The glucotoxicity protecting effect of honokiol in human hepatocytes via directly activating AMPK.
The glucotoxicity protecting effect of honokiol in human hepatocytes via directly activating AMPK.
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DOI：
10.3389/fnut.2022.1043009
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发表时间：
2022
影响因子：
5
通讯作者：
Liu, Dongbo
中科院分区：
文献类型：
--
作者：
Liu, Hui;Luo, Wu;Liu, Jiazheng;Kang, Xincong;Yan, Jianming;Zhang, Tingting;Yang, Lan;Shen, Lu;Liu, Dongbo
持续的高血糖引起糖毒性，这被认为是2型糖尿病（T2D）及其代谢合并症中肝细胞损伤的一个因素。厚朴酚是一种天然的双酚类成分，来源于膳食补充剂厚朴提取物。本研究旨在探讨厚朴酚对肝细胞糖代谢紊乱和氧化应激的影响及其机制。以葡萄糖胺（18 mM）处理HepG2细胞诱导糖毒性，作为体外糖尿病并发症模型。在葡萄糖处理的HepG2细胞中，厚木酚显著增加葡萄糖消耗，增加2-NBDG摄取，促进GLUT2转运到质膜，表明厚木酚改善了葡萄糖代谢紊乱。此外，厚朴酚显著降低了葡萄糖胺诱导的ROS积累和线粒体膜电位的损失，表明厚朴酚减轻了葡萄糖毒性诱导的氧化应激。这些作用在很大程度上被化合物C（一种AMPK抑制剂）所消除，这表明厚朴酚在促进葡萄糖代谢和减轻氧化应激方面的功能依赖于AMPK的激活。分子对接结果表明，厚朴酚可与AMPK活性位点的氨基酸残基His151、Arg152、Lys243、Arg70、Lys170和His298相互作用。这些发现为厚朴酚的抗糖尿病作用提供了新的见解，厚朴酚可能是预防和治疗T2D及相关代谢合并症的有希望的药物。
Sustained hyperglycemia causes glucotoxicity, which has been regarded as a contributor to hepatocyte damage in type 2 diabetes (T2D) and its metabolic comorbidities. Honokiol is a natural biphenolic component derived from the dietary supplement Magnolia officinalis extract. This study aimed to investigate the effects of honokiol on glucose metabolism disorders and oxidative stress in hepatocytes and the underlying mechanisms. HepG2 cells were treated with glucosamines (18 mM) to induce glucotoxicity as a diabetic complication model in vitro. Honokiol significantly increased glucose consumption, elevated 2-NBDG uptake, and promoted GLUT2 translocation to the plasma membrane in glucosamine-treated HepG2 cells, indicating that honokiol ameliorates glucose metabolism disorders. Furthermore, glucosamine-induced ROS accumulation and loss of mitochondrial membrane potential were markedly reduced by honokiol, suggesting that honokiol alleviated glucotoxicity-induced oxidative stress. These effects were largely abolished by compound C, an AMPK inhibitor, suggesting an AMPK activation-dependent manner of honokiol function in promoting glucose metabolism and mitigating oxidative stress. Molecular docking results revealed that honokiol could interact with the amino acid residues (His151, Arg152, Lys243, Arg70, Lys170, and His298) in the active site of AMPK. These findings provide new insights into the antidiabetic effect of honokiol, which may be a promising agent for the prevention and treatment of T2D and associated metabolic comorbidities.
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DOI：
10.3390/antiox10122028
发表时间：
2021-12-20
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Hurtado-Carneiro V;Dongil P;Pérez-García A;Álvarez E;Sanz C
通讯作者：
Sanz C
影响因子：
7.7
作者：
Fujimoto, Yuka;Torres, Tracy P.;Shiota, Masakazu
通讯作者：
Shiota, Masakazu
DOI：
10.1152/ajpendo.00316.2005
发表时间：
2006-03-01
影响因子：
5.1
作者：
Kraegen, EW;Saha, AK;Ruderman, NB
通讯作者：
Ruderman, NB
影响因子：
5.6
作者：
Komarov, Gleb N.;Hope, Christopher K.;Higham, Susan M.
通讯作者：
Higham, Susan M.
影响因子：
5.6
作者：
Kim, Young-Je;Jung, Un Ju
通讯作者：
Jung, Un Ju