Department of Pharmacology, Chongqing Medical University, The Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
Department of Pharmacology, Chongqing Medical University, The Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China; Pharmacy Department of GuiZhou Provincial People's Hospital, Guiyang 550000, China.
Free Radic Biol Med. 2019 Apr;134:239-247. doi: 10.1016/j.freeradbiomed.2019.01.019. Epub 2019 Jan 17.
This study was designed to investigate the neuroprotective effects of baicalein and the effect of the cortical 12/15-lipoxygenase (12/15-LOX) pathway on diabetic cognitive dysfunction. Our results showed that spatial learning and memory ability, as well as cortex neurons, were significantly impaired after the onset of diabetes. The fasting blood glucose and random blood glucose levels in the model group were significantly higher than those in the normal group. The levels of TG and TC in the plasma of the model group were significantly increased, but there was no significant difference in the LDL level. The insulin content in the plasma of diabetic rats was significantly lower than that of the normal group. The levels of inflammatory factors and 12(S)-HETE were significantly increased in diabetic rats, as were the protein expression levels of cPLA2, 12/15-LOX, p38MAPK, phospho-p38MAPK, caspase-3, caspase-9 and Aβ; by contrast, protein expression of Bcl-2 was significantly decreased. Administration of baicalein was shown to improve the spatial learning and memory ability and significantly decrease the levels of inflammatory cytokines. However, baicalein did not significantly influence the levels of blood glucose, lipids or insulin in rats. Baicalein treatment significantly protected diabetes rats from neuron death; significantly attenuated the overexpression of cPLA2, 12/15-LOX, p38MAPK, phospho-p38MAPK, caspase-3, caspase-9 and Aβ; and upregulated the expression of Bcl-2. These findings suggest that baicalein improves the cognitive function of diabetic rats by directly acting in the brain rather than by regulating the levels of blood glucose, lipids or insulin. In addition, baicalein can protect rat cortical neurons from damage caused by diabetes via inhibiting the 12/15-LOX pathway and relieving inflammation and apoptosis of the central nervous system.
本研究旨在探讨白杨素的神经保护作用及皮质 12/15-脂氧合酶（12/15-LOX）通路对糖尿病认知功能障碍的影响。我们的结果表明，糖尿病发病后，空间学习记忆能力和皮质神经元明显受损。模型组大鼠的空腹血糖和随机血糖水平明显高于正常组，血浆 TG 和 TC 水平明显升高，而 LDL 水平无明显差异。糖尿病大鼠血浆胰岛素含量明显低于正常组。糖尿病大鼠炎症因子和 12(S)-HETE 水平明显升高，cPLA2、12/15-LOX、p38MAPK、磷酸化 p38MAPK、caspase-3、caspase-9 和 Aβ 蛋白表达水平明显升高，Bcl-2 蛋白表达水平明显降低。白杨素给药可改善空间学习记忆能力，明显降低炎症因子水平，但对大鼠血糖、血脂和胰岛素水平无明显影响。白杨素治疗可显著减轻糖尿病大鼠神经元死亡，明显下调 cPLA2、12/15-LOX、p38MAPK、磷酸化 p38MAPK、caspase-3、caspase-9 和 Aβ 蛋白表达，上调 Bcl-2 蛋白表达。这些发现表明，白杨素通过直接作用于大脑而不是通过调节血糖、血脂或胰岛素水平来改善糖尿病大鼠的认知功能。此外，白杨素通过抑制 12/15-LOX 通路，减轻中枢神经系统炎症和细胞凋亡，可保护糖尿病大鼠皮质神经元免受损伤。
