Mitochondrial Protection and Anti-inflammatory Effects Induced by Emodin in the Human Neuroblastoma SH-SY5Y Cells Exposed to Hydrogen Peroxide: Involvement of the AMPK/Nrf2 Signaling Pathway.

Abstract

Emodin (EM; 1,3,8-trihydroxy-6-methylanthracene-9,10-dione; C15H10O5) is an anthraquinone and exerts cytoprotective effects, as observed in both in vitro and in vivo experimental models. Mitochondrial dysfunction induced by reactive species plays a central role in the onset and progression of different human diseases. Thus, we have tested here whether a pretreatment (for 4h) with EM (at 40µM) would be able to promote mitochondrial protection in the human neuroblastoma SH-SY5Y cells exposed to the pro-oxidant agent hydrogen peroxide (H2O2). We found that the pretreatment with EM suppressed the effects of H2O2 on the activity of the mitochondrial complexes I and V, as well as on the production of adenosine triphosphate (ATP) and on the mitochondrial membrane potential (MMP). EM also prevented the H2O2-induced collapse in the tricarboxylic acid cycle (TCA) function. An anti-inflammatory role for EM was also observed in this experimental model, since this anthraquinone decreased the secretion of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) by the H2O2-challenged cells. Inhibition of the adenosine monophosphate-activated protein kinase (AMPK) or silencing of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) abolished the protection induced by EM in the H2O2-treated cells. Therefore, EM prevented the H2O2-induced mitochondrial dysfunction and pro-inflammatory state in the SH-SY5Y cells by an AMPK/Nrf2-dependent manner.