Effect of silibinin and trans-chalcone in an Alzheimer's disease-like model generated by insulin amyloids

Amyloid fibrils are characteristic of several disorders including Alzheimer's disease (AD), with no cure or preventive therapy. Diminishing amyloid deposits using aromatic compounds is an interesting approach toward AD treatment. The present study examined the anti-fibrillogenic effects of silibinin and trans-chalcone in vitro, in vivo, and in silico on insulin amyloids. In vitro incubation of insulin at 37°C for 24 h induced amyloid formation. Addition of trans-chalcone and silibinin to insulin led to reduced amounts of fibrils as shown by thioflavin S fluorescence and Congo red absorption spectroscopy, with a better effect observed for silibinin. In vivo bilateral injection of fibrils formed by incubation of insulin in the presence or absence of silibinin and trans-chalcone or insulin fibrils plus the compounds in rats' hippocampus was performed to obtain AD characteristics. Passive avoidance (PA) test showed that treatment with both compounds efficiently increased latency compared with the model group. Histological investigation of the hippocampus in the cornu ammonis (CA1) and dentate gyrus (DG) regions of the rat's brain stained with hematoxylin-eosin and thioflavin S showed an inhibitory effect on amyloid aggregation and markedly reduced amyloid plaques. In silico, a docking experiment on native and fibrillar forms of insulin provided an insight onto the possible binding site of the compounds. In conclusion, these small aromatic compounds are suggested to have a protective effect on AD.

Nano-composition of riboflavin-nafion functional film and its application in biosensing.

A novel nafion-riboflavin membrane was constructed and characterized by the scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV-visible spectroscopy and cyclic voltammetric techniques. The estimated average diameter of the designed nanoparticles was about 60 nm. The functional membrane showed a quasi-reversible electrochemical behaviour with a formal potential of -562 +/- 5 mV (vs Ag/AgCl) on the gold electrode. Some electrochemical parameters were estimated, indicating that the system has good and stable electron transfer properties. Moreover, horseradish peroxidase (HRP) was immobilized on the riboflavin-nafion functional membrane. The electrochemical behaviour of HRP was quasi-reversible with a formal potential of 80 +/- 5 mV (vs Ag/AgCl). The HRP in the film exhibited good catalytic activity towards the reduction of H2O2. It shows a linear dependence of its cathodic peak current on the concentration of H2O2, ranging from 10 to 300 (micro)M.

[Effect of HMG-CoA reductase and ACAT inhibition on protein and phospholipid contents of VLDL1 and VLDL2 in guinea pig model]

Objective: To compare the effect of HMG-CoA reductase and ACAT inhibition on the protein and phospholipid contents of perfusate VLDL1 and VLDL2

Design: Experimental study

Animal: Guina pig

Procedure: After anesthesia and abdominal surgery, guinea pig liver was perfused by Krebs-Henslite buffer through completely closed perfusion system.In continue the effect of progesterone, lovastatin and progesterone plus lovastatin on the perfusate VLDL1 and VLDL2 contents was studied.For this reason, VLDL fractions were separarted by cumulative flotation ultracentrifugation ,confirmed by electrone microscopy and in each pool total protein[TOP], total lipid and phospholipid [PL] were measured

Statistical analysis: Percent of 90 minute point mean secretion were compared among different treatment groups by ANOVA.Moreover, slope linear regression between each of treatment group and control was analyzed by t-student test

Results: Progesterone has no significant effect on total lipid,TOP and PL contents of VLDL1 while percent slope changes of linear regression for VLDL2 contents show a significant decrease in lovastatin treatment group [P<0.05]. Lovastatin lowers total lipid [by 20%] in VLDLI and [by 41%] in VLDL2.PL decrease is 20% in VLDL1 and 39% VLDL2.These changes in Progesterone plus lovastatin treatment group are 20% and 40% for total lipid and 21% and 44% for phospholipid

Clinical implications: The effect of HMG-CoA reductase inhibitors on smaller VLDL2 is more than larger VLDL1.These findings are important for using of LDL animal as a model for studying of lipoprotein disorders