Punicalagin Attenuates Neuronal Apoptosis by Upregulating 5-Hydroxymethylcytosine in the Diabetic Mouse Brain

Abstract

Punicalagin exerts neuroprotective activity by improving AMP-activated kinase (AMPK) and mitochondrial Krebs cycle. AMPK and Krebs cycle metabolites regulate 5-hydroxymethylcytosine (5hmC) via acting on ten-eleven translocation (TET) enzymes. Therefore, we hypothesized that punicalagin inhibits diabetes-related neuronal apoptosis by upregulating 5hmC in the diabetic mouse brain. C57BL/6J mice aged 8 weeks were randomly separated into five groups (n = 10), normal control (NC), diabetes mellitus (DM), resveratrol (RES), low-dose punicalagin (LPU), and high-dose punicalagin (HPU). Compared with other groups, the neuronal apoptosis rate was significantly higher and the 5hmC level of the cerebral cortex was significantly lower in the DM group. The levels of TET2 and P-AMPKα/AMPKα were significantly lower in the DM group than in both LPU and HPU groups. The ratio of (succinic acid + fumaric acid)/α-ketoglutarate was significantly higher in the DM group than in other groups. The present results suggest that punicalagin upregulates 5hmC via activating AMPK and maintaining Krebs cycle homeostasis, thus inhibiting neuronal apoptosis in the diabetic mouse brain.

Protective effects of apple polyphenols on bone loss in mice with high fat diet-induced obesity

“…The method of sodium dodecyl sulfate–polyacrylamide gel electrophoresis was adopted with reference to our previous study. 21 The primary antibodies included rabbit anti-RANKL (YT5404, 1 : 1000, Immunoway, China), rabbit anti-osteoprotegerin (OPG, ab183910, 1 : 500, Abcam, UK), rabbit anti-Runx2 (ab92336, 1 : 500, Abcam, UK), and mouse anti-GAPDH (BM1623, 1 : 1000, Boster, China). The protein expression levels were determined using ImageJ software (version 1.53 K, USA), and the data were normalized to 1.…”

Microbiota from Exercise Mice Counteracts High-Fat High-Cholesterol Diet-Induced Cognitive Impairment in C57BL/6 Mice

“…Metabolites by GC-MS. Gas chromatography-mass spectrometry (GC-MS) was used to analyze the Krebs cycle intermediate metabolites as described previously by He et al [18]. The cerebral cortex was weighed and ground with liquid nitrogen and 10 times the volume of extraction buffer (methanol: chloroform: water = 2 : 5 : 2) was added and vortexed vigorously for 15 seconds.…”

Thinned young apple polyphenols may prevent neuronal apoptosis by up-regulating 5-hydroxymethylcytosine in the cerebral cortex of high-fat diet-induced diabetic mice

“…The treatment amount was chosen based on previous in vivo studies and our preliminary test, and this dose has been proven to be effective and non-toxic. 10,20,21 In addition, the Con group was fed with a standard diet (D12450J, 10% kcal from fat, 70% kcal from carbohydrate, and 20% kcal from protein, Research Diets Inc., New Brunswick, NJ, USA) and received a daily gavage of the same volume of saline. Other groups were fed with a high-fat diet (D12492, 60% kcal from fat, 20% kcal from carbohydrate and 20% kcal from protein, Research Diets Inc., New Brunswick, NJ, USA) for 8 weeks.…”

“…8,9 Our previous studies have shown that there is an abnormal decrease of 5hmC in neurons during diabetes-induced neuronal apoptosis, and the downregulation of 5hmC has significant impacts on tricarboxylic acid (TCA) cycle homeostasis and AMPK function. 3,10 Thinning young apples is an effective measure to improve the quality of apples at harvest and to balance the yield of apples during the following year. It is well known that thinned young apples represent a rich source of natural apple polyphe-nols.…”