The neuroprotective effects of curcumin are associated with the regulation of the reciprocal function between autophagy and HIF-1α in cerebral ischemia-reperfusion injury

Abstract

Purpose

The beneficial, neuroprotective effects of curcumin against ischemia-reperfusion injury have been demonstrated. In the present study, whether curcumin exerts neuroprotective effects associated with the inhibition of autophagy and hypoxia inducible factor-1α (HIF-1α) was investigated.

Materials and methods

PC12 cellular model of oxygen glucose deprivation/reperfusion (OGD/R) has been developed to mimic cerebral ischemia-reperfusion injury. Cell viability was evaluated using the CellTiter 96^® AQueous One Solution Cell Proliferation Assay. Apoptosis was assessed using flow cytometry. The expression levels of HIF-1α and autophagy-associated proteins, LC3 and P62, were examined using Western blot. The autophagy flux was quantitatively estimated based on the number of autophagic compartments using fluorescence microscopy. In addition, 3-methyladenine (3-MA) was administered to PC12 cells to investigate how autophagy affects HIF-1α. Moreover, the inhibitory effects of HIF-1α on autophagy activation level were examined.

Results

In this study, curcumin decreased the death and apoptosis of cells, and inhibited autophagy and HIF-1α under OGD/R conditions, consistent with 3-MA treatment or HIF-1α downregulation. Moreover, inhibition of autophagy caused a decrease in HIF-1α, and the attenuation of HIF-1α induced autophagy suppression under OGD/R conditions.

Conclusion

The results of this study showed that curcumin exerts neuroprotective effects against ischemia-reperfusion, which is associated with the regulation of the reciprocal function between autophagy and HIF-1α.

Keywords:

• curcumin
• cerebral ischemia-reperfusion
• autophagy
• hypoxia inducible factor-1α

Acknowledgments

This study was supported by the National Natural Science Foundation of China (No 81771271), the Second Batch Basic Clinical Tight Integration Platform Project (No S208), and the project titled “Tanshinone IIA Regulates CD4⁺ Cell Differentiation in the Treatment of Multiple Sclerosis Diseases and Related Mechanisms” (No D255).

Disclosure

The authors report no conflicts of interest in this work.