Using biologically synthesized TiO2 nanoparticles as potential remedy against multiple drug resistant Staphylococcus aureus of bovine mastitis.

Presently, there is considerable emphasis on biological synthesis of nanoparticles containing bioactive reducing compounds with an aim to mitigate the harmful effects of pollutants. The approach under study is simple and ideal for the production of durable antimicrobial nanomaterials by novel single-step green synthesis of TiO2 metal oxide nanostructures using ginger and garlic crude aqueous extracts with bactericidal and catalytic activity. A variety of experimental techniques were used to characterize the synthesized nanomaterials. As demonstrated using x-ray diffraction and ultra-violet visible spectroscopy, the produced nanoparticles exhibited high absorption at 318 nm with size varying between 23.38 nm for ginger and 58.64 nm for garlic in biologically-reduced TiO2. At increasing concentrations (500, 1000 µg/50 µl), nanoparticles reduced with garlic exhibited enhanced bactericidal efficacy against multiple drug-resistant S. aureus and effectively decomposed toxic methylene blue (MB) dye. In conclusion, biologically-reduced TiO2 nanoparticles may prove an effective tool in the fight against microbial illnesses and drug resistance.

LC-MS/MS-Based Metabolomic Profiling of Constituents from Glochidion velutinum and Its Activity against Cancer Cell Lines.

This study aimed to establish the phytochemical profile of Glochidion velutinum and its cytotoxic activity against prostate cancer (PC-3) and breast cancer (MCF-7) cell lines. The phytochemical composition of G. velutinum leaf extract and its fractions was established with the help of total phenolic and flavonoid contents and LC-MS/MS-based metabolomics analysis. The crude methanolic extract and its fractions were studied for pharmacological activity against PC-3 and MCF-7 cell lines using the MTT assay. The total phenolic content of the crude extract and its fractions ranged from 44 to 859 µg GAE/mg of sample whereas total flavonoid contents ranged from 20 to 315 µg QE/mg of sample. A total of forty-eight compounds were tentatively dereplicated in the extract and its fractions. These phytochemicals included benzoic acid derivatives, flavans, flavones, O-methylated flavonoids, flavonoid O- and C-glycosides, pyranocoumarins, hydrolysable tannins, carbohydrate conjugates, fatty acids, coumarin glycosides, monoterpenoids, diterpenoids, and terpene glycosides. The crude extract (IC50 = 89 µg/mL), the chloroform fraction (IC50 = 27 µg/mL), and the water fraction (IC50 = 36 µg/mL) were found to be active against the PC-3 cell line. However, the crude extract (IC50 = 431 µg/mL), the chloroform fraction (IC50 = 222 µg/mL), and the ethyl acetate fraction (IC50 = 226 µg/mL) have shown prominent activity against breast cancer cells. Moreover, G. velutinum extract and its fractions presented negligible toxicity to normal macrophages at the maximum tested dose (600 µg/mL). Among the compounds identified through LC-MS/MS-based metabolomics analysis, epigallocatechin gallate, ellagic acid, isovitexin, and rutin were reported to have anticancer activity against both prostate and breast cancer cell lines and might be responsible for the cytotoxic activities of G. velutinum extract and its bioactive fractions.

6-Methoxyflavone and Donepezil Behavioral Plus Neurochemical Correlates in Reversing Chronic Ethanol and Withdrawal Induced Cognitive Impairment.

Purpose: Chronic ethanol exposure causes neurotoxicity and long-term learning and memory impairment along with hippocampal and frontal cortical dysfunction. Flavonoids possess antioxidant and anti-inflammatory properties believed to be contributory factors in reversing cognitive decline. 6-Methoxyflavone (6-MOF), a flavonoid occurring naturally in medicinal plants, has been reported to instigate neuroprotection by reversing cisplatin-induced hyperalgesia and allodynia. Consequently, this study was designed to investigate 6-MOF activity in models of chronic ethanol-induced cognitive impairment along with neurochemical correlates. Methods: Mice were given ethanol orally (2.0 g/kg daily) for 24 days plus either saline, 6-MOF (25-75mg/kg) or donepezil (4mg/kg) and then ethanol was withdrawn for the next 6 days. Animals were subsequently assessed for their cognitive performance in several models on days 1, 12, and 24, during abstinence (Day-26) and on the 7th day of the washout period. Following behavioral assessment, post-mortem dopamine, noradrenaline and vitamin C concentrations were quantified in the frontal cortex, hippocampus and striatum, using HPLC with UV detection. Results: Chronic ethanol treatment suppressed locomotor activity and impaired cognitive tasks, which included novel object recognition, performance in the Morris water maze as well as the Y-maze, socialization and nest-building behavior throughout the protocol and during withdrawal. These behavioral deficits were at least partially restored by the co-administration of 6-MOF or donepezil with ethanol as were ethanol-induced deficits in frontal cortical and hippocampal dopamine plus noradrenaline, together with striatal dopamine. 6-MOF co-administration with ethanol also modestly restored striatal vitamin C levels. Conclusion: It is postulated that, apart from donepezil, 6-MOF may be useful not only in the treatment of ethanol withdrawal severity but also in the management of chronic ethanol withdrawal induced cognitive impairment.

In-Vitro Catalytic and Antibacterial Potential of Green Synthesized CuO Nanoparticles against Prevalent Multiple Drug Resistant Bovine Mastitogen Staphylococcus aureus.

Nanoparticles prepared from bio-reduction agents are of keen interest to researchers around the globe due to their ability to mitigate the harmful effects of chemicals. In this regard, the present study aims to synthesize copper oxide nanoparticles (CuO NPs) by utilizing root extracts of ginger and garlic as reducing agents, followed by the characterization and evaluation of their antimicrobial properties against multiple drug resistant (MDR) S. aureus. In this study, UV-vis spectroscopy revealed a reduced degree of absorption with an increase in the extract amount present in CuO. The maximum absorbance for doped NPs was recorded around 250 nm accompanying redshift. X-ray diffraction analysis revealed the monoclinic crystal phase of the particles. The fabricated NPs exhibited spherical shapes with dense agglomeration when examined with FE-SEM and TEM. The crystallite size measured by using XRD was found to be within a range of 23.38-46.64 nm for ginger-doped CuO and 26-56 nm for garlic-doped CuO. Green synthesized NPs of ginger demonstrated higher bactericidal tendencies against MDR S. aureus. At minimum and maximum concentrations of ginger-doped CuO NPs, substantial inhibition areas for MDR S. aureus were (2.05-3.80 mm) and (3.15-5.65 mm), and they were measured as (1.1-3.55 mm) and (1.25-4.45 mm) for garlic-doped NPs. Conventionally available CuO and crude aqueous extract (CAE) of ginger and garlic roots reduced MB in 12, 21, and 38 min, respectively, in comparison with an efficient (100%) reduction of dye in 1 min and 15 s for ginger and garlic doped CuO NPs.

Synthesis and catalytic properties of calcium oxide obtained from organic ash over a titanium nanocatalyst for biodiesel production from dairy scum.

The fatty acid methyl ester (FAME) production from dairy effluent scum as a sustainable energy source using CaO obtained from organic ash over titanium dioxide nanoparticles (TNPs) as the transesterification nano-catalyst has been studied. The physical and chemical properties of the synthesized catalysts were characterized, and the effect of different experimental factors on the biodiesel yield was studied. It was revealed that the CaO-TiO2 nano-catalyst displayed bifunctional properties, has both basic and acid phases, and leads to various effects on the catalyst activity in the transesterification process. These bifunctional properties are critical for achieving simultaneous transesterification of dairy scum oil feedstock. According to the reaction results, the catalyst without and with a low ratio of TNPs showed a low catalytic activity. In contrast, the 3Ca-3Ti nano-catalyst had the highest catalytic activity and a strong potential for reusability, producing a maximum biodiesel yield of 97.2% for a 3 wt% catalyst, 1:20 oil to methanol molar ratio for the dairy scum, and a reaction temperature of 70 °C for a period of 120 min under a 300 kPa pressure. The physical properties of the produced biodiesel are within the EN14214 standards.

Melatonin as a Potential Regulator of Oxidative Stress, and Neuroinflammation: Mechanisms and Implications for the Management of Brain Injury-Induced Neurodegeneration.

This review covers the preclinical and clinical literature supporting the role of melatonin in the management of brain injury-induced oxidative stress, neuroinflammation, and neurodegeneration, and reviews the past and current therapeutic strategies. Traumatic brain injury (TBI) is a neurodegenerative condition, unpredictably and potentially progressing into chronic neurodegeneration, with permanent cognitive, neurologic, and motor dysfunction, having no standard therapies. Due to its complex and multi-faceted nature, the TBI has highly heterogeneous pathophysiology, characterized by the highest mortality and disability worldwide. Mounting evidence suggests that the TBI induces oxidative and nitrosative stress, which is involved in the progression of chronic and acute neurodegenerative diseases. Defenses against such conditions are mostly dependent on the usage of antioxidant compounds, the majority of whom are ingested as nutraceuticals or as dietary supplements. A large amount of literature is available regarding the efficacy of antioxidant compounds to counteract the TBI-associated damage in animal and cellular models of the TBI and several clinical studies. Collectively, the studies have suggested that TBI induces oxidative stress, by suppressing the endogenous antioxidant system, such as nuclear factor erythroid 2-related factor-2 (Nrf-2) increasing the lipid peroxidation and elevation of oxidative damage. Moreover, elevated oxidative stress may induce neuroinflammation by activating the microglial cells, releasing and activating the inflammatory cytokines and inflammatory mediators, and energy dyshomeostasis. Thus, melatonin has shown regulatory effects against the TBI-induced autophagic dysfunction, regulation of mitogen-activated protein kinases, such as ERK, activation of the NLRP-3 inflammasome, and release of the inflammatory cytokines. The collective findings strongly suggest that melatonin may regulate TBI-induced neurodegeneration, although further studies should be conducted to better facilitate future therapeutic windows.

Vegan, Vegetarian and Meat-Based Diets in Saudi Arabia.

Introduction One of the most essential risk factors for chronic medical conditions is dietary intake. The dietary habits in Saudi Arabia shifted towards the Western diet, which is high in fat, salt and sugar. Plant-based diets like vegetarianism and veganism have gained popularity in the last few years. Individuals commit to a plant-based diet for many reasons. Plant-based diets are associated with various health benefits but can still cause nutrition deficiencies.  Purpose The aim of the study is to examine the proportion of vegan, vegetarian and omnivore diets in Saudi Arabia. To compare between plant-eaters and meat-eaters in health, lifestyle factors and nutritional status. Methods A cross-sectional study was conducted. A previously validated online questionnaire was distributed via social media platforms. The authors used convenience sampling to collect the data. Results A total of 1018 respondents answered the survey. Most respondents 885 (87%) were omnivores, 52 were vegetarians (5%) and 81 (8%) were vegans. Moreover, 61% of the total respondents never consumed vitamin B12 supplements, and 10% consumed vitamin B12 daily. The majority of respondents 548 (54%) used no other dietary supplements, and 470 (46%) used unspecified dietary supplements. Vegan respondents were more likely than other diet categories to have healthier lifestyle features, including >3 times/week exercise (standardized residual = 3.55) and >7 hours of sleep (standardized residual = 2.44). Conclusion Majority of Saudis follow omnivore diets and the frequency of those who follow plant-based diets is very low. Those who follow a vegan diet seem to have better health rating and lifestyle compared to the omnivores. Public health officials and healthcare providers are encouraged to increase awareness among the Saudi population about the health benefits of a plant-based diet.

A Comprehensive Review on the Medicinal Importance; Biological and Therapeutic Efficacy of Lagenaria siceraria (Mol.) (Bottle Gourd) Standley Fruit.

Herbal remedies have been employed for the treatment and management of different diseases for ages. Herbal medicines are a promising choice over modern synthetic drugs because of their low side effects and are thus considered to be safe and effective in treating human diseases. Lagenaria siceraria (Mol.) Standley fruit (Bottle gourd) belongs to the Cucurbitaceae family that has been used in a different system of traditional medication to treat various diseases. This is a domestic plant that provides food as well as medication. This vegetable have low caloric values and high water contents. The edible portion of it contains phytochemicals like vitamins, proteins, choline, minerals, terpenoids, flavonoids, etc. Several bioactive compounds have been isolated from L. siceraria, including triterpenoids, sterols, cucurbitacins, flavones, C-glycosides and ß-glycosides. Researchers have evaluated various parts of this plant viz. fruit, root, flowers, and leaves for pharmacological activities like antianxiety, antidepressant, diuretic, antimicrobial, cytotoxic, antihyperlipidemic, cardio protective, analgesic, anti-inflammatory, anthelmintic, anti-hyperglycemic, antihepatotoxic, anti-urolithiatic, antistress, antiulcer, anticancer, hepatoprotective, anthelmintic, immunomodulatory, and antioxidant. In this review, an attempt has been made to explore its phytochemical constituents, traditional, medicinal, and pharmacological uses to highlight the therapeutic importance of this well-known plant. This would be helpful in reviving its importance and will highlight its several promising aspects to encourage researchers for further research on L. siceraria.

Enhancement of resistance by poultry manure and plant hormones (salicylic acid & citric acid) against tobacco mosaic virus.

Virus is the most menacing factor for plant, which causes enormous economic losses in agriculture worldwide. Tobacco mosaic virus is most hazardous virus among the plants that can spread through biological and non-biological sources. TMV is ancient virus that causes huge economic losses to pepper cucumber ornamental crops and tobacco. It can be controlled by reducing the population of vector through pesticide application. However, the rapid usage of synthetic chemicals causes environmental pollution and destroys our ecosystem. Consequently, different approaches just like natural derivatives should be adopted for the environmental friendly management for TMV. This in vitro study demonstrated the potential role of natural metabolites such as poultry manure and plant extracts such as salicylic acid and citric acid for the control of TMV. Two different concentrations of poultry manure 60G and 30G were used. Poultry manure was mixed with the soil at the time of sowing. Disease severity was minimum at maximum concentration as compared to the control. Meanwhile, two different concentrations of salicylic acid and citric acid 60% and 90% were applied by foliar sprayer after three-leaf stages. Disease severity was observed after 5, 10, 15, 20, 25, and 30 days after disease inoculation. Here also maximum concentration showed the minimum disease severity and higher concentration of both animal and plants extracts were used for following experiment. Quantitative real-time PCR (RT-qPCR) results demonstrated that different plant defense-related genes such as PR1a, PAL, PR5, NPR1, PRIb, and PDF1.2 were up-regulated. Furthermore, applications of each treatment-induced systemic resistance against a wide range of pathogen including TMV and fungal pathogen Botrytis cinerea.

Oral Administration of Gintonin Protects the Brains of Mice against Aß-Induced Alzheimer Disease Pathology: Antioxidant and Anti-Inflammatory Effects.

The study was aimed at analyzing the protective effects of gintonin in an amyloid beta- (Aß-) induced Alzheimer's disease (AD) mouse model. For the development of the Aß-induced AD mouse model, the amyloid-ß (Aß 1-42) peptide was stereotaxically injected into the brains of mice. Subsequently, gintonin was administered at a dose of 100 mg/kg/day/per oral (p.o) for four weeks daily, and its effects were evaluated by using western blotting, fluorescence analysis of brain sections, biochemical tests, and memory-related behavioral evaluations. To elucidate the effects of gintonin at the mechanistic level, the activation of endogenous antioxidant mechanisms, as well as the activation of astrocytes, microglia, and proinflammatory mediators such as nuclear factor erythroid 2-related factor 2 (NRF-2) and heme oxygenase-1 (HO-1), was evaluated. In addition, microglial cells (BV-2 cells) were used to analyze the effects of gintonin on microglial activation and signaling mechanisms. Collectively, the results suggested that gintonin reduced elevated oxidative stress by improving the expression of NRF-2 and HO-1 and thereby reducing the generation of reactive oxygen species (ROS) and lipid peroxidation (LPO). Moreover, gintonin significantly suppressed activated microglial cells and inflammatory mediators in the brains of Aß-injected mice. Our findings also indicated improved synaptic and memory functions in the brains of Aß-injected mice after treatment with gintonin. These results suggest that gintonin may be effective for relieving AD symptoms by regulating oxidative stress and inflammatory processes in a mouse model of AD. Collectively, the findings of this preclinical study highlight and endorse the potential, multitargeted protective effects of gintonin against AD-associated oxidative damage, neuroinflammation, cognitive impairment, and neurodegeneration.

Biogenesis of silver nanoparticles to treat cancer, diabetes, and microbial infections: a mechanistic overview.

Green synthesis of silver nanoparticles (SNPs) by harnessing the natural abilities of plant secondary metabolites has advantages over routine physical and chemical synthetic approaches due to their one-step experimental setup to reduce and stabilize the bulk silver into SNPs, biocompatible nature, and therapeutic significance. The unique size, shape, and biochemical functional corona of SNPs embellish them with the potential to perform therapeutic actions by adopting various mechanistic approaches including but not limited to the disruption of the electron transport chain, mitochondrial damage, DNA fragmentation, inhibition of ATP synthase activity, disorganization of the cell membrane, suspension of cellular signaling pathways, induction of apoptosis, and inhibition of enzymes activity. This review elaborates the biogenic synthesis of SNPs in redox chemical reactions by using plant secondary metabolites found in plant extracts. In addition, it explains the synergistic influence of physicochemical reaction parameters such as the temperature, pH, the concentration of the AgNO3, and the ratio of reactants to affect the reaction kinetics, molecular mechanics, enzymatic catalysis, and protein conformations that aid to affect the size, shape, and potential biochemical corona of nanoparticles. This review also provides up-to-date information on the mechanistic actions that embellish the plant-based SNPs, an anticancer, cytotoxic, antidiabetic, antimicrobial, and antioxidant potential. The mechanistic understanding of the therapeutic actions of SNPs will help in precision medicine to develop customized treatment and healthcare approaches for the welfare of the human population. KEY POINTS: • Significance of the biogenic nanoparticles • Biomedical application potential of the plant-based silver nanoparticles • Mechanism of the anticancer, antidiabetic, and antimicrobial actions of the plant-based silver nanoparticles.

Biomedical Potential of Plant-Based Selenium Nanoparticles: A Comprehensive Review on Therapeutic and Mechanistic Aspects.

Selenium nanoparticles (SeNPs) have advantages over other nanomaterials because of the promising role of selenium in the stabilization of the immune system and activation of the defense response. The use of SeNPs and their supplements not only have pharmacological significance but also boost and prepare the body's immune system to fight the pathogens. This review summarizes the recent progress in the biogenesis of plant-based SeNPs by using various plant species and the role of secondary metabolites on their biocompatible functioning. Phyto-synthesis of SeNPs results in the synthesis of nanomaterials of various, size, shape and biochemical nature and has advantages over other routine physical and chemical methods because of their biocompatibility, eco-friendly nature and in vivo actions. Unfortunately, the plant-based SeNPs failed to attain considerable attention in the pharmaceutical industry. However, a few studies were performed to explore the therapeutic potential of the SeNPs against various cancer cells, microbial pathogens, viral infections, hepatoprotective actions, diabetic management, and antioxidant approaches. Further, some of the selenium-based drug delivery systems are developed by engineering the SeNPs with the functional ligands to deliver drugs to the targeted sites. This review also provides up-to-date information on the mechanistic actions that the SeNPs adopt to achieve their designated tasks as it may help to develop precision medicine with customized treatment and healthcare for the ailing population.

Ongoing Research on the Role of Gintonin in the Management of Neurodegenerative Disorders.

Neurodegenerative disorders, namely Parkinson's disease (PD), Huntington's disease (HD), Alzheimer's disease (AD), and multiple sclerosis (MS), are increasingly major health concerns due to the increasingly aged population worldwide. These conditions often share the same underlying pathological mechanisms, including elevated oxidative stress, neuroinflammation, and the aggregation of proteins. Several studies have highlighted the potential to diminish the clinical outcomes of these disorders via the administration of herbal compounds, among which gintonin, a derivative of ginseng, has shown promising results. Gintonin is a noncarbohydrate/saponin that has been characterized as a lysophosphatidic acid receptor (LPA Receptor) ligand. Gintonin may cause a significant elevation in calcium levels [Ca2+]i intracellularly, which promotes calcium-mediated cellular effects via the modulation of ion channels and cell surface receptors, regulating the inflammatory effects. Years of research have suggested that gintonin has antioxidant and anti-inflammatory effects against different models of neurodegeneration, and these effects may be employed to tackle the neurological changes. Therefore, we collected the main scientific findings and comprehensively presented them, covering preparation, absorption, and receptor-mediated functions, including effects against Alzheimer's disease models, Parkinson's disease models, anxiety and depression-like models, and other neurological disorders, aiming to provide some insights for the possible usage of gintonin in the management of neurodegenerative conditions.

Oral Administration of Alpha Linoleic Acid Rescues Aß-Induced Glia-Mediated Neuroinflammation and Cognitive Dysfunction in C57BL/6N Mice.

In this work, we evaluated the effects of alpha linoleic acid (ALA), an omega-3 polyunsaturated fatty acid, on amyloid-beta-induced glial-cell-mediated neuroinflammation, amyloidogenesis, and cognitive dysfunction in mice. After an infusion of Aß1-42 (Aß1-42, 5 µL/5 min/mouse, intracerebroventricular injection (i.c.v), and respective treatments of ALA (60 mg/kg per oral for six weeks), neuroinflammation, apoptotic markers, and synaptic markers were evaluated by Western blot and immunofluorescence analyses. According to our findings, the infusion of Aß1-42 activated Toll-like receptor 4 (TLR4), glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the frontal cortices and hippocampi of the Aß1-42-injected mice to a greater extent than the Aß1-42 + ALA-cotreated mice. Similarly, there was an elevated expression of phospho-c-Jun-N-terminal kinase (p-JNK), phospho-nuclear factor-kB p65 (p-NF-kB p65 (Ser536)), and tissue necrosis factor (TNF) in the Aß1-42 infused mouse brains; interestingly, these markers were significantly reduced in the Aß + ALA-cotreated group. The elevated expression of pro-apoptotic markers was observed during apoptotic cell death in the Aß1-42-treated mouse brains, whereas these markers were markedly reduced in the Aß + ALA-cotreated group. Moreover, Aß1-42 infusion significantly increased amyloidogenesis, as assessed by the enhanced expression of the amyloid precursor proteins (APP) beta-amyloid cleaving enzyme-1 (BACE-1) and amyloid-beta (Aß1-42) in the mouse brains, whereas these proteins were markedly reduced in the Aß + ALA-cotreated group. We also checked the effects of ALA against Aß-triggered synaptic dysfunction and memory dysfunction, showing that ALA significantly improved memory and synaptic functions in Aß-treated mouse brains. These results indicated that ALA could be an applicable intervention in neuroinflammation, apoptotic cell loss, amyloidogenesis, and memory dysfunction via the inhibition of TLR4 and its downstream targets in Aß + ALA-cotreated mouse brains.

Dietary Supplementation of the Antioxidant Curcumin Halts Systemic LPS-Induced Neuroinflammation-Associated Neurodegeneration and Memory/Synaptic Impairment via the JNK/NF-κB/Akt Signaling Pathway in Adult Rats.

Curcumin is a natural polyphenolic compound widely known to have antioxidant, anti-inflammatory, and antiapoptotic properties. In the present study, we explored the neuroprotective effect of curcumin against lipopolysaccharide- (LPS-) induced reactive oxygen species- (ROS-) mediated neuroinflammation, neurodegeneration, and memory deficits in the adult rat hippocampus via regulation of the JNK/NF-κB/Akt signaling pathway. Adult rats were treated intraperitoneally with LPS at a dose of 250 µg/kg for 7 days and curcumin at a dose of 300 mg/kg for 14 days. After 14 days, the rats were sacrificed, and western blotting and ROS and lipid peroxidation assays were performed. For immunohistochemistry and confocal microscopy, the rats were perfused transcardially with 4% paraformaldehyde. In order to verify the JNK-dependent neuroprotective effect of curcumin and to confirm the in vivo results, HT-22 neuronal and BV2 microglial cells were exposed to LPS at a dose of 1 µg/ml, curcumin 100 µg/ml, and SP600125 (a specific JNK inhibitor) 20 µM. Our immunohistochemical, immunofluorescence, and biochemical results revealed that curcumin inhibited LPS-induced oxidative stress by reducing malondialdehyde and 2,7-dichlorofluorescein levels and ameliorating neuroinflammation and neuronal cell death via regulation of the JNK/NF-κB/Akt signaling pathway both in vivo (adult rat hippocampus) and in vitro (HT-22/BV2 cell lines). Moreover, curcumin markedly improved LPS-induced memory impairment in the Morris water maze and Y-maze tasks. Taken together, our results suggest that curcumin may be a potential preventive and therapeutic candidate for LPS-induced ROS-mediated neurotoxicity and memory deficits in an adult rat model.

Natural Dietary Supplementation of Curcumin Protects Mice Brains against Ethanol-Induced Oxidative Stress-Mediated Neurodegeneration and Memory Impairment via Nrf2/TLR4/RAGE Signaling.

The aim of the current study was to explore the underlying neuroprotective mechanisms of curcumin (50 mg/kg, for six weeks) against ethanol (5 mg/kg i.p., for six weeks) induced oxidative stress and inflammation-mediated cognitive dysfunction in mice. According to our findings, ethanol triggered reactive oxygen species (ROS), apoptosis, neuroinflammation, and memory impairment, which were significantly inhibited with the administration of curcumin, as assessed by ROS, lipid peroxidation (LPO), and Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/Heme-oxygenase-1) expression in the experimental mice brains. Moreover, curcumin regulated the expression of the glial cell markers in ethanol-treated mice brains, as analyzed by the relative expression TLR4 (Toll like Receptor 4), RAGE (Receptor for Advanced Glycations End products), GFAP (Glial fibrillary acidic protein), and Iba-1 (Ionized calcium binding adaptor molecule 1), through Western blot and confocal microscopic analysis. Moreover, our results showed that curcumin downregulated the expression of p-JNK (Phospo c-Jun N-Terminal Kinase), p-NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells), and its downstream targets, as assessed by Western blot and confocal microscopic analysis. Finally, the expression of synaptic proteins and the behavioral results also supported the hypothesis that curcumin may inhibit memory dysfunction and behavioral alterations associated with ethanol intoxication. Altogether, to the best of our knowledge, we believe that curcumin may serve as a potential, promising, and cheaply available neuroprotective compound against ethanol-associated neurodegenerative diseases.

Gintonin Mitigates MPTP-Induced Loss of Nigrostriatal Dopaminergic Neurons and Accumulation of α-Synuclein via the Nrf2/HO-1 Pathway.

Gintonin, a ginseng-derived glycolipoprotein isolated from ginseng, has been shown to be neuroprotective in several neurological disorders such as Alzheimer's disease models and depressive-like behaviors. In this study, we sought to investigate the potential protective mechanisms of gintonin in an in vivo MPTP and in vitro MPP+-mediated Parkinson's disease (PD) model. We hypothesized that activation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1, potential therapeutic targets for neurodegeneration) with gintonin could abrogate PD-associated neurotoxicity by modulating the accumulation of α-synuclein, neuroinflammation, and apoptotic cell death in an MPTP/MPP+ models of PD. Our in vivo and in vitro findings suggest that the neuroprotective effects of gintonin were associated with the regulation of the Nrf2/HO-1 pathway, which regulated the expression of proinflammatory cytokines and nitric oxide synthase and apoptotic markers in the substantia nigra and striatum of the mice. Moreover, the neuroprotective effects of gintonin were also associated with a reduction in α-synuclein accumulation in the mouse substantia nigra and striatum. The neuroprotective effects of gintonin were further validated by analyzing the effects of gintonin on MPP+-treated SH-SY5Y cells, which confirmed the protective effects of gintonin. It remains for future basic and clinical research to determine the potential use of gintonin in Parkinson's disease. However, to the best of our knowledge, marked alterations in biochemical and morphological setup of midbrain dopaminergic pathways by gintonin in MPTP mice model have not been previously reported. We believe that gintonin might be explored as an important therapeutic agent in the treatment of PD.

Report- Antioxidant, cytotoxicity, protein kinase inhibition and antibacterial activities of Fragaria x ananassa leaves.

Fragaria × ananassa leaves extracts prepared in different solvents were subject for antioxidative, cytotoxicity, protein kinase inhibition and antibacterial activities. The extracts showed varying activities depending upon solvent used for extraction. Combined effect of methanol and ethyl acetate showed maximum antioxidant and reducing power potential (207.65±6µg AAE/mg and 88.58±20µg AAE/mg, respectively). Maximum DPPH (2,2-diphenyl-1-picryl hydrazyl) free radical scavenging activity was calculated by when methanol: chloroform and acetate fractions were used (87.68% and 86.88% inhibition, respectively). Total phenolics varied from 186 to 1.91µg AAE/mg while total flavonoids also significantly varied among the extracts. The extracts also showed significant activities against brine shrimp larvae and bacterial strains tested. The study concludes that Fragaria × ananassa leaves can be a good source for isolation of active phytochemicals to be used in different industries.

Facile Synthesis of Highly Dispersed Co3O4 Nanoparticles on Expanded, Thin Black Phosphorus for a ppb-Level NO x Gas Sensor.

Expanded few-layer black phosphorus nanosheets (FL-BP NSs) were functionalized by branched polyethylenimine (PEI) using a simple noncovalent assembly to form air-stable overlayers (BP-PEI), and a Co3O4@BP-PEI composite was designed and synthesized using a hydrothermal method. The size of the highly dispersed Co3O4 nanoparticles (NPs) on the FL-BP NSs can be controlled. The BP-C5 (190 °C for 5 h) sensor, with 4-6 nm Co3O4 NPs on the FL-BP NSs, exhibited an ultrahigh sensitivity of 8.38 and a fast response of 0.67 s to 100 ppm of NO x at room temperature in air, which is 4 times faster than the response of the FL-BP NS sensor, and the lower detection limit reached 10 ppb. This study points to a promising method for tuning properties of BP-based composites by forming air-stable overlayers and highly dispersed metal oxide NPs for use in high-performance gas sensors.

Natural Dietary Supplementation of Anthocyanins via PI3K/Akt/Nrf2/HO-1 Pathways Mitigate Oxidative Stress, Neurodegeneration, and Memory Impairment in a Mouse Model of Alzheimer's Disease.

Well-established studies have shown an elevated level of reactive oxygen species (ROS) that induces oxidative stress in the Alzheimer's disease (AD) patient's brain and an animal model of AD. Herein, we investigated the underlying anti-oxidant neuroprotective mechanism of natural dietary supplementation of anthocyanins extracted from Korean black beans in the amyloid precursor protein/presenilin-1 (APP/PS1) mouse model of AD. Both in vivo (APP/PS1 mice) and in vitro (mouse hippocampal HT22 cells) results demonstrated that anthocyanins regulate the phosphorylated-phosphatidylinositol 3-kinase-Akt-glycogen synthase kinase 3 beta (p-PI3K/Akt/GSK3ß) pathways and consequently attenuate amyloid beta oligomer (AßO)-induced elevations in ROS level and oxidative stress via stimulating the master endogenous anti-oxidant system of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (Nrf2/HO-1) pathways and prevent apoptosis and neurodegeneration by suppressing the apoptotic and neurodegenerative markers such as activation of caspase-3 and PARP-1 expression as well as the TUNEL and Fluoro-Jade B-positive neuronal cells in the APP/PS1 mice. In vitro ApoTox-Glo™ Triplex assay results also showed that anthocyanins act as a potent anti-oxidant neuroprotective agent and reduce AßO-induced neurotoxicity in the HT22 cells via PI3K/Akt/Nrf2 signaling. Importantly, anthocyanins improve memory-related pre- and postsynaptic protein markers and memory functions in the APP/PS1 mice. In conclusion, our data suggested that consumption and supplementation of natural-derived anti-oxidant neuroprotective agent such as anthocyanins may be beneficial and suggest new dietary-supplement strategies for intervention in and prevention of progressive neurodegenerative diseases, such as AD.