Lee Hyun-Su, Jeong Gil-Saeng
College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Korea.
Antioxidants (Basel). 2021 Feb 24;10(3):341. doi: 10.3390/antiox10030341.
Since hypoxia-induced neurotoxicity is one of the major causes of neurodegenerative disorders, including the Alzheimer's disease, continuous efforts to find a novel antioxidant from natural products are required for public health. 6,7,4'-trihydroxyflavanone (THF), isolated from , has been shown to inhibit osteoclast formation and have an antibacterial activity. However, no evidence has reported whether THF has a protective role against hypoxia-induced neurotoxicity. In this study, we found that THF is not cytotoxic, but pre-treatment with THF has a cytoprotective effect on CoCl-induced hypoxia by restoring the expression of anti-apoptotic proteins in SH-SY5y cells. In addition, pre-treatment with THF suppressed CoCl-induced hypoxia-related genes including , , , and at the mRNA and protein levels. Pre-treatment with THF also attenuated the oxidative stress occurred by CoCl-induced hypoxia by preserving antioxidant proteins, including SOD and CAT. We revealed that treatment with THF promotes HO-1 expression through Nrf2 nuclear translocation. An inhibitor assay using tin protoporphyrin IX (SnPP) confirmed that the enhancement of HO-1 by pre-treatment with THF protects SH-SY5y cells from CoCl-induced neurotoxicity under hypoxic conditions. Our results demonstrate the advantageous effects of THF against hypoxia-induced neurotoxicity through the HO-1/Nrf2 signaling pathway and provide a therapeutic insight for neurodegenerative disorders.
由于缺氧诱导的神经毒性是包括阿尔茨海默病在内的神经退行性疾病的主要原因之一，因此为了公众健康，需要持续努力从天然产物中寻找新型抗氧化剂。从[具体来源未给出]中分离出的6,7,4'-三羟基黄烷酮（THF）已被证明能抑制破骨细胞形成并具有抗菌活性。然而，尚无证据报道THF是否对缺氧诱导的神经毒性具有保护作用。在本研究中，我们发现THF无细胞毒性，但预先用THF处理可通过恢复SH-SY5y细胞中抗凋亡蛋白的表达对氯化钴诱导的缺氧产生细胞保护作用。此外，预先用THF处理在mRNA和蛋白质水平上抑制了氯化钴诱导的包括[相关基因未明确列出]等缺氧相关基因。预先用THF处理还通过保留包括超氧化物歧化酶（SOD）和过氧化氢酶（CAT）在内的抗氧化蛋白减轻了氯化钴诱导的缺氧所产生的氧化应激。我们发现用THF处理可通过Nrf-核转位促进血红素加氧酶-1（HO-1）的表达。使用锡原卟啉IX（SnPP）的抑制剂试验证实，预先用THF处理增强HO-1可在缺氧条件下保护SH-SY5y细胞免受氯化钴诱导的神经毒性。我们的结果证明了THF通过HO-1/Nrf2信号通路对缺氧诱导的神经毒性具有有益作用，并为神经退行性疾病提供了治疗思路。
