6-Gingerols (6G) reduces hypoxia-induced PC-12 cells apoptosis and autophagy through regulation of miR-103/BNIP3.

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.