Tang Hongxing, He Kejun, Zhao Kun, Zheng Chen, Wu Weichi, Jin Weilin, Yang Lixuan, Xie Baoshu
Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou, China.
J Neurotrauma. 2024 Mar;41(5-6):734-750. doi: 10.1089/neu.2023.0150. Epub 2023 Dec 28.
In this study, we investigated the effects of hinokitiol, a small-molecule natural compound, against neuronal ferroptosis after traumatic brain injury (TBI). A controlled cortical impact (CCI) mouse model and excess glutamate-treated HT-22 cells were used to study the effects of hinokitiol on TBI. Hinokitiol mitigated TBI brain tissue lesions and significantly improved neurological function. Neuron loss and iron deposition were ameliorated after hinokitiol administration. Hinokitiol alleviated excessive glutamate-induced intracellular reactive oxygen species (ROS), lipid peroxidation, and Fe accumulation in HT-22. Mechanistically, hinokitiol upregulated heme oxygenase-1 (HO-1) expression, promoted nuclear factor-erythroid factor 2-related factor 2 (Nrf2) nuclear translocation, and inhibited the activation of microglia and astrocyte after TBI. These results suggest that hinokitiol has neuroprotective effects on rescuing cells from TBI-induced neuronal ferroptosis. In summary, hinokitiol is a potential therapeutic candidate for TBI by activating the Nrf2/Keap1/HO-1 signaling pathway.
在本研究中，我们探究了小分子天然化合物扁柏酚对创伤性脑损伤（TBI）后神经元铁死亡的影响。采用控制性皮质撞击（CCI）小鼠模型和经过量谷氨酸处理的HT-22细胞来研究扁柏酚对TBI的影响。扁柏酚减轻了TBI脑组织损伤并显著改善了神经功能。给予扁柏酚后，神经元丢失和铁沉积得到改善。扁柏酚减轻了过量谷氨酸诱导的HT-22细胞内活性氧（ROS）生成、脂质过氧化及铁蓄积。机制上，扁柏酚上调了血红素加氧酶-1（HO-1）表达，促进了核因子红细胞2相关因子2（Nrf2）核转位，并抑制了TBI后小胶质细胞和星形胶质细胞的激活。这些结果表明，扁柏酚对挽救TBI诱导的神经元铁死亡中的细胞具有神经保护作用。总之，扁柏酚通过激活Nrf2/Keap1/HO-1信号通路，是TBI潜在的治疗候选物。
