Multiparametric evaluation of the cytoprotective effect of the Mangifera indica L. stem bark extract and mangiferin in HepG2 cells

Author:

Tolosa Laia1,Rodeiro Idania2,Donato M Teresa134,Herrera José A5,Delgado René6,Castell José V134,Gómez-Lechón M José14

Affiliation:

1. Unidad de Hepatología Experimental, Centro de Investigación, Hospital La Fe, Valencia, Spain

2. Departamento de Farmacología, Centro de Bioproductos Marinos (CEBIMAR), La Habana, Cuba

3. Departamento de Bioquímica y Biología Molecular, Universidad de Valencia, Valencia, Spain

4. CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain

5. Universidad de la Habana, La Habana, Cuba

6. Departamento de Farmacología Centro de Investigaciones y Desarrollo de Medicamentos, (CIDEM), La Habana, Cuba

Abstract

Abstract Objective Mango (Mangifera indica L.) stem bark extract (MSBE) is a natural product with biological properties and mangiferin is the major component. This paper reported the evaluation of the protective effects of MSBE and mangiferin against the toxicity induced in HepG2 cells by tert-butyl hydroperoxide or amiodarone. Method Nuclear morphology, cell viability, intracellular calcium concentration and reactive oxygen species (ROS) production were measured by using a high-content screening multiparametric assay. Key findings MSBE and mangiferin produced no toxicity below 500 mg/ml doses. A marked recovery in cell viability, which was reduced by the toxicants, was observed in cells pre-exposed to MSBE or mangiferin at 5–100 mg/ml doses. We also explored the possible interaction of both products over P-glycoprotein (P-gp). MSBE and mangiferin above 100 mg/ml inhibited the activity of P-gp in HepG2 cells. Conclusions MSBE and mangiferin showed cytoprotective effects of against oxidative damage and mitochondrial toxicity induced by xenobiotics to human hepatic cells but it seemed that other constituents of the extract could contribute to MSBE protective properties. In addition, the drug efflux should be taken into account because of the inhibition of the P-gp function observed in those cells exposed to both natural products.

Funder

Spanish Ministry of Science

ALIVE Foundation

Spanish Ministry of Health

Spanish Ministry of Economy and Competitiveness

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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