Mangiferin and Morin Attenuate Oxidative Stress, Mitochondrial Dysfunction, and Neurocytotoxicity, Induced by Amyloid Beta Oligomers

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.

Early Effects of Aβ Oligomers on Dendritic Spine Dynamics and Arborization in Hippocampal Neurons

“…Here, we analyzed spine dynamics, i.e., change in spine shapes and the appearance or loss of spines over time in living cell cultures. Accordingly, we observed that soluble forms of Aβ peptide or Aβ oligomers, as the active components (Alberdi et al, 2018), modulated spine dynamics within a very short-term time window. Overall, most dendritic spines were highly stable under basal conditions, whereas after treatment with Aβ oligomer stubby and mushroom spines showed the most dynamic the most dynamic behavior.…”

“…Soluble oligomeric Aβ 1-42 was prepared as reported previously (Dahlgren et al, 2002;Alberdi et al, 2010Alberdi et al, , 2018. Briefly, Aβ 1-42 (Bachem, Bubendorf, Switzerland) was initially dissolved to 1 mM in hexafluoroisopropanol (Sigma-Aldrich, Saint Louis, MO, USA) and distributed into aliquots in sterile microcentrifuge tubes.…”

Aqueous Extract of Davallia mariesii Attenuates 6-Hydroxydopamine-Induced Oxidative Damage and Apoptosis in B35 Cells Through Inhibition of Caspase Cascade and Activation of PI3K/AKT/GSK-3β Pathway

“…Many studies have evidenced that both phytoconstituents of DM extract, mangiferin and epicatechin, possessed neuroprotective and antiapoptotic effects in vitro and in vivo. Mangiferin protected against oxidative stress, mitochondrial dysfunction, and apoptosis caused by 6-OHDA, rotenone, MPTP, amyloid beta oligomers and subarachnoid hemorrhage [ 28 , 29 , 30 , 31 , 32 ]. Epicatechin also had neuroprotective effects against 6-OHDA-induced striatal or amyloid 25-35-induced hippocampal oxidative stress [ 33 , 34 ].…”

The Protective Effect of DiDang Tang Against AlCl3-Induced Oxidative Stress and Apoptosis in PC12 Cells Through the Activation of SIRT1-Mediated Akt/Nrf2/HO-1 Pathway

“…Oxidative stress and mitochondrial apoptosis have long been implicated in a variety of neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), and stroke (Zhang J. et al, 2017;Alberdi et al, 2018;Dai et al, 2018). The mechanism underlying aluminum neurotoxicity is poorly understood, but damage to the mitochondria and production of ROS are considered key contributors to aluminuminduced neurodegenerative disease (Leuner et al, 2007).…”