Department of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Xin'an Medicine (Anhui University of Chinese Medicine), Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230012, People's Republic of China.
Inflammopharmacology. 2023 Jun;31(3):1511-1527. doi: 10.1007/s10787-023-01201-4. Epub 2023 Mar 28.
The primary pathogenic factors of Alzheimer's disease (AD) have been identified as oxidative stress, inflammatory damage, and apoptosis. Chrysophanol (CHR) has a good neuroprotective effect on AD, however, the potential mechanism of CHR remains unclear.
In this study, we focused on the ROS/TXNIP/NLRP3 pathway to determine whether CHR regulates oxidative stress and neuroinflammation.
D-galactose and Aβ combination were used to build an in vivo model of AD, and the Y-maze test was used to evaluate the learning and memory function of rats. Morphological changes of neurons in the rat hippocampus were observed using hematoxylin and eosin (HE) staining. AD cell model was established by Aβ in PC12 cells. The DCFH-DA test identified reactive oxygen species (ROS). The apoptosis rate was determined using Hoechst33258 and flow cytometry. In addition, the levels of MDA, LDH, T-SOD, CAT, and GSH in serum, cell, and cell culture supernatant were detected by colorimetric method. The protein and mRNA expressions of the targets were detected by Western blot and RT-PCR. Finally, molecular docking was used to further verify the in vivo and in vitro experimental results.
CHR could significantly improve learning and memory impairment, reduce hippocampal neuron damage, and reduce ROS production and apoptosis in AD rats. CHR could improve the survival rate, and reduce the oxidative stress and apoptosis in the AD cell model. Moreover, CHR significantly decreased the levels of MDA and LDH, and increased the activities of T-SOD, CAT, and GSH in the AD model. Mechanically, CHR significantly reduced the protein and mRNA expression of TXNIP, NLRP3, Caspase-1, IL-1β, and IL-18, and increase TRX.
CHR exerts neuroprotective effects on the Aβ-induced AD model mainly by reducing oxidative stress and neuroinflammation, and the mechanism may be related to ROS/TXNIP/NLRP3 signaling pathway.
阿尔茨海默病（AD）的主要致病因素已被确定为氧化应激、炎症损伤和细胞凋亡。大黄素（CHR）对 AD 具有良好的神经保护作用，但 CHR 的潜在机制尚不清楚。
本研究聚焦于 ROS/TXNIP/NLRP3 通路，以确定 CHR 是否调节氧化应激和神经炎症。
采用 D-半乳糖和 Aβ 联合建立 AD 体内模型，采用 Y 迷宫试验评价大鼠学习记忆功能。采用苏木精和伊红（HE）染色观察大鼠海马神经元形态变化。采用 Aβ 在 PC12 细胞中建立 AD 细胞模型。采用 DCFH-DA 试验鉴定活性氧（ROS）。采用 Hoechst33258 和流式细胞术检测细胞凋亡率。此外，采用比色法检测血清、细胞和细胞培养上清液中 MDA、LDH、T-SOD、CAT 和 GSH 的水平。采用 Western blot 和 RT-PCR 检测靶蛋白和 mRNA 的表达。最后，采用分子对接进一步验证体内和体外实验结果。
CHR 可显著改善 AD 大鼠学习记忆障碍，减轻海马神经元损伤，降低 AD 大鼠 ROS 产生和细胞凋亡。CHR 可提高 AD 细胞模型的存活率，降低氧化应激和细胞凋亡。此外，CHR 显著降低 AD 模型 MDA 和 LDH 水平，提高 T-SOD、CAT 和 GSH 活性。机制上，CHR 显著降低 TXNIP、NLRP3、Caspase-1、IL-1β和 IL-18 的蛋白和 mRNA 表达，增加 TRX。
CHR 对 Aβ 诱导的 AD 模型发挥神经保护作用，主要通过降低氧化应激和神经炎症，其机制可能与 ROS/TXNIP/NLRP3 信号通路有关。
