Abstract
Background: Accumulating studies have confirmed that oxidative stress leads to the death of neuronal cells and is associated with the progression of neurodegenerative diseases, including Alzheimer's disease (AD). Despite the compelling evidence, there is a drawback to the use of the antioxidant approach for AD treatment, partly due to limited blood-brain barrier (BBB) permeability. Phytosterol is known to exhibit BBB penetration and exerts various bioactivities such as antioxidant and anticancer effects, and displays a potential treatment for dyslipidemia, cardiovascular disease, and dementia.Objective: In this study, the protective effects of stigmasterol, a phytosterol compound, on cell death induced by hydrogen peroxide (H2O2) were examined in vitro using human neuronal cells (SH-SY5Y cells).Methods: MTT assay, reactive oxygen species measurement, mitochondrial membrane potential assay, apoptotic cell measurement, and protein expression profiles were performed to determine the neuroprotective properties of stigmasterol.Results: H2O2 exposure significantly increased the levels of reactive oxygen species (ROS) within the cells thereby inducing apoptosis. On the contrary, pretreatment with stigmasterol maintained ROS levels inside the cells and prevented oxidative stress-induced cell death. It was found that pre-incubation with stigmasterol also facilitated the upregulation of forkhead box O (FoxO) 3a, catalase, and anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) in the neurons. In addition, the expression levels of sirtuin 1 (SIRT1) were also increased while acetylated lysine levels were decreased, indicating that SIRT1 activity was stimulated by stigmasterol, and the result was comparable with the known SIRT1 activator, resveratrol.Conclusion: Taken together, these results suggest that stigmasterol could be potentially useful to alleviate neurodegeneration induced by oxidative stress.
Highlights
Oxidative stress occurs in many human diseases as a result of the imbalance between high levels of reactive oxygen species (ROS) production and insufficient antioxidant defense resulting in lipid peroxidation, cellular membrane impairment, protein degradation, and DNA damage [1]
It was found that pre-incubation with stigmasterol facilitated the upregulation of forkhead box O (FoxO) 3a, catalase, and anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) in the neurons
The expression levels of sirtuin 1 (SIRT1) were increased while acetylated lysine levels were decreased, indicating that SIRT1 activity was stimulated by stigmasterol, and the result was comparable with the known SIRT1 activator, resveratrol
Summary
Oxidative stress occurs in many human diseases as a result of the imbalance between high levels of reactive oxygen species (ROS) production and insufficient antioxidant defense resulting in lipid peroxidation, cellular membrane impairment, protein degradation, and DNA damage [1]. Excessive amounts of ROS induce neuronal cell death and are associated with neurodegenerative diseases, including Alzheimer’s disease (AD) [4]. According to the World Health Organization report in 2020, AD has affected millions of people and has become the leading cause of death worldwide [8]. In addition to this burden, current treatments are ineffective and unable to stop the progression of AD. Accumulating studies have confirmed that oxidative stress leads to the death of neuronal cells and is associated with the progression of neurodegenerative diseases, including Alzheimer’s disease (AD). Phytosterol is known to exhibit BBB penetration and exerts various bioactivities such as antioxidant and anticancer effects, and displays a potential treatment for dyslipidemia, cardiovascular disease, and dementia
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