Oleuropein Aglycone Peracetylated (3,4-DHPEA-EA(P)) Attenuates H2O2-Mediated Cytotoxicity in C2C12 Myocytes via Inactivation of p-JNK/p-c-Jun Signaling Pathway

Monica Nardi; Sara Baldelli; Maria Rosa Ciriolo; Paola Costanzo; Antonio Procopio; Carmela Colica

doi:10.20944/preprints202007.0247.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 11 July 2020 / Approved: 12 July 2020 / Online: 12 July 2020 (08:22:31 CEST)

Oleuropein, glycosylated secoiridoid present in olive leaves is known to be an important antioxidant phenolic compound. We studied the antioxidant effect of low doses of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H2O2). Both compounds were used at a concentration of 10 μM and were able to inhibit cell death induced by the H2O2 treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions, H2O2 efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggests that the growth arrest and cell death of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects the myogenesis of C2C12 cells; because MyoD mRNA levels and the differentiation process are restored with 3,4-DHPEA-EA(P) after treatment. Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process in a genomic and epigenomic manner by functioning as an efficient antioxidant.

3,4-DHPEA-EA; C2C12 myocytes; olive oil; antioxidant; skeletal muscle

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Oleuropein Aglycone Peracetylated (3,4-DHPEA-EA(P)) Attenuates H₂O₂-Mediated Cytotoxicity in C2C12 Myocytes via Inactivation of p-JNK/p-c-Jun Signaling Pathway

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