Lin Chih-Hung, Wu Jiunn-Sheng, Hsieh Po-Chun, Chiu Valeria, Lan Chou-Chin, Kuo Chan-Yen
Department of Internal Medicine, Cathay General Hospital, Taipei 106, Taiwan.
School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan.
Evid Based Complement Alternat Med. 2022 Mar 16;2022:1072600. doi: 10.1155/2022/1072600. eCollection 2022.
Microglial cells are well-known phagocytic cells that are resistant to the central nervous system (CNS) and play an important role in the maintenance of CNS homeostasis. Activated microglial cells induce neuroinflammation under hypoxia and typically cause neuronal damage in CNS diseases. In this study, we propose that wild bitter melon extract (WBM) has a protective effect on hypoxia-induced cell death via regulation of ferroptosis, ER stress, and apoptosis. The results demonstrated that hypoxia caused microglial BV-2 the accumulation of lipid ROS, ferroptosis, ER stress, and apoptosis. In this study, we investigated the pharmacological effects of WBM on BV-2 cells following hypoxia-induced cell death. The results indicated that WBM reversed hypoxia-downregulated antiferroptotic molecules Gpx4 and SLC7A11, as well as upregulated the ER stress markers CHOP and Bip. Moreover, WBM alleviated hypoxia-induced apoptosis via the regulation of cleaved-caspase 3, Bax, and Bcl-2. Our results suggest that WBM may be a good candidate for preventing CNS disorders in the future.
小胶质细胞是众所周知的吞噬细胞，对中枢神经系统（CNS）具有抗性，并在维持CNS稳态中发挥重要作用。活化的小胶质细胞在缺氧情况下会诱发神经炎症，并且在CNS疾病中通常会导致神经元损伤。在本研究中，我们提出野生苦瓜提取物（WBM）通过调节铁死亡、内质网应激和细胞凋亡，对缺氧诱导的细胞死亡具有保护作用。结果表明，缺氧导致小胶质细胞BV-2中脂质活性氧的积累、铁死亡、内质网应激和细胞凋亡。在本研究中，我们研究了WBM对缺氧诱导细胞死亡后的BV-2细胞的药理作用。结果表明，WBM逆转了缺氧下调的抗铁死亡分子Gpx4和SLC7A11，同时上调了内质网应激标志物CHOP和Bip。此外，WBM通过调节裂解的半胱天冬酶3、Bax和Bcl-2减轻了缺氧诱导的细胞凋亡。我们的结果表明，WBM未来可能是预防CNS疾病的良好候选物。
