Neurochemical Ameliorating of the Hippocampus in Dyslipidemic Alzheimer Patients Following Silymarin; a Double-Blind Placebo-Controlled Randomized Clinical Trial.

Abstract

Background: Amyloid-beta (Aβ) production is a normal physiological process, and an imbalance in Aβ production/excretion rate is the basis of the plaque load increase in AD. LRP1 is involved in both central clearance of Aβ from the CNS and transport of Aβ toward peripheral organs. In this study, the effect of silymarin combination compared to rosuvastatin and placebo on neuro-metabolites and serum levels of LRP1 and Aβ1-42 proteins and oxidative stress enzymes and lipid and cognitive tests of Iranian AD patients.

Methods: In this double-blind placebo-controlled study, thirty-six mild AD patients were divided into groups (n=12) of silymarin 140mg, placebo, and rosuvastatin 10mg. Medications were administered 3 times a day for 6 months. Clinical tests, lipid profile (TG, HDL, TC, and LDL), Aβ1-42, and LRP1 markers were measured at the beginning and end of the intervention. Magnetic resonance spectroscopy (MRS) was used to measure metabolites. Using SPSS software a one-way ANOVA test was used to compare the means of the quantitative variables and Pearson and Spearman's correlations to measure the correlation. GraphPad Prism software was used for drawing graphs. P < 0.05 was considered a significant.

Results: The levels of LRP1 and Aβ1-42 in the silymarin group were significantly increased compared to the other groups (P < 0.05). NAA/mI in the silymarin group had a significant increase compared to both placebo and rosuvastatin groups (P < 0.05). Right and left hippocampal mI/Cr directly correlated with TG (r = 0.603, P = 0.003 and r = 0.595, P = 0.004, respectively). NAA/Cr of the right and left hippocampus was inversely related to TG (r = -0.511, P = 0.0033, and r = -0.532, P = 0.0021, respectively). NAA/Cr and NAA/mI of bilateral hippocampi directly correlated with HDL (P < 0.05). An inverse correlation was observed between the Aβ1-42 and mI/Cr of the right and left hippocampus (r = -0.661, P = 0.000 and r = -0.638, P = 0.000, respectively).

Conclusion: Donepezil and silymarin improved lipid profile associated with increased NAA/Cr, and decreased mI/Cr, in AD patients. Biomarker NAA/mI can be clinically significant in examining AD pathology. Measurement of the lipid factors and neurometabolites can be a suitable method for monitoring this disease.