Effects of gintonin-enriched fraction on hippocampal gene expressions

Abstract

Background Recently, gintonin and gintonin-enriched fraction (GEF) have been isolated from ginseng, a herbal medicine. Gintonin induces [Ca 2+ ] i transition in cultured hippocampal neurons and stimulates acetylcholine release through LPA receptor activation. Oral administration of GEF is linked to hippocampus-dependent cognitive enhancement and other neuroprotective effects; however, effects of its long-term administration on hippocampal gene expression remains unknown. Here, we used next-generation sequence (NGS) analysis to examine changes in hippocampal gene expressions after long-term oral administration of GEF. Methods C57BL/6 mice were divided into three groups: control group, GEF50 (GEF 50 mg/kg, p.o. ), and GEF100 (GEF 100 mg/kg, p.o. ). After 22 days, total RNA was extracted from mouse hippocampal tissues. NGS was used for gene expression profiling; quantitative-real-time PCR and western blot were performed to quantify the changes in specific genes and to confirm the protein expression levels in treatment groups. Results NGS analysis screened a total of 23,282 genes, analyzing 11-related categories. We focused on the neurogenesis category, which includes four genes for candidate markers: choline acetyltransferase (ChAT) gene, β 3 -adrenergic receptor (Adrb3) gene, and corticotrophin-releasing hormone (Crh) gene, and tryptophan 2,3-dioxygenase (Tdo2) gene. Real-time PCR showed a marked overexpression of ChAT, Adrb3, and Crh genes, while reduced expression of Tdo2. Western blot analysis also confirmed increased ChAT and decreased Tdo2 protein levels. Conclusion We found that GEF affects mouse hippocampal gene expressions, associated with memory, cognitive, anti-stress and anti-anxiety functions, and neurodegeneration at differential degree, that might explain the genetic bases of GEF-mediated neuroprotective effects.

Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway

“…Effects of gintonin on cell viability against iodoacetic acid (IAA)-mediated HT22 cell death. (A) IAA-induced cell death in a dose-dependent manner in HT22 cells treated with multiple concentrations of IAA (1,3,5,10,15, and 20 μM) for 2 h. (B) Dose-dependent effect of gintonin on cell viability against IAA-mediated cell apoptosis. After treating with 5 μM IAA for 2 h, HT22 cells were exposed to various concentrations of gintonin (0.1, 0.3, 1, 3, and 10 μg/mL) for 24 h. (C) Time-dependent effect of gintonin on cell viability against IAA-mediated cell apoptosis.…”

“…In previous in vivo studies, we demonstrated that oral administration of gintonin or gintonin-enriched fraction increased the expression of proteins involved in learning and memory and that of genes that affect cognitive function via anti-neurodegenerative activities [ 15 ]. However, relatively little is known about the neuroprotective effects of gintonin against oxidative stress in neuronal cells.…”

The Effects of Streptozotocin Induced Diabetes on the Hippocampus of Adult Male Albino Rats and the Possible Neuroprotective Role of Panax Ginseng

“…It also causes upregulation of Crh and Adrb3 genes which lower depression and anxietylike behavior in any stressful environment. Moreover, it causes downregulation of Tdo2 which is known to induce neurodegenerative effects [70] .…”

Choline Oxidase-Integrated Copper Metal–Organic Frameworks as Cascade Nanozymes for One-Step Colorimetric Choline Detection

“…Choline, as a precursor of acetylcholine, − has been identified as an essential nutrient for human health, with the main functions of transmitting nerve impulses and forming biofilms. − In addition, it also plays a crucial role in promoting brain development and improving memory. − Some diseases such as liver cirrhosis, atherosclerosis, Alzheimer’s disease, and growth disorder − may be induced by long-term lack of choline. Usually, food intake is the main way for the body to replenish choline, which makes the accurate determination of choline in foods a significant issue.…”