Induced Toxicity in Rats.

The current study aimed to investigate the ameliorative effects of two types of mushrooms, Ganoderma lucidum (GL) and Auricularia polytricha (AP), against carbofuran- (CF) induced toxicity in rats. Male Wistar rats (n = 42) were divided into six equal groups. The rats in the negative control group received oral administration of CF at 1 mg/kg with the normal diet for 28 days. The treatment groups received oral administration of ethanolic extract of GL or AP at 100 mg/kg followed by coadministration of CF at 1 mg/kg with the normal diet for the same experimental period, respectively. In the CF alone treated group, there were significant decreases in the erythrocytic and thrombocytic indices but increases in the concentrations of the total leukocytes, including the agranulocytes. A significant increase in all of the liver function biomarkers except albumin, in lipid profiles except high-density lipoprotein, and in the kidney function markers occurred in the negative control group compared to the rats of the normal control and positive control groups. The coadministration of mushroom extracts significantly ameliorated the toxic effects of the CF. The GL mushroom extract was more efficacious than that of the AP mushroom, possibly due to the presence of high levels of phenolic compounds and other antioxidants in the GL mushroom.

Assessment of Toxicity and Beneficiary Effects of Garcinia pedunculata on the Hematological, Biochemical, and Histological Homeostasis in Rats.

This study was undertaken to investigate the toxicological profile of a methanolic extract of Garcinia pedunculata fruit in rats by conducting hematological, biochemical, and histopathological examinations. Long Evans rats were divided into four groups, each with 6 animals, and were treated with three oral doses (250, 500, and 1000 mg/kg) once daily for 21 days. The extract did not cause significant changes in body and relative organ weight, percent water content, or hematological parameters at any administered doses. However, a significant dose-dependent positive effect in serum lipid profile and all atherogenic indices including the cardiac risk ratio, Castelli's risk index-2, and the atherogenic coefficient were observed. Significant increases in the levels of iron and decreases in serum alkaline phosphatase, alanine transaminase, and lactate dehydrogenase activities and the levels of serum glucose were noted when the extract was administered at the highest dose (1000 mg/kg). Histopathological examination of the target tissues further confirmed that the extract was safe and had no observed toxicological features. Our study indicates that G. pedunculata fruit is nontoxic, has the potential to be effective against atherosclerosis, and may be used as a hepatoprotectant. The fruit extract is also beneficial to those with iron deficiency and hyperglycemia.

Beneficial roles of honey polyphenols against some human degenerative diseases: A review.

Honey contains many active constituents and antioxidants such as polyphenols. Polyphenols are phytochemicals, a generic term for the several thousand plant-based molecules with antioxidant properties. Many in vitro studies in human cell cultures as well as many animal studies confirm the protective effect of polyphenols on a number of diseases such as cardiovascular diseases (CVD), diabetes, cancer, neurodegenerative diseases, pulmonary diseases, liver diseases and so on. Nevertheless, it is challenging to identify the specific biological mechanism underlying individual polyphenols and to determine how polyphenols impact human health. To date, several studies have attempted to elucidate the molecular pathway for specific polyphenols acting against particular diseases. In this review, we report on the various polyphenols present in different types of honey according to their classification, source, and specific functions and discuss several of the honey polyphenols with the most therapeutic potential to exert an effect on the various pathologies of some major diseases including CVD, diabetes, cancer, and neurodegenerative diseases.