a Department of Neurology , China-Japan Union Hospital of Jilin University , Changchun , China.
b Department of Spine Surgery , The Second Hospital of Jilin University , Changchun , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1653-1661. doi: 10.1080/21691401.2019.1606010.
Finding novel therapeutic agent for the treatment of cerebral ischemia is urgently required. These experiments explored the potential roles of 6-Gingerols (6G) in hypoxia-stimulated rat PC-12 cells. Cell viability, apoptosis and its related proteins were studied by the approaches of MTT assay, flow cytometry assay and Western blot analysis, respectively. In addition, whether 6G achieved its functions in hypoxia-induced injury through miR-103 was illustrated. Moreover, the associated signalling pathways were investigated. Obviously, hypoxia treatment blocked cell viability and enhanced apoptosis while this trend was ameliorated by 6G. Then we observed that hypoxia administration up-regulated miR-103 expression and 6G could further increase miR-103 expression in hypoxia-stimulated PC-12 cells. Inhibition of miR-103 attenuated the neuroprotective effects of 6G on hypoxia-treated PC-12 cells. Moreover, Bcl2/adenovirus EIB 19kD-interacting protein 3 (BNIP3) was a target of miR-103 and BNIP3 upregulation also attenuated the neuroprotective impact of 6G on hypoxia-treated PC-12 cells. Hypoxia activated the p38MAPK and JNK pathways were inactivated by 6G. To sum up, 6G protected hypoxia-stimulated PC-12 cells through miR-103-mediatated down-regulation of BNIP3 by inhibiting p38 MAPK and JNK pathways. Highlights 6-Gingerols (6G) is a promising agent for cerebral ischemia therapy. The neuroprotective effects of 6G are mediated by miR-103 and BNIP3. Up-regulation of miR-103 exerts neuroprotective effects.
寻找治疗脑缺血的新型治疗剂迫在眉睫。这些实验探索了 6-姜酚（6G）在缺氧刺激的大鼠 PC-12 细胞中的潜在作用。通过 MTT 测定法、流式细胞术测定法和 Western blot 分析分别研究细胞活力、细胞凋亡及其相关蛋白。此外，还说明了 6G 是否通过 miR-103 实现其在缺氧诱导损伤中的作用。此外，还研究了相关的信号通路。显然，缺氧处理会抑制细胞活力并增强细胞凋亡，而 6G 则可以改善这种趋势。然后我们观察到缺氧给药会增加 miR-103 的表达，而 6G 可以进一步增加缺氧刺激的 PC-12 细胞中 miR-103 的表达。miR-103 的抑制减弱了 6G 对缺氧处理的 PC-12 细胞的神经保护作用。此外，Bcl2/腺病毒 EIB 19kD 相互作用蛋白 3（BNIP3）是 miR-103 的靶标，BNIP3 的上调也减弱了 6G 对缺氧处理的 PC-12 细胞的神经保护作用。缺氧激活了 p38MAPK 和 JNK 通路，而 6G 则使其失活。总之，6G 通过 miR-103 介导的 BNIP3 下调，通过抑制 p38MAPK 和 JNK 通路来保护缺氧刺激的 PC-12 细胞。亮点 6-姜酚（6G）是治疗脑缺血的有前途的药物。6G 的神经保护作用是通过 miR-103 和 BNIP3 介导的。miR-103 的上调发挥神经保护作用。
