Mangiferin and Morin Attenuate Oxidative Stress, Mitochondrial Dysfunction, and Neurocytotoxicity, Induced by Amyloid
Elena Alberdi1,2,3, María Victoria Sánchez-Gómez1,2,3, Asier Ruiz1,2,3
1Departamento de Neurociencias, Universidad del País Vasco (UPV/EHU), 48940 Leioa, Spain.
Abstract:
Amyloid beta- (Aβ-) mediated ROS overproduction disrupts intraneuronal redox balance and exacerbates mitochondrial dysfunction which leads to neuronal injury. Polyphenols have been investigated as therapeutic agents that promote neuroprotective effects in experimental models of brain injury and neurodegenerative diseases. The aim of this study was to identify the neuroprotective effects of morin and mangiferin against Aβ oligomers in cultured cortical neurons and organotypic slices as well as their mechanisms of action. Cell death caused by Aβ oligomers in neuronal cultures was decreased in the presence of micromolar concentrations of mangiferin or morin, which in turn attenuated oxidative stress. The neuroprotective effects of antioxidants against Aβ were associated with the reduction of Aβ-induced calcium load to mitochondria; mitochondrial membrane depolarization; and release of cytochrome c from mitochondria, a key trigger of apoptosis. Additionally, we observed that both polyphenols activated the endogenous enzymatic antioxidant system and restored oxidized protein levels. Finally, Aβ induced an impairment of energy homeostasis due to a decreased respiratory capacity that was mitigated by morin and mangiferin. Overall, the beneficial effects of polyphenols in preventing mitochondrial dysfunction and neuronal injury in AD cell models suggest that morin and mangiferin hold promise for the treatment of this neurological disorder.
Insights
Morin and mangiferin, natural polyphenols, protect neurons from amyloid beta toxicity by reducing oxidative stress and improving mitochondrial function. These compounds show promise for treating Alzheimer's disease (AD) by preserving neuronal integrity.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Amyloid beta (Aβ) oligomers induce oxidative stress and mitochondrial dysfunction, leading to neuronal injury relevant to Alzheimer's disease (AD).
- Polyphenols are explored for neuroprotective properties against brain injury and neurodegenerative conditions.
Purpose of the Study:
- To investigate the neuroprotective effects of morin and mangiferin against Aβ oligomers in neuronal models.
- To elucidate the underlying mechanisms of action for morin and mangiferin's neuroprotection.
Main Methods:
- Utilized cultured cortical neurons and organotypic slices exposed to Aβ oligomers.
- Assessed cell viability, oxidative stress markers, mitochondrial function (calcium load, membrane potential, cytochrome c release), antioxidant enzyme activity, and respiratory capacity.
- Evaluated the impact of morin and mangiferin on these parameters.
Main Results:
- Morin and mangiferin significantly reduced Aβ oligomer-induced neuronal cell death and attenuated oxidative stress.
- Neuroprotection was linked to reduced mitochondrial calcium overload, preserved mitochondrial membrane potential, and inhibited cytochrome c release.
- Both polyphenols enhanced endogenous antioxidant systems, restored oxidized proteins, and mitigated Aβ-induced impairment of respiratory capacity and energy homeostasis.
Conclusions:
- Morin and mangiferin demonstrate significant neuroprotective effects against Aβ oligomer toxicity in neuronal cell models.
- These polyphenols counteract Aβ-induced mitochondrial dysfunction and oxidative stress through multiple mechanisms.
- Morin and mangiferin show therapeutic potential for Alzheimer's disease treatment by preserving neuronal health and mitochondrial function.
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