Work

Thinned young apple polyphenol mitigates palmitic acid-induced neuronal injury by upregulating TET2 in primary hippocampal neurons

Year: 2025

Type: article

Abstract: Purpose Thinned young apple polyphenol (TYAP) has demonstrated neuroprotective effects, likely by enhancing mitochondrial function through the involvement of 5-hydroxymethylcytosine (5hmC) levels and the ten-eleven translocation (TET) enzymes . This study aimed to evaluate whether TYAP restores mitochondrial function and 5hmC levels in a palmitic acid (PAL)-induced hippocampal injury model. Approach Palmitic acid (PAL)-induced hippocampal injury was prepared in primary hippocampal neurons, and the TYAP treatments with different doses (50–200 μg/mL) were also applied. The neurons were randomly assigned to 6 groups: Control, Control + TYAP (200 μg/mL), PAL, PAL + TYAP (50 μg/mL), PAL + TYAP (100 μg/mL), and PAL + TYAP (200 μg/mL). Outcomes, including measures of inflammation, oxidative stress , apoptosis, mitochondrial function, and DNA epigenetic changes (such as 5hmC and 5 mC), were assessed. Additionally, the effects of TYAP were evaluated in TET2-knockdown HT22 cells to assess the involvement of TET2 in TYAP treatment. Results TYAP mitigated PAL-induced hippocampal injury by restoring TET2 and 5hmC levels, reducing oxidative stress , inflammation, and apoptosis, and enhancing mitochondrial function. Knockdown of TET2 abolished these effects, demonstrating the critical role of TET2 in TYAP-mediated neuroprotection . Conclusions TYAP confers neuroprotection against PAL-induced hippocampal neuron damage through the TET2-5hmC pathway, highlighting its potential as a therapeutic agent for neurological conditions associated with mitochondrial dysfunction and apoptosis.

Source: Journal of Agriculture and Food Research

DOI: 10.1016/j.jafr.2025.101694