School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Food Funct. 2021 Sep 7;12(17):8056-8067. doi: 10.1039/d1fo01144h. Epub 2021 Jul 20.
Ischemic stroke (IS) caused by cerebral arterial occlusion is the leading cause of global morbidity and mortality. Cellular oxidative stress and inflammation play a vital role in the pathological process of neural damage in IS. It is necessary to develop functional food or drugs, which target neuroinflammation and oxidation mechanisms against IS. The molecule compound aloe-emodin (AE) is derived from aloe and rhubarb. However, the exact mechanism of the pharmacological action of AE on IS remains unclear. Here, for aiming to demonstrate the mechanism of AE, our study explored the middle cerebral occlusion reperfusion (MCAO/R) rats in vivo, oxygen and glucose deprivation reperfusion (OGD/R), and lipopolysaccharide (LPS)-stimulated cells in vitro. We found that AE significantly improved the infarct size and behavioral score of MCAO/R rats, decreased the expression of TNF-α, MDA, LDH, Caspase 3, and increased the expression of SOD, Bcl-2/Bax. Liquid chromatography-mass spectrometry (LC/MS) results showed that AE could penetrate the blood-brain barrier in the sham group and MCAO/R group. In vitro, AE significantly protected SH-SY5Y cells from the insult of OGD/R and reduced the production of inflammatory cytokines in BV2 cells stimulated by LPS. In vivo and in vitro, western blot analysis results showed that AE significantly increased the expression of PI3K, AKT and mTOR proteins. In addition, AE significantly decreased NF-κB protein expression in BV2 cells. The use of AKT-specific inhibitor MK-2206 2HCL to inhibit AKT expression can block the protective effect of AE on SH-SY5Y cells subjected to OGD/R insults. Overall, our study suggests that AE protected against cerebral ischemia-reperfusion injury probably via the PI3K/AKT/mTOR and NF-κB signaling pathways. Thus, these results indicated that AE could be a promising first-line therapy for preventing and treating ischemic stroke and can be used as functional food.
缺血性脑卒中（IS）是由脑动脉闭塞引起的，是导致全球发病率和死亡率的主要原因。细胞氧化应激和炎症在 IS 引起的神经损伤的病理过程中起着至关重要的作用。因此，有必要开发针对 IS 的神经炎症和氧化机制的功能性食品或药物。分子化合物大黄素（AE）来源于芦荟和大黄。然而，AE 对 IS 的药理作用的确切机制尚不清楚。在这里，为了阐明 AE 的作用机制，我们在体内研究了大脑中动脉闭塞再灌注（MCAO/R）大鼠、氧葡萄糖剥夺再灌注（OGD/R）和脂多糖（LPS）刺激的细胞，在体外。我们发现 AE 显著改善了 MCAO/R 大鼠的梗死面积和行为评分，降低了 TNF-α、MDA、LDH、Caspase 3 的表达，增加了 SOD、Bcl-2/Bax 的表达。液相色谱-质谱（LC/MS）结果表明，AE 可以穿透假手术组和 MCAO/R 组大鼠的血脑屏障。在体外，AE 显著保护 SH-SY5Y 细胞免受 OGD/R 的损伤，并降低 LPS 刺激的 BV2 细胞中炎症细胞因子的产生。在体内和体外，Western blot 分析结果表明，AE 显著增加了 PI3K、AKT 和 mTOR 蛋白的表达。此外，AE 显著降低了 LPS 刺激的 BV2 细胞中 NF-κB 蛋白的表达。使用 AKT 特异性抑制剂 MK-2206 2HCL 抑制 AKT 表达可以阻断 AE 对 OGD/R 损伤的 SH-SY5Y 细胞的保护作用。总的来说，我们的研究表明，AE 通过 PI3K/AKT/mTOR 和 NF-κB 信号通路来保护脑缺血再灌注损伤。因此，这些结果表明，AE 可能是预防和治疗缺血性中风的一种有前途的一线治疗药物，并可作为功能性食品。
