Molecules of the plant world are proving their effectiveness in countering, slowing down, and regressing many diseases. The resveratrol for its intrinsic properties related to its stilbene structure has been proven to be a universal panacea, especially for a wide range of neurodegenerative diseases. This paper evaluates (in vivo and in vitro) the various molecular targets of this peculiar polyphenol and its ability to effectively counter several neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases and amyotrophic lateral sclerosis. What emerges is that, in the deep heterogeneity of the pathologies evaluated, resveratrol through a convergence on the protein targets is able to give therapeutic responses in neuronal cells deeply diversified not only in morphological structure but especially in their function performed in the anatomical district to which they belong.
Several diseases (such as diabetes, cancer, and neurodegenerative disorders) affect the morpho-functional aspects of red blood cells, sometimes altering their normal metabolism. In this review, the hematological changes are evaluated, with particular focus on the morphology and metabolic aspects of erythrocytes. Changes in the functionality of such cells may, in fact, help provide important information about disease severity and progression. The viral infection causes significant damage to the blood cells that are altered in size, rigidity, and distribution width. Lower levels of hemoglobin and anemia have been reported in several studies, and an alteration in the concentration of antioxidant enzymes has been shown to promote a dangerous state of oxidative stress in red blood cells. Patients with severe COVID-19 showed an increase in hematological changes, indicating a progressive worsening as COVID-19 severity progressed. Therefore, monitored hematological alterations in patients with COVID-19 may play an important role in the management of the disease and prevent the risk of a severe course of the disease. Finally, monitored changes in erythrocytes and blood, in general, may be one of the causes of the condition known as Long COVID.
The anti-proliferative activity of hesperetin, hesperidin, neohesperidin and rutin was evaluated on human hepatoma cell lines (Hep G2) and correlated to their antioxidant activity. The results obtained showed strong anti-proliferative effects of hesperidin and neohesperidin, considerably higher than the other two additives. Hesperetin induced caspase-3 activation, release of LDH and endogenous accumulation of putrescine. Cell cycle distribution seems to indicate that the inhibitory effects of polyphenols on cell growth could be due to G0/G1 block, and activation of apoptotic pathway in the presence of hesperetin. Our results underline also that the glycone forms show reduced scavenging activity against DPPH, but present a remarkable inhibition of cell proliferation and low cytotoxicity.
Bezafibrate belongs to the class of fibric acid derivatives usually used as antihyperlipidemia agents. From the biochemical point of view, these drugs show intriguing properties which leads one to think they may promote a differentiation process in tumour cells. This new pharmacological activity of fibrates could partially depend on the induction of an oxidative stress. To test this hypothesis, the effect of bezafibrate, as well as of clofibric acid and gemfibrozil, on growth, functional and cytochemical characteristics of human leukaemia-derived cell lines HL-60, U-937 and K-562 has been studied in some details. The results show that bezafibrate, gemfibrozil and clofibric acid, do induce differentiation in human myeloid leukaemia cell lines as indicated by several differentiation markers. Moreover fibrates, in dose dependent manner, significantly alter the cell cycle distributions, mainly leading to G 0 /G 1 phase increment and G 2 /M phase reduction. The differentiating activity of fibrates could have significant implications both for the pharmacotoxicological profile of this class of compounds and for the pathophysiology of neoplastic disease.
Sulfate transport by band-3 protein in adult human erythrocytes was shown to be modulated by oxygen pressure. In particular, a higher transport activity was measured under high oxygen pressure than at low one (0.0242+/-0.0073 vs. 0.0074+/-0.0010 min(-1)). Other factors, such as magnesium ions and orthovanadate, which can indirectly affect the binding properties of the cytoplasmic domain of band 3 (cdb3), influence significantly the anion exchanger activity. No effect of oxygen pressure on sulfate transport was found in chicken erythrocytes, which may be related to their lacking the cdb3 binding site. These findings are fully consistent with a molecular mechanism where the oxygen-linked transition of hemoglobin (T-->R) could play a key role in the regulation of anion exchanger activity.
The antioxidative activity of some natural flavonoids was analyzed against the stable free radical 2,2-diphenyl-1-picryhydrazyl. The results indicate that the scavenging power of the tested flavonols is higher than that of the synthetic antioxidants butylated hydroxyanisole and butylated hydroxytoluene; instead, the flavanones show little activity, as indicated by efficient concentration (EC50) values. Flavonoid autoxidation and interaction with Fe2+ and hydrogen peroxide were tested using erythrocyte membranes as a model. The results show that some compounds, like hesperetin, evidence a pro-oxidant activity higher than the ascorbic acid/iron reference system. The compounds with strong oxidative capability do not only influence cellular redox balance but also activate caspase-3, producing lactate dehydrogenase release and enhancing anionic exchange at the level of band 3 protein.
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