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Alpha-Mangostin Alleviates the Short-term 6-Hydroxydopamine-Induced Neurotoxicity and Oxidative Damage in Rat Cortical Slices and in Caenorhabditis elegans

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Abstract

The development, at the experimental level, of therapeutic strategies based on natural products to attenuate neurological alterations in degenerative disorders has gained attention. Antioxidant molecules exhibit both anti-inflammatory and neuroprotective properties. Alpha-mangostin (α-Man) is a natural xanthonoid isolated from the mangosteen tree with demonstrated antioxidant and cytoprotective properties. In this study, we investigated the antioxidant and protective properties of α-Man, both ex vivo and in vivo. We assessed the mitochondrial reductant capacity and oxidative damage to lipids in rat cortical slices, and several endpoints characteristic of physiological stress in the nematode, Caenorhabditis elegans (C. elegans), upon exposure to the parkinsonian neurotoxin, 6-hydroxydopamine (6-OHDA). In rat cortical slices, α-Man (25 and 50 µM) reduced the 6-OHDA (100 µM)-induced oxidative damage to lipid levels, but failed to reverse loss in cell viability. In wild-type (N2) C. elegans, α-Man (5–100 µM) protected against 6-OHDA (25 mM)-induced decrease in survival when administered either as pre- or post-treatment. Protective effects of α-Man were also observed on survival in the VC1772 strain (skn-1 KO−) exposed to 6-OHDA, though the extent of the protection was lesser than in the wild-type N2 strain. However, α-Man (5–50 µM) failed to attenuate the 6-OHDA-induced motor alterations in the N2 strain. The loss of lifespan induced by 6-OHDA in the N2 strain was fully reversed by high concentrations of α-Man. In addition, while 6-OHDA decreased the expression of glutathione S-transferase in the CL2166 C. elegans strain, α-Man preserved and stimulated the expression of this protein. α-Man (25 µM) also prevented 6-OHDA-induced dopaminergic neurodegeneration in the BZ555 C. elegans strain. Altogether, our novel results suggest that α-Man affords partial protection against several, but not all, short-term toxic effects induced by 6-OHDA in cortical slices and in a skn-1-dependent manner in C. elegans.

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Funding

MA was supported in part by the National Institutes of Health (NIEHS) grant numbers NIEHS R01ES07331 and R01ES10563.

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Authors and Affiliations

  1. Laboratorio de Aminoácidos Excitadores/Laboratorio de Neurofarmacología Molecular Y Nanotecnología, Instituto Nacional de Neurología Y Neurocirugía, Insurgentes Sur 3877, 14269, Mexico City, Mexico

    Rubén Estrada-Valencia, María Ester Hurtado-Díaz, Edgar Rangel-López & Abel Santamaría

  2. Facultad de Ciencias, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico

    Rubén Estrada-Valencia & María Ester Hurtado-Díaz

  3. Departamento de Biología de La Reproducción, Universidad Autónoma Metropolitana Campus Iztapalapa, 09340, Mexico City, Mexico

    Socorro Retana-Márquez

  4. Instituto de Investigaciones Biomédicas Maimonides de Córdoba (IMIBIC), Cordoba, Spain

    Isaac Túnez

  5. Departamento de Bioquímica Y Biología Molecular, Facultad de Medicina Y Enfermería, Universidad de Córdoba, Córdoba, Spain

    Isaac Túnez

  6. Red Española de Excelencia en Estimulación Cerebral (REDESTIM), Cordoba, Spain

    Isaac Túnez

  7. IM Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia

    Alexey Tinkov

  8. Cellular Stress Response and Signal Transduction Research Laboratory, Department of Medical Pharmacology, Faculty of Medicine, Gazi University, Beşevler, Ankara, Turkey

    Cimen Karasu

  9. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Beatriz Ferrer & Michael Aschner

  10. Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico

    José Pedraza-Chaverri

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  1. Rubén Estrada-Valencia
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  11. Abel Santamaría
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Correspondence to Michael Aschner or Abel Santamaría.

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Estrada-Valencia, R., Hurtado-Díaz, M.E., Rangel-López, E. et al. Alpha-Mangostin Alleviates the Short-term 6-Hydroxydopamine-Induced Neurotoxicity and Oxidative Damage in Rat Cortical Slices and in Caenorhabditis elegans. Neurotox Res 40, 573–584 (2022). https://doi.org/10.1007/s12640-022-00493-8

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