No abstract

Taxifolin is a kind of flavanonol, whose biological ability. The objectives of this study were to investigate the antioxidants and antiradical activities of taxifolin by using different in vitro bioanalytical antioxidant methods including DMPD√(+), ABTS√(+), [Formula: see text], and DPPH√-scavenging effects, the total antioxidant influence, reducing capabilities, and Fe(2+)-chelating activities. Taxifolin demonstrated 81.02% inhibition of linoleic acid emulsion peroxidation at 30 µg/mL concentration. At the same concentration, standard antioxidants including trolox, α-tocopherol, BHT, and BHA exhibited inhibitions of linoleic acid emulsion as 88.57, 73.88, 94.29, and 90.12%, respectively. Also, taxifolin exhibited effective DMPD√(+), ABTS√(+), [Formula: see text], and DPPH√-scavenging effects, reducing capabilities, and Fe(2+)-chelating effects. The results obtained from this study clearly showed that taxifolin had marked antioxidant, reducing ability, radical scavenging and metal-chelating activities. Also, this study exhibits a scientific shore for the significant antioxidant activity of taxifolin and its structure-activity insight.

No abstract

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder, characterized by the formation, aggregation and accumulation of amyloid beta, perturbed metal (copper, iron and zinc) homeostasis, metal-induced oxidative stress, neuroinflammation, aberrant activity of acetylcholinesterase (AChE) and other pathologies. The aim of this review is to discuss the current therapies based on the "combination-drugs-multitargets" strategy to target multiple pathologies to block the progression of pathogenesis of AD. In addition to cholinergic and amyloid targets, a significant effort is focused on targeting the metal-induced oxidative stress component of the disease. The main focus of research is based on modifications of existing drugs with specific biological activity. Tacrine was the first AChE inhibitor to be introduced into clinical practice and has been frequently used for the design of multitarget-directed ligands. A number of hybrid compounds containing tacrine and structural moieties derived from natural sources such as flavonoids [quercetin, rutin, coumarin, gallamine, resveratrol, scutellarin, anisidine, hesperetin, (−)-epicatechin] and other molecules (melatonin, trolox) have also been applied to function as multitarget-directed ligands. Most of these hybrids are potent inhibitors of AChE and butyrylcholinesterase and also of amyloid-beta aggregation. In addition, the antioxidant functionality, represented by coumarins, melatonin and other antioxidant molecules reduces the level of oxidative stress via ROS-scavenging mechanisms, as well as via chelation of redox-active Cu and Fe, thus suppressing the formation of ROS via the Fenton reaction. Various medicinal plants are under investigation for their ability to ameliorate symptoms of AD. The therapeutic potency of huperzine A and B, ginseng, curcumin and other compounds is manifested predominantly by the inhibitory action toward AChE, antioxidant or radical-scavenging and redox metal-chelating activity, inhibition of amyloid-beta aggregation and tau-protein hyperphosphorylation and antiinflammatory activity. Flavonoids not only function as antioxidants and metal-chelating agents, but also interact with protein kinase and lipid kinase signaling pathways, and others involving mitogen-activated protein kinase, NF-kappaB and tyrosine kinase. Among the most promising group of substances with potential activity against AD are the flavonoids, including myricetin, morin, rutin, quercetin, fisetin, kaempferol, apigenin and glycitein, which have been shown, in vitro, to possess antiamyloidogenic and fibril-destabilization activity, as well as being able to act as metal chelators and to suppressing oxidative stress. In terms of the clinical use of multifunctional hybrids, herbal drugs or flavonoids against AD, some remaining challenges are to establish the ideal dose to develop effective formulations to preserve bioavailability and to determine the stage when they should be administered. If the onset of the disease could be delayed by a decade, the number of AD vic...

Heavy metals are essential for a wide range of biological processes, including the growth and reproduction of cells, synthesis of biomolecules, many enzymatic reactions, and the body’s immunity, but their excessive intake is harmful. Specifically, they cause oxidative stress (OS) and generate free radicals and reactive oxygen species (ROS) in metabolism. In addition, the accumulation of heavy metals in humans can cause serious damage to different organs, especially respiratory, nervous and reproductive and digestive systems. Biologically, metal chelation therapy is often used to treat metal toxicity. This process occurs through the interaction between the ligand and a central metal atom, forming a complex ring-like structure. After metals are chelated with appropriate chelating agents, their damage in metabolism can be prevented and efficiently removed from the body. On the other hand, heavy metals, including Zn, Fe and Cu, are necessary for the suitable functioning of different proteins including enzymes in metabolism. However, when the same metals accumulate at levels higher than the optimum level, they can easily become toxic and have harmful effects toward biomolecules. In this case, it induces the formation of ROS and nitrogen species (RNS) resulting in peroxidation of biological molecules such as lipids in the plasma membrane. Antioxidants have an increasing interest in many fields due to their protective effects, especially in food and pharmaceutical products. Screening of antioxidant properties of compounds needs appropriate methods including metal chelating assay. In this study, a general approach to the bonding and chelating properties of metals is described. For this purpose, the basic principles and chemical principles of metal chelation methods, both in vivo and in vitro, are outlined and discussed. Hence, in the main sections of this review, the descriptions related to metal ions, metal chelating, antioxidants, importance of metal chelating in biological system and definitions of metal chelating assays as widely used methods to determine antioxidant ability of compounds are provided. In addition, some chemical properties, technical and critical details of the used chelation methods are given.