Procyanidins Extracted from Lotus Seedpod Ameliorate Amyloid‐β‐Induced Toxicity in Rat Pheochromocytoma Cells

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease, which is characterized by extracellular senile plaque deposits, intracellular neurofibrillary tangles, and neuronal apoptosis. Amyloid-β (Aβ) plays a critical role in AD that may cause oxidative stress and downregulation of CREB/BDNF signaling. Anti-Aβ effect has been discussed as a potential therapeutic strategy for AD. This study aimed to identify the amelioration of procyanidins extracted from lotus seedpod (LSPC) on Aβ-induced damage with associated pathways for AD treatment. Rat pheochromocytoma (PC12) cells incubated with Aβ 25–35 serve as an Aβ damage model to evaluate the effect of LSPC in vitro. Our findings illustrated that LSPC maintained the cellular morphology from deformation and reduced apoptosis rates of cells induced by Aβ 25–35. The mechanisms of LSPC to protect cells from Aβ-induced damage were based on its regulation of oxidation index and activation of CREB/BDNF signaling, including brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP-responsive element-binding (CREB), protein kinase B (also known as AKT), and the extracellular signal-regulated kinase (ERK). Of note, by high-performance liquid chromatography-tandem mass spectroscopy (LC-MS/MS), several metabolites were detected to accumulate in vivo, part of which could take primary responsibility for the amelioration of Aβ-induced damage on PC12 cells. Taken together, our research elucidated the effect of LSPC on neuroprotection through anti-Aβ, indicating it as a potential pretreatment for Alzheimer's disease.

Quercetin‐3‐O‐Glucuronide Alleviates Cognitive Deficit and Toxicity in Aβ1‐42‐Induced AD‐Like Mice and SH‐SY5Y Cells

“…Meanwhile, a significant decrease in the abilities of spatial learning and memory was observed through MWM test in Aβ‐induced mice, while Q3G administration improved memory. Consistent with our previous study, [ 31 ] we also observed supplement with Q3G restored hippocampal CREB activity and BDNF levels, which were pivoted in the synaptic plasticity and tightly related with memory developing. [ 49 ] Taken together, our findings indicated that Q3G might ameliorate cognitive impairment and trigger a beneficial effect on synaptic plasticity.…”

“…[28,29] In our previous study, LSPC exhibited the improvement of cognitive dysfunction and memory loss in the aged rats [30] and anti-A toxicity effects of LSPC on rat pheochromocytoma cells. [31] Through LC-MS/MS, we found that quercetin-3-O-glucuronide (Q3G) in LSPC was a primary metabolite in the brain. Quercetin was proved the effects of anti-Alzheimer, anti-diabetic, and anti-obesity.…”

SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases

“…Procyanidins upregulate the SIRT1 that stimulates CREB (cAMP response element-binding), which acts as a molecular switch from short to long term memory ( Zhao et al, 2019 ). A new investigation has illustrated that procyanidins maintain cellular morphology and protect it from deformation and decrease apoptosis rates in PC12 cells induced by Aβ 25–35 ( Huang et al, 2018 ).…”

Organ-differential Roles of Akt/FoxOs Axis as a Key Metabolic Modulator during Aging

“…FoxO1 promotes glucose production in the liver along with the conversion of carbohydrate oxidation to lipid oxidation in fasting muscle [ 30 ]. In the fasting state, hepatic FoxOs [ 31 ] are activated owing to the decrease in Akt levels [ 32 ]. FoxOs mediates glucose metabolism by converting glucose to acetate for oxidation or to fatty acids [ 33 ].…”

“…We previously reported that Akt-induced FoxO1 phosphorylation was reduced in the livers of aged rats, whereas it was increased in the kidney [ 65 ]. Different trends of changes in the Akt/FoxOs axis in metabolic and non-metabolic organs during aging are shown in Table 1 [ 31 , 32 , 60 - 62 , 66 - 73 ].…”