Silibinin is a flavonoid extracted from the medicinal plant Silybum marianum (milk thistle), traditionally used to treat liver disease. Recent studies have shown that the antioxidative stress and anti-inflammatory effects of milk thistle are used in the treatment of neurological diseases. Silibinin has antioxidative stress and antiapoptotic effects and reduces cognitive impairment in models of Alzheimer’s disease (AD). However, the underlying mechanism of silibinin related to improvement of cognition remains poorly understood. In this study, we used the model of lateral ventricle injection of formaldehyde to examine the related mechanism of silibinin in improving cognitive impairment disorders. Oral administration of silibinin for three weeks significantly attenuated the cognitive deficits of formaldehyde-induced mice in a Y -maze test and Morris water maze test. Y -maze results show that silibinin increases the rate of spontaneous response alternation in FA-induced mice. Silibinin increases the target quadrant spending time and decreases escape latency in the Morris water maze test. We examined the effect of silibinin on the NRF2 signaling pathway, and silibinin promoted the nuclear transfer of NRF2 and increased the expression of HO-1 but did not significantly increase the protein expression of NRF2 in the hippocampus. Well, silibinin reduces the content of DHE and decreases the levels of apoptosis of mature neuron cells. We investigated the effect of silibinin on the content of formaldehyde degrading enzymes; biochemical analyses revealed that silibinin increased GSH and ALDH2 in formaldehyde-induced mice. In addition, as one of the pathological changes of AD, TAU protein is also hyperphosphorylated in FA model mice. Silibinin inhibits the expression of GSK-3β in model mice, thereby reducing the phosphorylation of TAU proteins ser396 and ser404 mediated by GSK3β. Based on our findings, we verified that the mechanism of silibinin improving cognitive impairment may be antioxidative stress, and silibinin is one of the potentially promising drugs to prevent formaldehyde-induced cognitive impairment.
Parkinson's disease (PD) is a well-known neurodegenerative disorder associated with a high risk in middle-aged and elderly individuals, severely impacting the patient's quality of life. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is frequently used to establish PD in animals. Dendritic spines are dendritic processes that form the foundation of learning and memory. Reportedly, dendritic spine density of striatal medium spiny neurons (MSNs) declines in PD, and this decline has been associated with PD progression; however, the underlying mechanism remains elusive. Herein, we used the MPTP animal model to examine whether serum-induced kinase (SNK) and spineassociated Rap guanosine triphosphatase (SPAR) contribute to decreased dendritic spine density in striatal MSNs. MPTP was used to establish the animal model, which exhibits motor function impairment and dopaminergic cell loss. To assess spine density, Golgi staining was performed to count striatal dendritic spines, which were reduced in the MPTP group when compared with those in the normal control group. Immunohistochemistry was performed to analyze changes in SNK and SPAR expression. MPTP treatment significantly increased the expression of SNK in striatal MSNs, whereas that of SPAR was significantly decreased when compared with the normal control group. These findings offer clues to further explore the mechanism of declining dendritic spine density in patients with PD and provide evidence for potential target identification in PD.
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