Natural silibinin modulates amyloid precursor protein processing and amyloid-β protein clearance in APP/PS1 mice

Abstract

Silibinin has been shown to attenuate cognitive dysfunction and inhibit amyloid-beta (Aβ) aggregation in Alzheimer's disease (AD) models. However, the underlying mechanism by which silibinin improves cognition remains poorly understood. In this study, we investigated the effect of silibinin on β-secretase levels, Aβ enzymatic degradation, and oxidative stress in the brains of APP/PS1 mice with cognitive impairments. Oral administration of silibinin for 2 months significantly attenuated the cognitive deficits of APP/PS1 mice in the Y-maze test, novel object recognition test, and Morris water maze test. Biochemical analyses revealed that silibinin decreased Aβ deposition and the levels of soluble Aβ1-40/1-42 in the hippocampus by downregulating APP and BACE1 and upregulating NEP in APP/PS1 mice. In addition, silibinin decreased the MDA content and increased the activities of the antioxidant enzymes CAT, SOD, and NO. Based on our findings, silibinin is a potentially promising agent for preventing AD-associated Aβ pathology.

Impact of Silibinin A on Bioenergetics in PC12APPsw Cells and Mitochondrial Membrane Properties in Murine Brain Mitochondria

“…Based on the penetration coefficients, the tested SIL formulation was characterized as a moderately absorbed group of compounds and only Euromed could be considered a good candidate to cross the blood-brain-barrier (BBB) [74]. However, several in vivo studies used non-formulated SIL to investigate its effects on the brain [23,[75][76][77][78][79][80].…”

Silibinin Ameliorates Formaldehyde-Induced Cognitive Impairment by Inhibiting Oxidative Stress

“…Mice were randomly divided into five groups: sham group, FA 2 mM group, FA 2 mM + silibinin 100 mg/kg group, FA2mM + silibinin 200 mg/kg group, and the memantine 2.6 mg/kg group. The dose of silibinin in this study was based on our previous study [ 14 , 15 ]. There were ten mice per group with five males and five females each.…”

“…The Y -maze test was performed after 14 days of intracerebroventricular injection as described in our previous report [ 14 ]. The maze was composed of three arms (A, B, and C).…”

“…Mice were trained twice a day for five consecutive days with an intertrial interval of 6 h. Animals were placed in the water facing the wall individually and were allowed 60 s to find the hidden platform. If the mouse failed to find the platform, the experimenter placed the mouse on the platform for 10 s. The platform was removed on the sixth day; mice were individually administered a probe test as in a previous experiment [ 14 ]. A computer system (equipped with a video camera) automatically captured the escape latency (time spent in the target quadrant) and swimming distance.…”

“…In addition, silibinin can act as an antioxidant to combat oxidative stress-related neuropathy [ 13 ]. The results of our previous studies have shown that silibinin reduces A β deposition and has anti-inflammatory and antiapoptotic effects that improve cognitive impairment in AD model mice [ 14 , 15 ]. In this work, we used intracerebroventricular injection of formaldehyde in C57 mice as an animal model for three weeks of continuous administration to explore the effect of silibinin on improving spatial learning and memory impairment and its related mechanisms.…”