Yang Youxi, Shi Liying, Xu Xiaoting, Luo Bilan, Cui Xing, Tang Lei, Wang Jianta
Guizhou Provincial Engineering Technology Researcch Center for Chemical Drug R&D, College of Pharmacy, Guizhou Medical University, Guiyang 561113, China.
Department of Ultrasound, The Affiliated Hospital of Guizhou Medical University, Guiyang 550025, China.
Korean J Physiol Pharmacol. 2025 Sep 1;29(5):547-557. doi: 10.4196/kjpp.24.304. Epub 2025 May 15.
Ischemic stroke is a leading cause of death and disability worldwide. Amorfrutin A (AA), a small molecule compound found in L. (bastard indigo), possesses various activities, including blood glucose regulation, antiinflammatory, analgesic, and tumor suppression. In this study, we used the middle cerebral artery occlusion/reperfusion (MCAO/R) model and the oxygen glucose deprivation/ reoxygenation (OGD/R) model to mimic the ischemia/reperfusion process and , respectively. The role of AA in ischemic stroke was evaluated by CCK-8 assay, ELISA, TTC staining, hematoxylin-eosin staining and Western blot assay. AA increased the survival of BV2 or PC12 cells following OGD/R injury. Meanwhile, AA effectively suppressed the release of reactive oxygen species, nitric oxide, and tumor necrosis factor-α (TNF-α) in BV2 or PC12 cells subjected to OGD/R. After 24 h of MCAO/R surgery, AA significantly reduced the neurological deficit score, diminished the cerebral infarct volume, and attenuated brain pathological injury in rats. AA administration significantly increased superoxide dismutase and glutathione peroxidase levels, reduced malondialdehyde production, and inhibited the release of inflammatory cytokines interleukin-1β and TNF-α in the ischemic brain tissue of MCAO/R rats. In addition, AA suppressed Kelch-like ECH-associated protein 1 expression and promoted nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1, and heme oxygenase 1 (HO-1) expression in rat ischemic brain. AA may be a potential drug for the treatment of ischemic stroke. Its antioxidant and anti-inflammatory effects in cerebral ischemia-reperfusion injury may be related to Nrf2/HO-1 signaling pathway.
缺血性中风是全球范围内导致死亡和残疾的主要原因。阿莫弗鲁汀A（AA）是一种在野青树中发现的小分子化合物，具有多种活性，包括血糖调节、抗炎、镇痛和肿瘤抑制作用。在本研究中，我们分别使用大脑中动脉闭塞/再灌注（MCAO/R）模型和氧糖剥夺/复氧（OGD/R）模型来模拟缺血/再灌注过程。通过CCK-8测定、ELISA、TTC染色、苏木精-伊红染色和蛋白质印迹分析评估了AA在缺血性中风中的作用。AA增加了OGD/R损伤后BV2或PC12细胞的存活率。同时，AA有效抑制了OGD/R处理的BV2或PC12细胞中活性氧、一氧化氮和肿瘤坏死因子-α（TNF-α）的释放。MCAO/R手术24小时后，AA显著降低了大鼠的神经功能缺损评分，减小了脑梗死体积，并减轻了脑病理损伤。给予AA可显著提高超氧化物歧化酶和谷胱甘肽过氧化物酶水平，降低丙二醛生成，并抑制MCAO/R大鼠缺血脑组织中炎性细胞因子白细胞介素-1β和TNF-α的释放。此外，AA抑制了大鼠缺血脑中类Kelch样ECH相关蛋白1的表达，并促进了核因子红细胞2相关因子2（Nrf2）、NAD（P）H醌氧化还原酶1和血红素加氧酶1（HO-1）的表达。AA可能是一种治疗缺血性中风的潜在药物。其在脑缺血再灌注损伤中的抗氧化和抗炎作用可能与Nrf2/HO-1信号通路有关。
