RESUMO
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.
RESUMO
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.
RESUMO
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.