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Clinical pharmacology and translational medicine 2019

Protective Effects of Crude Plant Extracts against Aminochrome-induced toxicity in Human Astrocytoma Cells: Implications for Parkinson's Disease.

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Viviane Ngoungoure
Patricia Muñoz
Yousef Tizabi
Raul Valdes
Paul Moundipa
Juan Segura-Aguilar

Keywords

Abstract

Aminochrome, an endogenous compound formed during dopamine oxidation can induce neurotoxicity under certain aberrant conditions and induce Parkinson-like syndrome. Glutathione transferase M2 (GSTM2) activity of astrocytes by catalysing the conjugation of aminochrome with glutathione, can offer protection against aminochrome toxicity. Some medicinal toxicity through this plants may exert protective effect against aminochrome mechanism.

Methods
In the present study, extracts from plants native to Cameroon, such as Alchornea laxiflora (leaves), Dacryodes edulis (barks), Annona muricata (seeds), Annona senegalensis (barks) were evaluated for their protection against aminochrome-induced toxicity in human glioblastoma/ astrocytoma U373MG wild type and U373MGsiGT6 cells in which GSTM2 expression was 74% silenced. The cells were pre-incubated with the plant extracts for 2 hr before addition of aminochrome (75 μM) and measurement of cell death/viability by flow cytometry after 24 hr incubation.

Results
The extract of A. laxiflora (1 μg/ml), D. edulis (25 μg/ml), A. muricata (25 μg/ml) and A. senegalensis (25μg/ml) significantly decreased aminochrome-induced toxicity in U373siGST6 and U373MG cells. However, only A. laxiflora and A. muricata significantly increased the mitochondria membrane potential in U373siGST6 cells following aminochrome treatment.

The results indicate that extracts of some Cameroon plants can provide protection against aminochrome-induced toxicity and mitochondria dysfunction in human glioblastoma/astrocytoma cells. Although further identification of active components of these extracts is needed, potential usefulness of these compounds in Parkinson's disease may be suggested.

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