Flavonoids as Potential Therapeutics Against Neurodegenerative Disorders: Unlocking the Prospects.

Neurodegeneration, the decline of nerve cells in the brain, is a common feature of neurodegenerative disorders (NDDs). Oxidative stress, a key factor in NDDs such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease can lead to neuronal cell death, mitochondria impairment, excitotoxicity, and Ca2+ stress. Environmental factors compromising stress response lead to cell damage, necessitating novel therapeutics for preventing or treating brain disorders in older individuals and an aging population. Synthetic medications offer symptomatic benefits but can have adverse effects. This research explores the potential of flavonoids derived from plants in treating NDDs. Flavonoids compounds, have been studied for their potential to enter the brain and treat NDDs. These compounds have diverse biological effects and are currently being explored for their potential in the treatment of central nervous system disorders. Flavonoids have various beneficial effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic, and antioxidant properties. Their potential to alleviate symptoms of NDDs is significant.

Flavonoids and Alzheimer's disease: reviewing the evidence for neuroprotective potential.

Neurodegeneration, which manifests as several chronic and incurable diseases, is an age-related condition that affects the central nervous system (CNS) and poses a significant threat to the public's health for the elderly. Recent decades have experienced an alarming increase in the incidence of neurodegenerative disorders (NDDs), a severe public health issue due to the ongoing development of people living in modern civilizations. Alzheimer's disease (AD) is a leading trigger of age-related dementia. Currently, there are no efficient therapeutics to delay, stop, or reverse the disease's course development. Several studies found that dietary bioactive phytochemicals, primarily flavonoids, influence the pathophysiological processes underlying AD. Flavonoids work well as a supplement to manufactured therapies for NDDs. Flavonoids are effective in complementing synthetic approaches to treat NDDs. They are biologically active phytochemicals with promising pharmacological activities, for instance, antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor, anti-apoptotic, and antioxidant effects. The production of nitric oxide (NO), tumor necrosis factor (TNF-α), and oxidative stress (OS) are downregulated by flavonoids, which slow the course of AD. Hence, this research turned from preclinical evidence to feasible clinical applications to develop newer therapeutics, focusing on the therapeutic potential of flavonoids against AD.

Natural polymers as potential P-glycoprotein inhibitors: Pre-ADMET profile and computational analysis as a proof of concept to fight multidrug resistance in cancer.

P-glycoprotein (P-gp) is known as the "multidrug resistance protein" because it contributes to tumor resistance to several different classes of anticancer drugs. The effectiveness of such polymers in treating cancer and delivering drugs has been shown in a wide range of in vitro and in vivo experiments. The primary objective of the present study was to investigate the inhibitory effects of several naturally occurring polymers on P-gp efflux, as it is known that P-gp inhibition can impede the elimination of medications. The objective of our study is to identify polymers that possess the potential to inhibit P-gp, a protein involved in drug resistance, with the aim of enhancing the effectiveness of anticancer drug formulations. The ADMET profile of all the selected polymers (Agarose, Alginate, Carrageenan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid) has been studied, and binding affinities were investigated through a computational approach using the recently released crystal structure of P-gp with PDB ID: 7O9W. The advanced computational study was also done with the help of molecular dynamics simulation. The aim of the present study is to overcome MDR resulting from the activity of P-gp by using such polymers that can inhibit P-gp when used in formulations. The docking scores of native ligand, Agarose, Alginate, Carrageenan, Chitosan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid were found to be -10.7, -8.5, -6.6, -8.7, -8.6, -24.5, -6.7, -8.3, and -7.9, respectively. It was observed that, Cyclodextrin possess multiple properties in drug delivery science and here also demonstrated excellent binding affinity. We propose that drug efflux-related MDR may be prevented by the use of Agarose, Carregeenan, Chitosan, Cyclodextrin, Hyaluronic acid, and/or Polysialic acid in the administration of anticancer drugs.

Fluorescent-Nanoparticle-Impregnated Nanocomposite Polymeric Gels for Biosensing and Drug Delivery Applications.

Nanocomposite polymeric gels infused with fluorescent nanoparticles have surfaced as a propitious category of substances for biomedical purposes owing to their exceptional characteristics. The aforementioned materials possess a blend of desirable characteristics, including biocompatibility, biodegradability, drug encapsulation, controlled release capabilities, and optical properties that are conducive to imaging and tracking. This paper presents a comprehensive analysis of the synthesis and characterization of fluorescent-nanoparticle-impregnated nanocomposite polymeric gels, as well as their biomedical applications, such as drug delivery, imaging, and tissue engineering. In this discourse, we deliberate upon the merits and obstacles linked to these substances, encompassing biocompatibility, drug encapsulation, optical characteristics, and scalability. The present study aims to provide an overall evaluation of the potential of fluorescent-nanoparticle-impregnated nanocomposite polymeric gels for biomedical applications. Additionally, emerging trends and future directions for research in this area are highlighted.

Fast and Sensitive Bioanalytical Method for the Determination of Deucravacitinib in Human Plasma Using HPLC-MS/MS: Application and Greenness Evaluation.

Plaque psoriasis is a common, long-lasting illness that affects the immune system and causes significant negative impacts on a patient's physical health, well-being, and ability to work effectively. Deucravacitinib (DEU) is the first oral medication used in the treatment of plaque psoriasis, a chronic skin condition that causes red, scaly patches on the skin. DEU is a type of medication called an oral Janus kinase (JAK) inhibitor, which works by blocking specific enzymes that play a role in the inflammation and immune response associated with psoriasis. Therefore, a quick, easy, novel, reliable, sensitive, and straightforward liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was used to analyze DEU in plasma samples. The LC-MS/MS method for the determination of DEU in human plasma was based on using trimethoprim as an internal standard (IS). The separation of DEU and IS was carried out via liquid-liquid extraction (LLE). The extract was then subjected to the chromatographic system separation using the ACE-C18 column (4.6 × 100 mm, 5 µm). The mobile phase employed consisted of methanol and a solution of 2 mM ammonium formate (80:20 v/v, respectively). The flow rate used was set at 0.9 mL min-1. The creative strategy was performed by running an ABSCIEX API 4000 mass spectrometer with an electron spray ionization source in multiple reaction monitoring (MRM) mode. The ion transitions m/z 426.3 → 358.2 were used for DEU quantitation, while the ion transitions m/z 291.1 → 261.1 were used for trimethoprim quantitation. The accuracy, precision, linearity, recovery, and selectivity of DEU were deemed acceptable when validated for a concentration range between 0.500 and 601.050 ng/mL, utilizing a weighting factor of 1/x2.

Fighting Antibiotic Resistance: New Pyrimidine-Clubbed Benzimidazole Derivatives as Potential DHFR Inhibitors.

The present work describes the design and development of seventeen pyrimidine-clubbed benzimidazole derivatives as potential dihydrofolate reductase (DHFR) inhibitors. These compounds were filtered by using ADMET, drug-likeness characteristics calculations, and molecular docking experiments. Compounds 27, 29, 30, 33, 37, 38, and 41 were chosen for the synthesis based on the results of the in silico screening. Each of the synthesized compounds was tested for its in vitro antibacterial and antifungal activities using a variety of strains. All the compounds showed antibacterial properties against Gram-positive bacteria (Staphylococcus aureus and Staphylococcus pyogenes) as well as Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Most of the compounds either had a higher potency than chloramphenicol or an equivalent potency to ciprofloxacin. Compounds 29 and 33 were effective against all the bacterial and fungal strains. Finally, the 1,2,3,4-tetrahydropyrimidine-2-thiol derivatives with a 6-chloro-2-(chloromethyl)-1H-benzo[d]imidazole moiety are potent enough to be considered a promising lead for the discovery of an effective antibacterial agent.

Recent advancements on hyperthermia driven controlled drug delivery from nanotherapeutics.

Previous reviews of the works on magnetic nanoparticles for hyperthermia induced treatment concentrated mostly on magnetic fluid hyperthermia (MFH) employing monometallic/metal oxide nanocomposites. In the literature, the word "hyperthermia" was also limited to the use of heat for medicinal purposes. A number of publications have recently been published demonstrating that magnetic nanoparticle-based hyperthermia may produce restricted high temperatures, resulting in the release of medicines that are either connected to the magnetic nanoparticles or encased in polymer matrices. In this debate, we propose broadening the concept of "hyperthermia" to encompass temperature-based treatment as well as magnetically controlled medication delivery. The review also addresses core-shell magnetic nanomaterials, particularly nanoshells made by stacked assembly, for the use of hyperthermia-based treatment and precise administration of drugs. The primary objective of this review article is to demonstrate how the combination of hyperthermia-induced therapy and 'on demand' drug release models may lead to effective applications in personalized medicine.

Preparation and evaluation of transdermal naproxen niosomes: formulation optimization to preclinical anti-inflammatory assessment on murine model.

The present study was designed with an aim to develop and optimize naproxen proniosomes (NAPRNs) using Box-Behnken Design (BBD). The formulation was optimized using three independent variables [maltodextrin (X1), surfactant concentration (X2) and drug concentration (X3)] at three different levels (low, medium and high). The prepared fifteen formulations were evaluated for drug entrapment efficiency, vesicle size and transdermal flux to select the optimized naproxen niosomes (NAPRNopt). The developed NAPRNs formulations showed the nano-size vesicle (218-417 nm) and high encapsulation efficiency (60.48-92.48%) with high flux value (23.17-27.37 µg/cm2/h). The formulation NAPRNopt has shown the vesicle size of 376.12 ± 4.12 nm with entrapment efficiency 86.43 ± 3.63% and transdermal flux of 27.56 ± 1.43 µg/cm2/h. The SEM study revealed the formulation NAPRNopt showed irregular surface morphology of niosomes. The formulation NAPRNopt gel showed biphasic release behaviour as an initial fast release and later slower release with the Higuchi release mechanism. The anti-inflammatory study results showed a better effect than the standard NAP gel in the rat model.