DPHC From Alpinia officinarum Ameliorates Oxidative Stress and Insulin Resistance via Activation of Nrf2/ARE Pathway in db/db Mice and High Glucose-Treated HepG2 Cells.
DPHC From Alpinia officinarum Ameliorates Oxidative Stress and Insulin Resistance via Activation of Nrf2/ARE Pathway in db/db Mice and High Glucose-Treated HepG2 Cells.
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DOI：
10.3389/fphar.2021.792977
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发表时间：
2021
影响因子：
5.6
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Zhang X;Zhang Y;Zhou M;Xie Y;Dong X;Bai F;Zhang J
（R）-5-羟基-1，7-二苯基-3-庚酮（DPHC）是从天然植物高良姜（Alpinia officinarum）中提取的一种具有抗氧化和抗糖尿病作用的化合物。本研究从体内外氧化应激和胰岛素抵抗（IR）的调节方面，探讨DPHC对2型糖尿病（T2 DM）的治疗作用及其分子机制。在体内，DPHC治疗8周后，db/db小鼠的空腹血糖（FBG）水平显著降低，葡萄糖耐量和胰岛素敏感性改善。在体外实验中，DPHC通过增加高糖诱导的IR-HepG 2细胞对葡萄糖的消耗和摄取，改善IR。此外，体内外实验表明，DPHC可调节超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）等抗氧化酶水平，从而减少氧化应激的发生，改善胰岛素抵抗。Western blotting和聚合酶链反应结果显示，DPHC可促进核因子红细胞2相关因子2（Nrf 2）、血红素加氧酶-1（HO-1）、蛋白激酶B（AKT）和葡萄糖转运蛋白4（GLUT 4）的表达，降低c-Jun N-末端激酶（JNK）和胰岛素受体底物-1（IRS-1）在Ser 307上的磷酸化水平。这些结果证实DPHC具有通过激活db/db小鼠和IR-HepG 2细胞的Nrf 2/ARE信号通路来减轻氧化应激和IR从而治疗T2 DM的潜力。
(R)-5-hydroxy-1,7-diphenyl-3-heptanone (DPHC) from the natural plant Alpinia officinarum has been reported to have antioxidation and antidiabetic effects. In this study, the therapeutic effect and molecular mechanism of DPHC on type 2 diabetes mellitus (T2DM) were investigated based on the regulation of oxidative stress and insulin resistance (IR) in vivo and in vitro. In vivo, the fasting blood glucose (FBG) level of db/db mice was significantly reduced with improved glucose tolerance and insulin sensitivity after 8 weeks of treatment with DPHC. In vitro, DPHC ameliorated IR because of its increasing glucose consumption and glucose uptake of IR-HepG2 cells induced by high glucose. In addition, in vitro and in vivo experiments showed that DPHC could regulate the antioxidant enzyme levels including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby reducing the occurrence of oxidative stress and improving insulin resistance. Western blotting and polymerase chain reaction results showed that DPHC could promote the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), the heme oxygenase-1 (HO-1), protein kinase B (AKT), and glucose transporter type 4 (GLUT4), and reduced the phosphorylation levels of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) on Ser307 both in vivo and in vitro. These findings verified that DPHC has the potential to relieve oxidative stress and IR to cure T2DM by activating Nrf2/ARE signaling pathway in db/db mice and IR-HepG2 cells.
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影响因子：
--
作者：
Maiese K
通讯作者：
Maiese K
影响因子：
4.8
作者：
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DOI：
10.1124/jpet.109.162271
发表时间：
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影响因子：
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DOI：
10.1124/jpet.105.093831
发表时间：
2006-02-01
影响因子：
3.5
作者：
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通讯作者：
Stulnig, TM
影响因子：
3.4
作者：
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