Punicalagin Attenuates Neuronal Apoptosis by Upregulating 5-Hydroxymethylcytosine in the Diabetic Mouse Brain
Punicalagin Attenuates Neuronal Apoptosis by Upregulating 5-Hydroxymethylcytosine in the Diabetic Mouse Brain
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DOI：
10.1021/acs.jafc.2c00863
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发表时间：
2022-04-27
影响因子：
6.1
通讯作者：
Li, Duo
中科院分区：
文献类型：
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作者：
He, Xin;Pei, Shengjie;Li, Duo
Punicalagin通过改善AMP激活的激酶（AMPK）和线粒体Krebs循环发挥神经保护活性。AMPK和Krebs循环代谢产物通过作用于10 - 11易位（泰特）酶来调节5-羟甲基胞嘧啶（5 hmC）。因此，我们假设安石榴苷通过上调糖尿病小鼠脑中的5 hmC来抑制糖尿病相关的神经元凋亡。将8周龄C57 BL/6 J小鼠随机分为正常对照组（NC）、糖尿病组（DM）、白藜芦醇组（RES）、安石榴苷低剂量组（LPU）和安石榴苷高剂量组（HPU），每组10只。与其他各组相比，DM组神经细胞凋亡率显著增高，大脑皮质5 hmC水平显著降低。DM组TET 2和P-AMPK α/AMPK α水平显著低于LPU组和HPU组。（琥珀酸+富马酸）/α-酮戊二酸的比值在DM组中显著高于其他组。本研究结果表明，安石榴苷上调5 hmC通过激活AMPK和维持Krebs循环稳态，从而抑制神经细胞凋亡在糖尿病小鼠脑。
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-AMPK alpha/AMPK alpha were significantly lower in the DM group than in both LPU and HPU groups. The ratio of (succinic acid + fumaric acid)/alpha-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.