Neuroprotective effect of biogenically synthesized ZnO nanoparticles against oxidative stress and ß-amyloid toxicity in transgenic Caenorhabditis elegans.

Amyloid ß (Aß) plaque accumulation-mediated neuronal toxicity has been suggested to cause synaptic damage and consequent degeneration of brain cells in Alzheimer's disease (AD). With the increasing prerequisite of eco-friendly nanoparticles (NPs), research investigators are utilizing green approaches for the synthesis of zinc oxide (ZnO) NPs for pharmaceutical applications. In this present study, ZnO NPs were synthesized from Acanthus ilicifolius to assess the neuroprotective properties in the AD model of transgenic Caenorhabditis elegans strains CL2006 and CL4176 expressing Aß aggregation. Our findings revealed that the therapeutic effect of green-synthesized ZnO NPs is associated with antioxidant activity. We also found that ZnO NPs significantly enhance the C. elegan's lifespan, locomotion, pharyngeal pumping, chemotaxis behavior also diminish the ROS deposition and intracellular productionMoreover, thioflavin T staining demonstrated that ZnO NPs substantially attenuated the Aß deposition in the C. elegans strain as compared to untreated worms. With their antioxidant properties, the greenly synthesized ZnO NPs had a significant neuroprotective efficiency on Aß-induced toxicity by reducing Aß aggregation and specifically reducing the progression of paralysis in the C. elegans AD model. Our findings suggested that the biosynthesized ZnO NPs could be thought-provoking candidates for age-associated neurodegenerative disorders accompanied by oxidative stress.

Isolongifolene-loaded chitosan nanoparticles synthesis and characterization for cancer treatment.

Recent breakthroughs in the field of nanoparticle-based therapeutic delivery methods have changed the standpoint of cancer therapy by effectively delaying the process of disease development. Nanoparticles have a unique capacity of good penetrating ability than other therapeutic leads used in traditional therapeutics, and also, they have the highest impact on disease management. In the current study isolongifolene-loaded Chitosan nanoparticles have been formulated, synthesized and then characterized by the use of Fourier Transform Infrared Spectroscopy, X-ray Diffraction, Scanning Electron Microscopy and Transmission Electron Microscopy. Further, the characterized chitosan nano formulation was evaluated for hemocompatibility, plasma stability, and in-vitro release. Isolongifolene-loaded chitosan nanoparticles were found to be compatible with plasma and also, they exhibited a constant release pattern. Hence, chitosan-loaded nanoparticles could be employed as an excellent adjuvant in cancer therapeutic, to combat the multi-drug resistance in solid tumors.

Progress in the development of naturally derived active metabolites-based drugs: Potential therapeutics for Alzheimer's disease.

Alzheimer's disease (AD) is an extensive age-associated neurodegenerative disorder. In spite of wide-ranging progress in understanding the AD pathology for the past 50 years, clinical trials based on the hypothesis of amyloid-beta (Aß) have reserved worsening particularly at late-stage human trials. Consequently, very few old drugs are presently used for AD with inadequate clinical consequences and various side effects. We focus on widespread pharmacological and beneficial principles for existing as well as future drugs. Multitargeting approaches by means of general antioxidant and anti-inflammatory mechanisms allied with particular receptor and/or enzyme-mediated actions in neuroprotection and neurodegeneration. The plant kingdom comprises a vast range of species with an incredible diversity of bioactive metabolites with diverse chemical scaffolds. In recent times, an increasing body of facts recommended the use of phytochemicals to decelerate AD's onset and progression. The definitive goal of AD investigation is to avert the onset of neurodegeneration, thereby allowing successful aging devoid of cognitive decline. At this point, we discussed the neurological protective role of natural products and naturally derived therapeutic agents for AD from various natural polyphenolic compounds and medicinal plants. In conclusion, medicinal plants act as a chief source of different bioactive constituents.

Chrysin: Sources, beneficial pharmacological activities, and molecular mechanism of action.

In recent years, public and scientific interest in plant flavonoids has tremendously increased because of their postulated health benefits. This review was mainly focuses on the flavone chrysin (5,7-dihydroxyflavone), which occurs naturally in many plants, honey, and propolis. A number of in vitro and in vivo studies have revealed the therapeutic effects of chrysin against various diseases. In general, chrysin exhibits many biological activities and pharmacological effects, including antioxidant, anti-inflammatory, anticancer, and antiviral activities. Moreover, many studies have reported on the bioavailability of chrysin. Because of its compromised bioavailability and enhanced protein stability, chrysin solid lipid nanoparticle (SLN) synthesis avoids proteolytic degradation and sustained release of drug delivery. To clarify the mechanism of action of chrysin, researchers have investigated the structural binding relationship of chrysin through the docking computation method.

Neuroprotective effect of chrysin on hyperammonemia mediated neuroinflammatory responses and altered expression of astrocytic protein in the hippocampus.

Neuroinflammation is an innate immune response in the central nervous system (CNS) against metabolic and pathogenic toxic wastes. The main hypothesis implies that a state of hyperammonemia which is accountable for both direct and indirect modification in ammonia metabolism with an elevated production of inflammatory cytokines. This study was constructed to explore the modulating effect of chrysin on rudimentary pathophysiologic mechanisms of ammonium chloride (NH4Cl) mediated neuroinflammation in the experimental hyperammonemic rats. NH4Cl was injected intraperitonally (i.p) in male albino wistar rats for a time period of thrice a week for eight consecutive weeks. Initially, the levels of brain ammonia and water content were assessed. Immunohistochemical, RT-PCR and western blotting analysis revealed that the expression of glutamine synthetase (GS) activity and glial fibrillar acidic protein (GFAP) were down-regulated, whereas the expression of TNF-α, IL-1ß, IL-6, p65 NF-κB, iNOS and COX-2 were up-regulated in brain tissue of hyperammonemic rats. Oral supplementation of chrysin (100mg/kg b.w) to hyperammonemic rats considerably restored the levels of brain ammonia, water content, and the expressions of GS, GFAP, TNF-α, IL-1ß, IL-6, p65 NF-κB, iNOS and COX-2. Our findings provided substantial evidence that the chrysin synergistically attenuating the neuroinflammatory mechanism by repressing the expression of proinflammatory cytokines and up-regulating the astrocytic protein expressions via ammonia-reducing strategies. This data suggests that chrysin effectively acts as a therapeutic agent to treat hyperammonemia mediated neuroinflammation.

Clinical aspects of urea cycle dysfunction and altered brain energy metabolism on modulation of glutamate receptors and transporters in acute and chronic hyperammonemia.

In living organisms, nitrogen arise primarily as ammonia (NH3) and ammonium (NH4(+)), which is a main component of the nucleic acid pool and proteins. Although nitrogen is essential for growth and maintenance in animals, but when the nitrogenous compounds exceeds the normal range which can quickly lead to toxicity and death. Urea cycle is the common pathway for the disposal of excess nitrogen through urea biosynthesis. Hyperammonemia is a consistent finding in many neurological disorders including congenital urea cycle disorders, reye's syndrome and acute liver failure leads to deleterious effects. Hyperammonemia and liver failure results in glutamatergic neurotransmission which contributes to the alteration in the function of the glutamate-nitric oxide-cGMP pathway, modulates the important cerebral process. Even though ammonia is essential for normal functioning of the central nervous system (CNS), in particular high concentrations of ammonia exposure to the brain leads to the alterations of glutamate transport by the transporters. Several glutamate transporters have been recognized in the central nervous system and each has a unique physiological property and distribution. The loss of glutamate transporter activity in brain during acute liver failure and hyperammonemia is allied with increased extracellular brain glutamate concentrations which may be conscientious for the cerebral edema and ultimately cell death.