Maltol, a chemical isolated from ginseng root, has shown treatment effects on several pathological processes including osteoarthritis, diabetic peripheral neuropathy and liver fibrosis. Nevertheless, its effect on ischemia‑induced neuron death remains elusive. In the present study, the treatment effect of maltol on ischemia‑induced neuron damage was investigated by using oxygen and glucose deprivation (OGD) model in SH‑SY5Y cells. In vitro studies revealed that maltol protected SH‑SY5Y cells against OGD‑induced chromatinolysis by inhibiting two reactive oxygen species (ROS)‑regulated pathways. One was DNA double‑strand breaks and the other was nuclear translocation of apoptosis inducing factor. Mechanistically, maltol not only inhibited OGD‑induced depletion of glutathione and cysteine by maintaining cystine/glutamate antiporter (xCT) level, but also abrogated OGD‑induced catalase downregulation. Meanwhile, maltol also alleviated OGD‑induced inactivation of mTOR by attenuating OGD‑induced depletion of adenosine triphosphate and pyruvate and downregulation of pyruvate kinase M2, indicating that maltol inhibited the glycolysis dysfunction caused by OGD. Considering that activated mammalian target of the rapamycin (mTOR) could lead to enhanced xCT expression and decreased catalase degradation by autophagy, these findings indicated that maltol attenuated OGD‑induced ROS via inhibition of mTOR inactivation by maintaining pyruvate level. Taken together, it was demonstrated that maltol prevented OGD‑induced chromatinolysis in SH‑SY5Y cells via inhibiting pyruvate depletion.
Keywords: apoptosis inducing factor; chromatinolysis; glycolysis; maltol; oxygen glucose deprivation.