Silibinin-Albumin Nanoparticles: Characterization and Biological Evaluation Against Oxidative Stress-Stimulated Neurotoxicity Associated with Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is strongly associated with oxidative stress which can damage neural cells. Silibinin has shown potential antioxidative effects. However, due to its low solubility in water, silibinin provides low biological activity and bioavailability. Therefore, to increase its pharmacological effects, silibilin was encapsulated into human serum albumin (HSA) nanoparticles and well-characterized by DLS and TEM techniques. The antioxidant activity of silibinin-HSA nanoparticles was evaluated on LPS-induced oxidative stress in neuron-like cells (SH-SY5Y) through MTT, antioxidant activity and apoptotic assay. It was shown that the mean diameter of HSA and silibinin-HSA nanoparticles were 88 and 105 nm, respectively with a drug loading of 24.08%, drug encapsulation rate of 94.72%, and the yield of silibinin-HSA nanoparticles of around 83.41% and the HSA nano-formulation released silibinin for 15 h. The results displayed that cell viability was reduced by LPS (10 μg/mL), who’s also determined to stimulate oxidative stress and apoptosis. However, co-incubation of cells with silibinin (50 μg/mL) or silibinin-HSA nanoparticles led to the recovery of cell viability, activation of SOD and CAT, increase of GSH content, and reduction of ROS level, Caspase-3 activity and fragmentation of DNA. It was also indicated that the neuroprotective and antioxidant activities of silibinin-HAS nanoparticles was greater than free silibinin, indicating that using albumin can be a potential formulation approach for improving the antioxidant efficacy of silibinin.

Silibinin Ameliorates Formaldehyde-Induced Cognitive Impairment by Inhibiting Oxidative Stress

“…In this study, we found that silibinin improved FA-induced cognitive impairments and inhibited FA-induced oxidative stress. Silibinin has been reported to ameliorate AD by multiple mechanisms such as inhibition of acetylcholinesterase activity, restrain of amyloid β peptide aggregation, regulation of gut microbiota, and suppression of oxidative stress [ 58 , 60 – 63 ]. Importantly, accumulating evidence and our previous study suggest that silibinin ameliorated memory impairments in AD-like mice via suppression of oxidative stress [ 14 , 15 , 62 , 63 ].…”

“…Silibinin has been reported to ameliorate AD by multiple mechanisms such as inhibition of acetylcholinesterase activity, restrain of amyloid β peptide aggregation, regulation of gut microbiota, and suppression of oxidative stress [ 58 , 60 – 63 ]. Importantly, accumulating evidence and our previous study suggest that silibinin ameliorated memory impairments in AD-like mice via suppression of oxidative stress [ 14 , 15 , 62 , 63 ]. Similarly, in present study, we found that silibinin alleviated cognitive impairments probably via inhibiting oxidative stress in FA-treated mice.…”

Protective Effect of NGR1 against Glutamate-Induced Cytotoxicity in HT22 Hippocampal Neuronal Cells by Upregulating the SIRT1/Wnt/β-Catenin Pathway

“…Oxidative stress caused by the accumulation of reactive oxygen species (ROS) in nerve cells is associated with neurological complications, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and neuropathic pain [ 15 – 17 ]. The antioxidants are the first defense to detoxify ROS [ 14 ].…”

The Role of a Pathological Interaction between β-amyloid and Mitochondria in the Occurrence and Development of Alzheimer’s Disease

“…The effect of silibinin encapsulated in the nanoparticles of human serum albumin (HSA) was also studied. The neuroprotective and antioxidant activity of silibinin–HSA nanoparticles was found to be higher than that of free silibinin [ 188 ]. Another flavonoid, quercetin, which modulates gene expression and the signaling pathways, also exhibits antioxidant and iron chelating activities [ 189 ].…”