Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel

Alzheimer, a neurodegenerative disease, and a large variety of pathologic conditions are associated with a form of protein aggregation known as amyloid fibrils. Since fibrils and prefibrillar intermediates are cytotoxic, numerous attempts have been made to inhibit fibrillation process as a therapeutic strategy. Peptides, surfactants and aromatic small molecules have been used as fibrillation inhibitors. Here we studied the effects of paclitaxel, a polyphenol with a high tendency for interaction with proteins, on fibrillation of insulin as a model protein. The effects of paclitaxel on insulin fibrillation were determined by Thioflavin T fluorescence, Congo red absorbance, circular dichroism and atomic force microscopy. These studies indicated that paclitaxel considerably hindered nucleation, and therefore, fibrillation of insulin in a dose-dependant manner. The isothermal titration calorimetry studies showed that the interaction between paclitaxel and insulin was spontaneous. In addition, the van der Waal's interactions and hydrogen bonds were prominent forces contributing to this interaction. Computational results using molecular dynamic simulations and docking studies revealed that paclitaxel diminished the polarity of insulin dimer and electrostatic interactions by increasing the hydrophobicity of its dimer state. Furthermore, paclitaxel reduced disrupting effects of insulin fibrils on PC12 cell's neurite outgrowth and complexity, and enhanced their survival. © 2014 The Authors 2014

Silymarin-albumin nanoplex: preparation and its potential application as an antioxidant in nervous system in vitro and in vivo

In this study, we formulated silymarin-HSA nanoplex and assayed its ability to reduce LPSinduced toxicity in vitro and in vivo. Silymarin molecules were encapsulated into HSA nanoplex and the loading efficiency and characterization of fabricated nanoplex were performed by using HPLC, TEM, SEM, DLS, FTIR analysis, and theoretical studies. Afterwards, their protective effect against LPS (20 µg/ml) -induced toxicity in SH-SY5Y cells was investigated by MTT, ROS, and apoptosis assays. For in vivo experiments, rats were pre-treated with either silymarin or silymarin -HSA nanoplex (200 mg/kg) orally for 3 days and at third day received LPS by IP at a dose of 0.5 mg/kg, 150 min before scarification followed by SOD and CAT activity assay. The formulation of silymarin-HSA nanoplex showed a spherical shape with an average diameter between 50 nm to 150 nm, hydrodynamic radius of 188.3 nm, zeta potential of -26.6 mV, and a drug loading of 97.3%. In LPS-treated cells, pretreatments with silymarin-HSA noncomplex recovered the cell viability and decreased the ROS level and corresponding apoptosis more significantly than free silymarin. In rats, it was also depicted that, silymarin-HSA noncomplex can increase the SOD and CAT activity in brain tissue at LPS-triggered oxidative stress model more significantly than free counterpart. Nanoformulation of silymarin improved its capability to reduce LPS-induced oxidative stress by restoring cell viability and elevation of SOD and CAT activity in vitro and in vivo, respectively. Therefore, formulation of silymarin may hold a great promise in the field of antioxidant agent development

The urgent need for integrated science to fight COVID-19 pandemic and beyond

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also afects society as a whole; so, it has also become the leading scientifc concern. We discuss in this treatise the importance of bringing the world’s scientists together to fnd efective solu‑ tions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic’s consequences and prevent recurrences of similar pandemics

Investigating the human hemoglobin fructation in the presence of propolis in vitro

Background: Propolis is a complex resinous mixture that is gathered and processed by honeybees from resin they collect from trees and plants. This substance has various biological properties. Glycation is a reaction, which occurs between a protein and a reducing sugar and finally causes structural alterations and destruction of proteins. The role of glycation has been approved in the development and aggravation of diabetic complications. This study aimed to examine the effect of ethanolic extract of propolis (EEP) on fructation and destruction of hemoglobin protein structure. Materials and Methods: In this experimental study, purified hemoglobin was incubated alone and with fructose in the presence and absence of different concentrations of EEP (10, 20 and 40µg/ml) for 5 weeks. The extent of hemoglobin fructation was determined by measuring the amount of heme release, blue shift in soret band, releasing the products of heme destruction and assessing the amyloid structures using the UV-visible and fluorescence spectroscopy. Results: Incubation of hemoglobin with fructose was led to the hemoglobin destruction and heme release. Hemoglobin fructation was inhibited up to 45 in the presence of EEP with a concentration of 40µg/ml. The two lower concentrations of EEP showed the lower degrees of inhibition. Moreover, fluorescence studies of products resulting from heme degradation and fibrillar structures are indicative of the reduction in hemoglobin fructation in the presence of EEP. Conclusion: Hemoglobin is drastically glycated in the presence of fructose and EEP can decrease the hemoglobin fructation in a concentration-dependent manner

A novel method for thermodynamic study on the binding of milk carrier protein of BLG-A with Cr+3

Thermodynamics of the interaction between Cr3+ with β-lactoglobulin type A (BLG-A) was investigated at pH 7.0 and 37°C by isothermal titration calorimetry. A new method to follow the effect of Cr3+ on the stability of BLG-A was introduced. The new solvation model was used to reproduce the enthalpies of BLG-A+ Cr3+ interactions over the whole range of Cr3+ concentrations. The solvation parameters recovered from the new equation are attributed to the structural change of BLG-A and its biological activity. The results obtained indicate that there is a set of two identical binding sites for Cr3+ ions with positive cooperativity. The association equilibrium constants are 14.39 and 0.49 mM-1 for the first and second binding site, respectively. The enthalpy of binding for one mole of Cr+3 ion to one mole of the binding site on BLG-A (ΔH=104.60 kJ mol-1) is obtained

Curcumin mitigates the fibrillation of human serum albumin and diminishes the formation of reactive oxygen species

The formation of amyloid fibrils are thought to contribute to pathogenesis of many amyloids associated human diseases. Here the impact of curcumin on amyloid formation of human serum albumin (HSA) was studied. Incubation of HSA at 68°C under physiologic pH led to amyloid fibril formation. Thioflavin T (ThT) fluorescence was used for determination of amyloid fibril formation. Atomic force microscopy experiments indicated different fibril structure of HSA incubated with or without curcumin. The monitoring of the changes in reactive oxygen species (ROS) levels upon incubation of curcumin with HSA showed a significant decrease in ROS levels. Similar experiments were also carried out in the presence of aflatoxin M1 (AFM1) and lead (Pb) ions. Our results indicated that AFM1 and Pb ions promote the fibrillation of HSA and accelerate ROS production, which were inhibited in the presence of curcumin. Thus, curcumin mitigates protein fibrillation activity and diminishes ROS generation. © 2015 Bentham Science Publishers