Silibinin Ameliorates Formaldehyde-Induced Cognitive Impairment by Inhibiting Oxidative Stress

Abstract

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.

Berberine attenuates cognitive dysfunction and hippocampal apoptosis in rats with prediabetes

“…Since neuronal cells are sensitive to oxidative damage (Yin et al., 2016), neuronal cells will be damaged once there is a bioenergetic defect or mitochondrial dysfunction, resulting in cognitive dysfunction (Trigo et al., 2022). Oxidative stress is one of the triggers of apoptosis (Wei et al., 2022), and apoptosis of neuronal cells in the hippocampus is one of the causes of cognitive dysfunction (Wang et al., 2017). This may also be a culprit for the volume reduction of hippocampal tissue in prediabetes (Dong et al., 2019).…”

Protective Effect of Hedeoma drummondii against Formaldehyde-Induced Testicular Toxicity and Genotoxicity in Wistar Rats

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Dual effects of endogenous formaldehyde on the organism and drugs for its removal

“…By stimulating the Nrf2 pathway, silymarin increases cellular resilience to oxidative stress and apoptosis and reduces cognitive impairment, thus reducing the negative effects of endogenous FA on the neurological system. To create a model of endogenous FA accumulation, Wei et al (2022) used an intracerebroventricular injection of FA in C57 mice. They discovered that continuous administration for 3 weeks significantly reduced FA‐induced cognitive deficits in the y‐maze and MWM tests.…”