Neuroprotective effect of α-mangostin and curcumin against iodoacetate-induced cell death

Abstract

Curcumin is a phenolic yellow curry pigment with anti-inflammatory and antioxidant activities and α-mangostin is a xanthone isolated from mangosteen fruit with antioxidant properties. Iodoacetate (IAA) is an inhibitor of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase that induces a model of metabolic inhibition in neurons where reactive oxygen species (ROS) production is a significant mechanism. Furthermore, it has been shown that the induction of heme oxygenase-1 (HO-1) protects against IAA-induced neuronal death.

Objectives

To study the effects of α-mangostin and curcumin against the IAA-induced cell death and on HO-1 expression in primary cultures of cerebellar granule neurons (CGNs).

Methods

CGNs were treated with curcumin or α-mangostin before the addition of IAA. Cell viability and ROS production were measured 24 and 4 hours after IAA addition, respectively. HO-1 expression was measured by western blot.

Results

Both α-mangostin and curcumin pretreatment ameliorated the neuronal death induced by IAA in a concentration-dependent way, which was associated with an amelioration of IAA-induced ROS formation. In addition, it was found that α-mangostin and curcumin induced HO-1 expression.

Discussion

Treatment with α-mangostin and curcumin provided a neuroprotective effect against IAA in primary cultures of CGNs, an effect associated with an amelioration of the IAA-induced ROS production. HO-1 induced by these antioxidants may also be involved in the neuroprotective effect. Future work will be required to determine whether α-mangostin may cross the blood–brain barrier and achieve enough bioavailability to elicit a protective response in the brain being an effective nutraceutical compound for preventive therapy of neurodegenerative diseases.

Keywords:

• Alpha-mangostin
• Cerebellar granule neurons
• Curcumin
• Heme oxygenase-1
• Reactive oxygen species

Acknowledgements

Laura María Reyes-Fermín and Susana González-Reyes contributed equally to this work. This work was supported by CONACyT (Consejo Nacional de Ciencia y Tecnología, México) grant 129838 and PAPIIT (DGAPA-UNAM) grant IN201910. We thank MVZ Atonatiu Gómez for continuous support with the rats. The authors report no conflicts of interest.